Evidence Report/Technology Assessment 

Number 186 

Family History and Improving Health 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. HHSA 290-2007-10060-I

Prepared by: 

McMaster University Evidence-based Practice Center, Hamilton, ON 

Task Order Leaders: 

Nadeem Qureshi, M.B.B.S., M.Sc., M.R.C.G.P., D.M. 

Brenda Wilson, M.B., Ch.B., M.Sc., M.R.C.P.(U.K.), F.F.P.H. 

Pasqualina Santaguida, B.Sc., P.T., Ph.D. 

Authors: 

Nadeem Qureshi, M.B.B.S., M.Sc., M.R.C.G.P., D.M. 

Brenda Wilson, M.B., Ch.B., M.Sc., M.R.C.P.(U.K.), F.F.P.H. 

Pasqualina Santaguida, B.Sc., P.T., Ph.D. 

Julian Little, M.A., Ph.D. 

June Carroll, M.D., C.C.F.P., F.C.F.P. 

Judith Allanson, M.B., Ch.B., F.R.C.P., F.R.C.P.(C.), F.C.C.M.G., D.A.B.M.G. 

Parminder Raina, B.Sc. Ph.D. 

AHRQ Publication No. 09-E016 

August 2009
This report is based on research conducted by the McMaster University Evidence-based 

Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality 

(AHRQ), Rockville, MD (Contract No. HHSA 290-2007-10060-I). The findings and 

conclusions in this document are those of the authors, who are responsible for its content, 

and do not necessarily represent the views of AHRQ. No statement in this report should 

be construed as an official position of AHRQ or of the U.S. Department of Health and 

Human Services. 

The information in this report is intended to help clinicians, employers, policymakers, 

and others make informed decisions about the provision of health care services. This 

report is intended as a reference and not as a substitute for clinical judgment. 

This report may be used, in whole or in part, as the basis for the development of clinical 

practice guidelines and other quality enhancement tools, or as a basis for reimbursement 

and coverage policies. AHRQ or U.S. Department of Health and Human Services 

endorsement of such derivative products may not be stated or implied. 
This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

Qureshi N, Wilson B, Santaguida P, Little J, Carroll J, Allanson J, Raina P. NIH State-of-theScience Conference: Family History and Improving Health. Evidence Report/Technology 

Assessment No. 186. (Prepared by the McMaster University Evidence-based Practice Center, 

under Contract No. 290-2007-10060-I.) AHRQ Publication No. 09-E016. Rockville, MD: 

Agency for Healthcare Research and Quality. August 2009. 

No investigators have any affiliations or financial involvement (e.g., employment, consultancies, 

honoraria, stock options, expert testimony, grants or patents received or pending, or royalties) 

that conflict with material presented in this report. 

ii 
Preface 

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. The reports and assessments provide organizations 

with comprehensive, science-based information on common, costly medical conditions and new 

health care technologies. The EPCs systematically review the relevant scientific literature on 

topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments. 

To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

We welcome comments on this evidence report. They may be sent by mail to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, 

Rockville, MD 20850, or by e-mail to epc@ahrq.gov. 

Jean Slutsky, P.A., M.S.P.H. 

Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality

Carolyn M. Clancy, M.D. 

Director 

Agency for Healthcare Research and Quality 

Beth A. Collins Sharp, R.N., Ph.D. 

Director, EPC Program 

Agency for Healthcare Research and Quality 

Supriya Janakiraman, M.D., M.P.H. 

EPC Program Task Order Officer 

Agency for Healthcare Research and Quality 

Lata Nerurkar, Ph.D. 

Senior Advisor to the National Institutes of 

Health Consensus Development Program 

Barnett S. Kramer, M.D., M.P.H. 

Associate Director 

Office of Disease Prevention 

Officer of the Director

National Institutes of Health 

Jennifer Croswell, M.D. 

Acting Director 

National Institutes of Health Office of Medical 

Applications of Research 

iii 
Acknowledgments 

The researchers at the Evidence-based Practice Center would like to acknowledge the 

following people for their contributions. 

We are grateful to our Task Officer, Supriya Janakiraman and members of the technical 

expert panel, Al Berg (Panel Chair), Wylie Burke, Lisa Madlensky, and Louise Acheson who 

were instrumental in defining the parameters of this review. We would also like to acknowledge 

Gurvaneet Randhawa who was a member of the Technical Expert Panel and a peer reviewer. 

We would also like to thank those who worked so conscientiously, screening citations, 

abstracting data, preparing figures and editing the report: Carolyn Archer, Lynda Booker, 

Roxanne Cheeseman, Connie Freeborn, Jeffrey Freeborn, Lois Freeman-Collins, Mary Gauld, 

Homa Keshavarz, Jinhui Ma, Sandra McIsaac, Michelle Penta, Maureen Rice, Cecile Royer, 

Carolina Ruiz-Culebro, Catherine Salmon, Robert Stevens, Kate Walker, Rachel Morris, Laura 

Cross-Bardell, and Silvia Visentin. 

iv 
v 

Structured Abstract 

Objectives: This systematic review aimed to evaluate, within unselected populations: Question 1 

(Q1) key elements of family history (FH) which usefully predict subsequent disease; Question 2 

(Q2) the accuracy of reporting FH; Question 3 (Q3) the impact of FH-based risk information on 

the uptake of preventive interventions; Question 4 (Q4) the potential for harms associated with 

collecting cancer FH; Question 5 (Q5) factors that facilitate or hinder the collection of family 

history; and, Question 6 (Q6) future directions. 

Data Sources: MEDLINE®, EMBASE®, CINAHL®, Cochrane Controlled Trial Register®

(CCTR) ®, and PsycINFO were searched from 1995 to March 2, 2009 inclusive. 

Review Methods: Standard systematic review methodology was employed. Eligibility criteria 

varied by question, but overall, specified studies reported in English, excluded qualitative 

designs, and limited populations to those unselected for pre-existing risk (except for Q2). Study 

designs and outcomes varied by research question. 

Results: One hundred and thirty-seven publications were eligible in total for this review. Q1: 

Key elements of FH: Eighty-nine studies were eligible for this question of which 59 reported FH 

and data on subsequent or current disease in subjects. The varied definitions of positive FH were 

consistently associated with elevated relative risks, but their value in predicting future risk or 

detecting current disease was difficult to assess without considering further information on other 

risk factors or the available preventive interventions. Q2: Accuracy of FH Reporting. Thirtyseven studies evaluated accuracy and showed relatively high specificity and low sensitivity 

across all disease categories. Q3: Uptake of preventive interventions. Two studies evaluated the 

impact of FH-based risk and the evidence was insufficient to establish any effect on change in 

clinical preventive behavior or uptake of interventions. Q4: Harms of FH taking. Three studies 

evaluated the impact of FH-based risk information on psychological outcomes and indicated no 

evidence of significant harm.Q5: Factors affecting FH collection: The evidence base for 

addressing Q5 is heterogeneous and limited to six studies exploring the association between 

various factors and family history reporting, documentation and discussion.

Conclusions: Our review indicates: (Q1) Many FH definitions showed low discriminatory 

accuracy in predicting disease risk in individuals but further research is warranted; (Q2) accuracy 

of reporting is higher for relatives without, than those affected by, a given disease; (Q3) there is 

insufficient evidence to assess the effect of FH-based risk assessment on preventive behaviors; 

(Q4) there is limited evidence to assess whether the provision of FH-based personalized risk 

assessment results in adverse outcomes; (Q5) there is little evidence on factors affecting FH 

reporting and collection in primary care. 

Contents 

Executive Summary...........................................................................................................................1 

Evidence Report.............................................................................................................................11 

Chapter 1. Introduction ....................................................................................................................13 

Background...................................................................................................................................13 

Overall Evaluation Approach .......................................................................................................14 

Scope and Purpose of the Systematic Review..............................................................................14 

Chapter 2. Methods..........................................................................................................................17 

Analytic Framework ....................................................................................................................17 

Search Strategy .......................................................................................................................17 

Eligibility Criteria ....................................................................................................................19 

Eligibility Criteria for Research Q1 ........................................................................................19 

Eligibility Criteria for Research Q2.........................................................................................21 

Eligibility Criteria for Research Q3.........................................................................................22 

Eligibility Criteria for Research Q4.........................................................................................23 

Eligibility Criteria for Research Q5.........................................................................................25 

Study Selection ........................................................................................................................26 

Data Extraction ........................................................................................................................26 

Quality Assessment .................................................................................................................26 

Summarizing our Findings: Descriptive and Analytic Approaches ............................................27 

 Peer Review Process....................................................................................................................29 

Chapter 3. Results ............................................................................................................................31 

Question 1: What are the Key Elements of a Family History in a Primary Care Setting for the 

Purposes of Risk Assessment for Common Diseases? .................................................................32 

Introduction..............................................................................................................................32 

Note on Interpretation of Results.............................................................................................32 

Breast Cancer...........................................................................................................................33 

Colorectal Cancer.....................................................................................................................37 

Prostate Cancer ........................................................................................................................41 

Coronary Heart Disease ...........................................................................................................44 

Stroke .......................................................................................................................................47 

Diabetes....................................................................................................................................49 

Asthma and Atopic Disease.....................................................................................................55 

Mental Illness...........................................................................................................................60 

Question 2: What is the Accuracy of the Family History, and Under What Conditions Does the 

Accuracy Vary? ............................................................................................................................65 

General Approach to Evaluating Accuracy...............................................................................65 

Accuracy of Self-reporting of Cancer FH.................................................................................66 

Accuracy of Self-reporting of Mental Illness Disorder FH.......................................................80 

Schizophrenia and Related Disorders .......................................................................................82 

Dementia and Depression..........................................................................................................83 

vii 
Other Disorders of Mental Health ..............................................................................................84 

Accuracy of Self-reporting of Parkinson’s Disease FH..............................................................90 

Accuracy of Self-reporting of Diabetes FH ................................................................................92 

Accuracy of Self-reporting of Cardiovascular Diseases FH .......................................................92 

Question 3. What is the Direct Evidence That Routinely Getting a Family History Will Improve 

Health Outcomes for the Patient and/or Family?..........................................................................101 

General Approach .....................................................................................................................101 

Studies Reviewed ......................................................................................................................101 

Outcomes...................................................................................................................................102 

Quality Assessment of Studies..................................................................................................104 

Conclusion.................................................................................................................................105 

Question 4. What is the Direct Evidence That Routinely Getting a Family History Will Result in 

Adverse Outcomes for the Patient and/or Family?.......................................................................106 

General Approach .....................................................................................................................106 

Studies Reviewed ......................................................................................................................106 

Outcomes...................................................................................................................................107 

Quality Assessment of Studies..................................................................................................111 

Conclusion.................................................................................................................................111 

Question 5. What are the Factors That Encourage or Discourage Obtaining and Using a Family 

History?.........................................................................................................................................112 

 General Approach .....................................................................................................................112 

Studies Reviewed ......................................................................................................................112 

Outcomes...................................................................................................................................113 

Quality Assessment of Studies..................................................................................................115 

Conclusion.................................................................................................................................116 

Chapter 4. Discussion ......................................................................................................................117 

Overview ......................................................................................................................................117 

Q1. What are the Key Elements of a Family History in a Primary Care Setting for the Purposes 

of Risk Assessment for Common Diseases?..............................................................................117 

Q2. What is the Accuracy of the Family History, and Under What Conditions Does the Accuracy 

Vary?..........................................................................................................................................119 

Q3. What is the Direct Evidence That Routinely Getting a Family History Will Improve Health 

Outcomes for the Patient and/or Family? .................................................................................121 

Q4. What is the Direct Evidence That Routinely Getting a Family History Will Result in 

Adverse Outcomes for the Patient and/or Family?....................................................................121 

Q5. What are the Factors That Encourage or Discourage Obtaining and Using a Family 

History? .....................................................................................................................................122 

Limitations....................................................................................................................................123 

Conclusion....................................................................................................................................124 

Reference List ..................................................................................................................................129 

Tables 

Table 1. List of included and excluded outcomes by major disease categories ................................20 

Table 2. Notional classification of family history items and definition of a positive family history 28 

viii 
Table 3. Three-level risk stratification system..................................................................................50 

Table 4. Discriminatory accuracy metrics associated with risk stratification system ......................50 

Table 5. Accuracy of self-reporting of FH for cancer in studies that verified the status for breast 

cancer in relatives ...............................................................................................................69 

Table 6. Accuracy of self-reporting of FH for cancer in studies that verified the status for 

colorectal cancer in relatives...............................................................................................72

Table 7. Accuracy of self-reporting of FH for cancer in studies that verified the status for ovarian 

 cancer in relatives ...............................................................................................................75 

Table 8. Accuracy of self-reporting of FH for cancer in studies that verified the status for prostate 

cancer in relatives ...............................................................................................................77 

Table 9. Accuracy of self-reporting of FH for cancer in studies that verified the status for other 

cancers in relatives..............................................................................................................79 

Table 10. Accuracy of self-reporting of FH for relatives with mental illnesses ...............................86 

Table 11. Accuracy of self-reporting of FH for relatives with other diseases...................................95 

Table 12. Description of studies with evidence that routinely getting a FH will improve outcomes 

 for the patient and/or family ...........................................................................................103 

Table 13. Description of studies with evidence that routinely getting a FH will result in adverse 

 outcomes for the patient and/or family ............................................................................108 

Table 14. Findings from studies with evidence that routinely getting a FH will result in adverse 

 outcomes for the patient and/or family ............................................................................110 

Table 15. Factors associated with improved FH collection and utilization.....................................115 

Figures 

Figure 1. Analytic framework for the research questions evaluated in this review........................ 18 

Figure 2. Flow of studies through review ....................................................................................... 31 

Figure 3. Breast Cancer, Longitudinal Studies, Sensitivity............................................................ 35 

Figure 4. Breast Cancer, Longitudinal Studies, Specificity............................................................ 35 

Figure 5. Breast Cancer, Cross-sectional Studies, Sensitivity........................................................ 36 

Figure 6. Breast Cancer, Cross-sectional Studies, Specificity........................................................ 36 

Figure 7. CRC, Longitudinal Studies, Sensitivity........................................................................... 39 

Figure 8. CRC, Longitudinal Studies, Specificity .......................................................................... 39 

Figure 9. CRC, Cross-sectional Studies, Sensitivity ......................................................................40 

Figure 10. CRC, Cross-sectional Studies, Specificity ......................................................................40 

Figure 11. Prostate Cancer, Longitudinal Studies, Sensitivity .........................................................42 

Figure 12. Prostate Cancer, Longitudinal Studies, Specificity .........................................................42 

Figure 13. Prostate Cancer, Cross-sectional Studies, Sensitivity .....................................................43 

Figure 14. Prostate Cancer, Cross-sectional Studies, Specificity .....................................................43 

Figure 15. CHD, Longitudinal Studies, Sensitivity ..........................................................................45 

Figure 16. CHD, Longitudinal Studies, Specificity ..........................................................................45 

Figure 17. CHD, Cross-sectional Studies, Sensitivity ......................................................................46 

Figure 18. CHD, Cross-sectional Studies, Specificity.......................................................................46 

Figure 19. Stroke, Longitudinal Studies, Sensitivity ........................................................................48 

Figure 20. Stroke, Longitudinal Studies, Specificity ........................................................................48 

Figure 21. Diabetes, Longitudinal Studies, Sensitivity .....................................................................51 

Figure 22. Diabetes, Longitudinal Studies, Specificity ....................................................................52 

Figure 23. Diabetes, Cross-sectional Studies, Sensitivity .................................................................53 

ix 
x 

Figure 24. Diabetes, Cross-sectional Studies, Specificity .................................................................54 

Figure 25. Atopy, Longitudinal Studies, Sensitivity..........................................................................56 

Figure 26. Atopy, Longitudinal Studies, Specificity ........................................................................57 

Figure 27. Atopy, Cross-sectional Studies, Sensitivity ....................................................................57 

Figure 28. Atopy, Cross-sectional Studies, Specificity ....................................................................58 

Figure 29. Asthma, Longitudinal Studies, Sensitivity ......................................................................58 

Figure 30. Asthma, Longitudinal Studies, Specificity ......................................................................59 

Figure 31. Asthma, Cross-sectional Studies, Sensitivity ..................................................................59 

Figure 32. Asthma, Cross-sectional Studies, Specificity ..................................................................60 

Figure 33. MDD, Longitudinal Studies, Sensitivity .........................................................................62 

Figure 34. MDD, Longitudinal Studies, Specificity..........................................................................62 

Figure 35. MDD, Cross-sectional Studies, Sensitivity .....................................................................63 

Figure 36. MDD, Cross-sectional Studies, Specificity .....................................................................63 

Figure 37. Mood, Longitudinal Studies, Sensitivity .........................................................................64 

Figure 38. Mood, Longitudinal Studies, Specificity .........................................................................64 

Figure 39. A schematic representation of collecting FH (Index test) in typical manner (A) and in 

 persons with mental health disorders (B)(C) ....................................................................81 

Appendixes 

Appendix A: Search Strategies Detailed 

Appendix B: Forms 

Appendix C: Evidence Tables and Figures 

Appendix D: Excluded Studies 

Appendix E: Technical Expert Panel and Peer Reviewers 

Appendixes and Evidence Tables for this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/famhistimprov/famhimp.pdf. 
Executive Summary 

Background 

Family history (FH) represents the integration of shared genomic and environmental risk 

factors.1 First degree relatives (1DRs) share half their genomic information (roughly one copy of 

30-50,000 genes), and also behaviors, lifestyles, beliefs, culture, and physical environment, so 

their disease experience may offer a clue to shared susceptibilities. This suggests that a ‘low 

tech’ clinical approach–family history–might be a practical and useful way to target interventions 

and disease prevention efforts to those most at risk. There is empirical evidence to support the 

common observation that a positive FH confers an extra risk for many diseases: for example, 

detailed meta-analyses have convincingly demonstrated the association between having one or 

more 1DRs and risk of a number of common, complex disorders. However, appreciation that 

there is a link between FH and disease risk needs to be matched by evidence-based approaches to 

capturing and using such information in different clinical contexts. 

This systematic review attempts to address five key issues relevant to the practical value of 

systematically collecting FH information in primary care practice; what are the most useful 

elements of FH for assessing disease risk; can we be confident that individuals report FH for 

common diseases sufficiently and accurately; does systematic collection and use of FH 

information lead to positive health outcomes, and are there associated harms; what factors 

promote or hinder collecting and using FH information? 

The focus of this review is FH collection within the primary care context, where unselected 

populations present the full range of disease risks, where primary care practitioners undertake the 

activity, and where the goal is chronic disease risk assessment and prevention as an end in itself. 

Scope and Purpose of the Systematic Review 

This systematic review addresses five research questions (Q) relating to routine use of FH 

information in risk assessment for complex disorders, as follows: 

Q1. What are the key elements of a family history in a primary care setting for the purposes 

of risk assessment for common diseases? 

Q2. What is the accuracy of the family history, and under what conditions does the accuracy 

vary? 

Q3. What is the direct evidence that routinely getting a family history will improve health 

outcomes for the patient and/or family? 

Q4. What is the direct evidence that routinely getting a family history will result in adverse 

outcomes for the patient and/or family? 

Q5. What are the factors that encourage or discourage obtaining and using a family history? 

Research recommendations from each of these five questions were to be drawn together to 

answer Q6 in the conclusion. 

Q6. What are future research directions for assessing the value of family history for 

common diseases in the primary care setting? 

1 
Methods 

The five key research questions required interrogation across different domains of primary 

research literature. Therefore, standard systematic review methodology was employed, but 

eligibility criteria varied between questions. For all questions, these criteria were guided by 

discussion with the technical expert panel and partners. 

 Bibliographic databases searched for this review included: MEDLINE®, EMBASE®, 

CINAHL®, Cochrane Controlled Trial Register (CCTR)®, and PsycINFO. Years searched were 

1995 to March 2, 2009 inclusive. 

Eligibility criteria included English studies evaluating collection of FH for all diseases, with 

the exception of Q1 where we limited studies to those evaluating primary cancers (breast, 

colorectal, ovarian, prostate, and lung), cardiovascular diseases, mental health disorders, 

diabetes, asthma, and atopy. Interventions were defined as a structured/systematic collection of 

FH (Q1, 2, 3, and 4) or as correlates or factors facilitating or hindering the collection of FH (Q5). 

Populations were limited to those unselected for risk and typical for primary care settings with 

the exception of Q2. Study designs varied by research question; we excluded case control studies 

for Q1, observational studies for Q3 and Q4, and qualitative studies for all questions. The 

outcomes also varied with each research question and included disease incidence, metrics of 

accuracy, uptake of recommended preventive interventions, harms (e.g., psychological distress), 

and quality of FH collection. 

For research Q1, the analysis was aimed at comparing the discriminatory accuracy of 

different definitions of ‘positive’ FH, which might be used in routine clinical practice. 

Recognizing that the time and resources available for FH taking in these settings may be very 

limited, we developed a categorization of FH definitions to reflect the ‘complexity’ of the task 

(category A to E). It is important to note that this initial attempt at categorization is based on a 

notion of ‘likely effort required’, not on any a priori notion of the information value of the 

pedigree itself. Our rationale is that the FH definition which balances ‘adequate’ predictive 

validity with least effort (lowest category) might be the most likely to be useful in routine 

primary care settings. 

Results 

The search yielded 32,444 unique citations. During three levels of title and abstract 

screening, 31,190 articles were excluded. A total of 1,254 citations proceeded to full text 

screening. After the final eligibility screening, 137 publications were eligible for data extraction. 

Question 1. What are the Key Elements of a Family History in 

a Primary Care Setting for the Purposes of Risk Assessment 

for Common Diseases? 

Sixty-one reports of 59 studies were identified which met the eligibility criteria, reported FH 

definitions, and presented data which could be analyzed.2-62 In addition, one paper63 did not 

present data which could be included in the main analysis, but was descriptively summarized 

because the data were directly relevant to the research question. A further 17 papers64-80 were 

eligible but did not define FH, and 10 papers81-90 did not report interpretable data. These are 

2 
excluded from the results below. No studies addressing lung cancer or ovarian cancer were 

identified. 

Breast Cancer 

Two longitudinal,3,4 and two cross-sectional,5,6 studies were included. Four definitions of 

‘positive FH’ based on affected relatives were examined in five analyses. For the longitudinal 

analyses, the range of sensitivities was 0.06-0.26, and specificities 0.86- 0.95. The range of 

positive predictive values (PPVs) was 0.01-0.05, and negative predictive values (NPVs) 0.98-

0.99, for breast cancer prevalences up to 2.5 percent in the study samples. For the cross-sectional 

analyses, the sensitivities were 0.05 and 0.15, with corresponding specificities of 0.97 and 0.90. 

The PPVs were 0.01 and 0.09 and NPVs were 0.99 and 0.95, for prevalences of 0.7 and 5.4 

percent, respectively. 

Only a few discrete FH definitions were available for comparison, and there were too few 

data points to examine the area under the curve (AUC) from summary receiver operator 

characteristics (SROC) curves. The most sensitive FH marker for risk of future breast cancer 

appeared to be ‘at least one affected 1DR’. Conclusions regarding FH definitions used in a crosssectional (prevalence screening) approach are not possible because an insufficient number of 

studies were available with a range of definitions, although the rationale for FH in prevalence 

screening where other modalities exist is unclear. 

Colorectal Cancer 

One longitudinal analysis (based on two separate cohort studies),7 and two cross-sectional 

studies,8,9 were included. Four definitions of ‘positive FH’ were examined in multiple analyses, 

all focusing on 1DRs. The interpretation of the longitudinal analyses is limited because only one 

criterion for positive FH was used, (i.e., at least one affected 1DR). Sensitivities of 0.13 and 0.14 

were obtained for the male and female cohorts with a specificity of 0.92 for both. For both 

cohorts, the PPVs were 0.02 and the NPVs 0.99, for underlying colorectal cancer frequency in 

these two cohorts of approximately 1 percent. For the cross-sectional analyses, the range of 

sensitivities was 0.00 to 0.20, and specificities 0.88 to 1.00. The range of PPVs was 0.00 to 0.07 

and NPVs of 0.96 or higher, for overall colorectal cancer prevalences ranging from <1 to 4.5 

percent. The AUC for cross-sectional studies for category C FH definitions was 0.64.(based on 

one study). 

The results suggest that a simple definition of ‘positive FH’ (≥1 1DR) is the most sensitive 

for prediction, but if the underlying disease prevalence was similar to those populations studied, 

only 2 percent of people fulfilling this definition would actually go on to develop colorectal 

cancer (CRC) in the subsequent 16-20 years. The cross-sectional studies produced a range of 

sensitivities with similarly low PPVs for detecting current disease. The findings provide no 

definitive evidence of the superiority of one definition over any other for predicting future risk of 

colorectal cancer or assessing the likelihood of current disease. 

Prostate Cancer 

Four longitudinal,10-13 and two cross-sectional,14,15 studies were included. Ten discrete 

definitions of ‘positive FH’ were examined. For the longitudinal analyses, the range of 

3 
sensitivities was 0.00-0.21, and specificities 0.88-1.00. Omitting one study using mortality as the 

outcome, the range of PPVs was 0.11-0.26, and NPVs 0.92-1.00, for prostate cancer prevalences 

up to 8.7 percent. For the cross-sectional analyses, range of sensitivities was 0.01-0.26 and 

specificities 0.91-1.00. The PPVs were 0.02-0.14 and NPVs 0.96-0.98, for prostate cancer 

prevalences up to 8.7 percent. 

The majority of definitions available for analysis were based on 1DRs and, for longitudinal 

studies, the overall AUC for category B FH definitions was 0.51 and for category, C was 0.93. 

This suggests a step up in the overall accuracy of classification of future risk of prostate cancer 

when FH of 1DRs generally is taken into account compared with specifically parental or sibling 

history. It was not possible to calculate this metric for cross-sectional studies. The utility of using 

FH to predict risk of future prostate cancer or detect current disease depends on which of 

sensitivity, specificity, and overall classification accuracy would be prioritized in routine 

practice. 

Coronary Heart Disease 

 Five longitudinal,16-20 and three cross-sectional,21-23 studies were included. Seventeen 

discrete definitions of ‘positive FH’ were analyzed. For the longitudinal analyses, the range of 

sensitivities was 0.03-0.51 and specificities 0.66-0.98. The range of PPVs was 0-0.13 and NPVs 

0.66-0.98, for coronary heart disease (CHD) prevalences up to 10.4 percent. For the crosssectional analyses, the range of sensitivities was 0.07-0.70 and specificities 0.53-0.98. The range 

of PPVs was 0.08-0.31, and NPVs 0.83-0.98, for CHD prevalences up to 20.7 percent. 

Generally speaking, the highest sensitivities for prediction of future CHD risk were observed 

for the FH definition, ‘at least one affected parent’, although these also had lower specificities 

than other FH definitions. For category B FH definitions, the AUC was 0.57. For the assessment 

of possible current disease, the definition ‘at least one affected 1DR’ had a sensitivity of 70 

percent, but it was derived from a single study in which the knowledge of disease status may 

have influenced awareness of FH. The findings are not sufficiently definitive to indicate a 

specific FH definition as the most efficient for screening or prediction of future CHD, but 

provide the foundation for considering how to approach such analyses. 

Stroke 

Three longitudinal studies24-26 were included, allowing examination of three separate 

definitions of ‘positive FH’, all relating to parental illness. The range of sensitivities was 0.05-

0.33, and specificities 0.71-0.98. The range of PPVs was 0.0.02-0.08 and NPVs 0.96-0.98, for 

prevalences of stroke up to 3.9 percent. There were no cross-sectional studies. 

Many of the analyses were derived from one study,25 and do not provide definitive evidence 

for the utility of any particular FH definition for predicting the risk of stroke in the future. The 

AUC for these category B FH definitions was 0.43. 

Diabetes 

Five longitudinal,27-31 and 12 cross-sectional,32-43 studies were included, along with the 

findings of a cross-sectional study63 designed to examine different FH definitions but which did 

not have analyzable data. Twenty different definitions of ‘positive FH’ were analyzed. 

4 
For the longitudinal analyses, the range of sensitivities was 0.02-0.47, and specificities 0.79-

1.0. The range of PPVs was 0.02-0.38, and NPVs 0.86-0.99, for underlying diabetes prevalences 

up to 16.2 percent. For the cross-sectional analyses, the range of sensitivities was 0.02-0.83 and 

specificities 0.44-0.99, for prevalences up to 17.4 percent. One cross-sectional study63 reported 

the results of applying a three-level, FH-based, risk stratification system to representative U.S. 

adult survey data, where the overall diabetes prevalence was approximately 6.6 percent. Three 

FH definitions were applied, with sensitivities of 0.19-0.48 and specificities of 0.70-0.94. PPVs 

were 0.05-0.15 and NPVs were 0.95-0.98. 

Overall, category C FH definitions for prediction of future disease risk (≥1 affected 1DR) 

had an AUC 0.43. The cross-sectional analyses examined a wide range of definitions, but many 

were assessed within the same study. Some of the highest sensitivities in the review were 

observed for the cross-sectional diabetes data, although the expected trade-off with specificity 

was also noted. The AUC figures for category B, C, and D FH definitions were similar (0.69, 

0.71, and 0.64, respectively) suggesting no useful step up in discriminatory accuracy with 

extension of FH enquiry beyond 1DRs.. If the findings were replicated in further studies, they 

might suggest utility in using simple FH markers in preliminary triaging for diabetes screening. 

Asthma and Atopic Disease 

 Sixteen studies (17 publications) were included, four longitudinal,44-46,48 eleven crosssectional,2,49-58 and one59 which was treated as cross-sectional, presenting a followup analysis of 

a random sample of another eligible study.58 Four studies45,46,48,57 were relevant to atopic disease 

alone, ten2,49,51-56,58,59 to asthma alone, and two44,52 presented analyses for both asthma and atopic 

disease. Ten separate definitions of ‘positive FH’ were analyzed. 

For the longitudinal analyses of atopy, the range of sensitivities was 0.15-0.64, and 

specificities 0.44-0.91. The range of PPVs was 0.25-0.46 and NPVs 0.7-0.84, for atopy 

prevalences up to 38.6 percent. For the cross-sectional analyses of atopy, the range of 

sensitivities was 0.23-0.48, and specificities 0.56-0.83. The range of PPVs was 0.28-0.52 and 

NPVs 0.68-0.74, for atopic disease prevalences up to 36.2 percent. 

For the longitudinal asthma analyses, the range of sensitivities was 0.18-0.69 and 

specificities 0.43-0.91. The range of PPVs was 0.17-0.25 and NPVs 0.86-0.89, for an asthma 

prevalence of 14.8 percent. For the cross-sectional analyses, the range of sensitivities was 0.04-

0.76 and specificities 0.46-0.99. For the childhood studies only, the range of PPVs was 0.08-0.51 

and NPVs 0.82-0.92, for asthma prevalence up to 19.8 percent. For the two adult studies, the 

PPVs were 0.07, 0.13, and NPVs 0.96 and 0.98, respectively, for prevalences of asthma of 3.1 

and 5.5 percent. 

The longitudinal and cross-sectional atopy studies did not have sufficient independent data to 

undertake an AUC analysis. The longitudinal asthma analyses also focused on early childhood 

onset, and were all based on a single study. There seemed to be a clear increase in sensitivity 

with looser definition of FH, and a concomitant reduction in specificity, but the discriminatory 

accuracy was poor (AUC of 0.56). For the cross-sectional studies, category B FH definitions had 

AUCs of 0.73 (father had asthma) to 0.78 (mother had asthma) and category C definitions had an 

AUC of 0.67, suggesting that identifying disease in one parent provides maximum predictive 

information. For both disease outcomes (asthma and atopy), the cross-sectional studies were 

potentially subject to differential reporting of FH according to awareness of disease status. 

 

5 
Mental Illness 

One longitudinal,60 and one cross-sectional,62 study were included. Both examined outcomes 

to 26 years of age, and presented data on prediction of major depressive disorder (MDD); one 

study60 also examined the mood disorder as an outcome condition, considered a more appropriate 

measure in childhood and adolescence. The longitudinal study60 followed up the third generation 

of a family study in which the grandparents of the participants formed the inception cohort. Four 

definitions of ‘positive FH’ were examined. 

For the longitudinal analyses of MDD, the range of sensitivities was 0.72-0.83 and 

specificities 0.40-0.59; for mood disorder, the range of sensitivities was 0.73-0.83 and 

specificities 0.42-0.63. The range of PPVs for MDD was 0.14-0.18 and NPVs 0.92-0.95; for 

mood disorder, the corresponding metrics were 0.24-0.31 and 0.89-0.92. The overall prevalence 

of MDD for this study was 11.2 percent, and of mood disorder was 18.6 percent. A relatively 

high proportion of participants met at least one of the definitions for positive FH (44.1-62.7 

percent), reflecting the constitution of the original cohort. 

The cross-sectional analyses produced sensitivities of 0.12 and 0.24 and specificities of 0.85 

and 0.96, respectively. The PPVs were 0.33 and 0.45, and NPVs were 0.79 and 0.78, 

respectively, for a prevalence of MDD of 23.2 percent. 

For prediction of MDD and mood disorders up to early adulthood, all three FH definitions 

produced sensitivities at the high end of the range observed in this review. They were derived 

from a single study and their applicability to routine primary care practice is unclear. For the 

cross-sectional study, only two FH definitions were examined, and no definitive conclusions can 

be drawn regarding the utility of either for screening for underlying MDD. It was not possible to 

calculate AUC for any of this data. 

Question 2. What is the Accuracy of the Family History, and 

Under What Conditions Does the Accuracy Vary? 

A total of 37 publications evaluated the accuracy of reporting FH and were eligible for data 

extraction. There were 16 studies that evaluated accuracy of reporting cancer FH. These studies 

recruited probands with breast cancer,91-94 colorectal cancer,95-97 prostate cancer,98,99 ovarian 

cancer,100 mixed cancers (breast, ovarian, colorectal),101,102 Ewing’s Sarcoma,103 lymphoma,104

melanoma,105 and unspecified cancer.106 Subjects were recruited predominately from specialized 

settings or cancer registries, which would suggest high risk of spectrum and selection bias. 

Twelve studies evaluated accuracy in persons with mental health disorders that included persons 

with Schizophrenia,107-109 persons with dementia or depression,110-113 and mixed disorders.114-117

Nine studies evaluated other diseases that included Parkinson’s disease,118-120 diabetes,121-124

hypertension,121,123,125-127 and other cardiovascular disease.123-125,128 One study collected family 

history but reported only on the accuracy of informant age of onset rather than accuracy of 

disease status in the relatives; as such the results were not extracted for our research question.118

The methods for FH collection varied across studies as did the questions or tools used to 

collect FH. Some used highly standardized instruments and others used dichotomous probing 

(presence or absence of disease in any relative). Methods used to verify relatives’ disease status 

were primarily multimodal (medical records, disease or death registry, contact with relative) and 

relatives for whom verification could not be obtained were excluded from analyses. 

6 
Most studies probed the accuracy of reporting the same disease as that within the proband/ 

informant, but some studies probed a variety of disease outcomes, for example any cancer or any 

mental health disorder. Overall, specificity across all disease types and with varying modes of 

FH collection was consistently high. Sensitivities were lower and generally more variable 

depending on the disease outcome. Some of the mental health disorders showed the lowest 

sensitivities, breast cancer, and cardiovascular disease showed the highest values. 

Several studies evaluated predictors of accuracy in reporting FH. Factors related to the 

proband/informant includes age, gender, disease status, education level, race, marital status, type 

of disease, setting, and insurance status. Predictive factors associated with the relatives include, 

degree of relation, type of 1DR, disease subgroup, age, gender, and time since diagnosis. No 

clear trend emerged with age, gender, or education level of the informants and their impact on 

accuracy. No clear pattern across diseases emerges with the exception that there was a consistent 

trend towards increased accuracy of reporting relating to 1DRs compared to 2DRs or 3DRs; 

however, the majority of studies evaluated only 1DRs. Overall, these 37 studies had a high risk 

of spectrum bias (populations highly selected and not reflective of primary care), verification 

bias (different methods used inconsistently), and masking bias which may cause an 

overestimation of accuracy. 

Question 3. What is the Direct Evidence That Routinely 

Getting a Family History Will Improve Health Outcomes for 

the Patient and/or Family? 

We selected studies that identified the impact on health related outcomes of systematic 

collection of FH in a typical, non-selected primary care/general population. Only two studies 

were identified after full text review.129,130 Both studies were uncontrolled before-after designs 

and focused on breast cancer risk assessment, including FH collection, as the target intervention. 

In both studies, there was limited improvement in the clinically relevant process measure of 

mammography screening. In one study129 mammography screening improved from 76 to 93 

percent, however, the matched sample was small (n=29) and the change in screening did not 

reach statistical significance (p=0.057). There was no differentiation of the improvement in 

breast screening habits between the different risk strata. In the second study there was also 

limited improvement in adherence to mammography in all women (p=0.796) and for each age 

group (40-49; >=50 years old). Further, in women with high breast cancer risk (relative risk 

>=1.7) the adherence fell from 81 percent (17/21) to 71 percent (15/21), although this did not 

reach statistical significance (p<0.317). Both studies also demonstrated improvements in 

adherence to other process measures: breast self exam (BSE) and clinical breast exam (CBE). 

Both studies were at risk of selection bias sufficient to affect the interpretation of the results. 

Question 4. What is the Direct Evidence That Routinely 

Getting a Family History Will Result in Adverse Outcomes for 

the Patient and/or Family? 

Three studies met all eligibility criteria.131-133 These comprised a randomized controlled trial 

133and two uncontrolled before after studies.131,132 Each of studies recruited patients from single 

7 
British primary care office network with the number of respondents recruited varying and 

response rates of 19, 29, and 64 percent respectively. The proportion of recruited patients 

completing survey items at all time points was 91, 89, and 76 percent respectively. These studies 

suggest that structured FH collection and feedback of familial risk information had no 

deleterious psychological effects on patients at 6 to 12 weeks after FH intervention. One study131

further identified the relationship between breast cancer familial risk status and psychological 

impact. As well as having no deleterious psychological effect in any of the risk groups, for 

women who were at or just above average risk, the FH risk assessment may have led to 

appropriate reductions in perceived risk. 

Question 5. What are the Factors That Encourage or 

Discourage Obtaining and Using a Family History? 

Six studies were identified, four of which were undertaken in primary care offices.134-137 The 

other two studies’ populations were derived from patients being screened in the general 

population.138,139 Four studies were cross-sectional.135,136,138,139 The remaining two studies were a 

direct observational study137 and a prospective cohort study with a baseline cross-sectional 

survey.134 Factors associated with FH collection or discussion were the primary outcomes of 

interest of three studies.136,137,139 These data were retrieved in the other three studies from sub 

analyses presented in these publications.134,135,138 Two studies only recruited female 

patients.136,138 The identified outcomes of interest were: FH documented in medical records;134,136

FH discussed by doctor, either confirmed by direct observation137 or patient survey;135,138 and 

self reported FH.136,139 Women appeared to be better informants than men were and younger 

physicians were more enthusiastic about discussing FH. There were disparities in FH collection 

and reporting in underserved groups, specifically non-white ethic groups,136,139 those with lower 

educational status,139 and those on state health insurance.137

The evidence base for addressing Q5 is heterogeneous and limited to six studies exploring 

the association between various factors and FH reporting, documentation and discussion. In most 

studies the nature of the FH discussed or reported was not clearly identified, often just reported 

as dichotomous variables. Representativeness of these surveys is also limited by response bias 

and recall bias. Collectively, these issues limit the generalizability of the study findings, hence 

caution should be observed in applying this information to clinical situations in primary care.

Discussion and Conclusions 

This review was designed to inform a broad range of questions which ultimately address the 

clinical value of using FH in chronic disease risk assessment and prevention. The findings from 

studies reviewed in Q1, Q2, and Q5 should inform the nature and content of future FH tools, 

which should be developed according to the context in which the tools are being applied. A tool 

used for an initial general FH screening enquiry, such as during a new patient intake visit or 

routine physical examination, would generally be less focused than one developed for a specific 

purpose, such as identifying possible familial risk in a woman concerned because of a breast 

cancer diagnosis in a sibling. The starting point should be clarifying the minimal FH dataset 

necessary for each purpose, taking account of the evidence for accuracy, recall, and relevance of 

each piece of information. 

8 
1. Very few studies were designed to address Q1 directly, and the metrics reported usually 

related to strength of association between FH and disease incidence or prevalence rather than 

discriminatory ability when applied to individual patients. Our analyses were based largely on a 

re-examination of data generated for other research purposes. In most cases, positive FH, 

however defined, had no more than modest ability to correctly classify future risk of complex 

disorders in individuals. This is logical, because, by definition, they are not high penetrance 

single gene disorders. The required level of predictive accuracy depends on the purpose of the 

FH assessment, and the benefits, risks, and costs of decisions made based on the risk assessment. 

In principle, the definition of ‘positive FH’ which combines adequate predictive accuracy with 

the least effort to obtain it would be most suited to busy primary care settings. 

Recommendations for direction of future research: 

• Further clarification of the purpose of FH taking in primary care settings is required, 

so that future assessments of the utility of FH are based on an appreciation of the 

level of predictive accuracy that is required for the specific situation. 

• The evidence base requires studies designed explicitly for the purpose of examining 

the predictive ability of different ‘minimum’ FH definitions. This requires adequately 

powered, longitudinally designed studies in which detailed, extensive, clearly defined 

and documented FH components comprise the ‘exposures’, in which participants are 

followed up for a period which is clinically meaningful, in which adequate measures 

are taken to control bias, and in which the primary metrics relate to individual risk 

prediction. 

• FH items should be formally examined alongside other recommended or readily 

accessible risk factors, in order to identify the extent to which they provide (or need 

to provide) useful independent and/or incremental discriminatory ability. 

2. The accuracy of self reported FH has implications for the correct risk assessment and 

management of patients. Accurate reporting of the absence of disease (specificity) appears to be 

more common than accurate reporting of presence of disease (sensitivity) across different disease 

areas. Estimates of sensitivity show greater variation and the magnitude varies with different 

diseases. Although, there is limited evidence, accuracy of recall and reporting may be influenced 

by both patient and informant (relative) factors, and by the method used to collect FH. Accuracy 

of FH reporting may also be dependent on the method of collection, which is related to the 

disease area however, further evaluation is needed. 

Recommendations for direction of future research: 

• Future studies in accuracy should be undertaken in populations reflective of the 

primary care setting and representative of the spectrum of disease risk. 

• Future studies should endeavor to better characterize the attributes of the 

informant/proband and especially the relatives; the potential of these factors to 

influence the accuracy of reporting should be consistently evaluated. Future 

evaluation should be undertaken in the areas of asthma and atopy, affective mental 

health disorders, cardiovascular diseases, and diabetes. 

3. Within primary care populations, there is very limited evidence to support or refute the 

effect on risk-reducing behavior changes of taking a FH and using it to personalize risk of 

developing respective conditions. 

Recommendations for future research: 

9 
10 

• Well designed trials are required that compare the impact of FH-based, personalized 

risk advice with standard of care on risk reducing behaviors in populations at 

different risk levels (including population risk). The outcomes of interest need to be 

clinically relevant, either leading to improved mortality or morbidity or surrogate 

measures with strong evidence of links to improved health outcomes. Concurrent 

qualitative studies should also be considered. 

• Proposed trials should be based on evidence from systematic reviews to ensure that 

prescribed risk-reducing behaviors are evidence-based. 

4. In primary care populations, there is very limited information to evaluate direct harm 

incurred from the routine practice of taking FH and using it to personalize risk information. 

Recommendations for future research: 

• Trials of FH taking as an intervention should include capture of data to examine the 

full range of potential impacts on individuals of FH collection and implementation 

strategies based on familial risk identification, both negative and positive. Concurrent 

qualitative studies should also be considered. Baseline data on psychological status 

should be captured so that this can formally be adapted for use in outcome analyses. 

To enable appropriate evaluation of psychological harm, context-specific measures 

need to be developed and validated. 

 

5. In order to assess the content validity of systematic FH tools we need to know not only 

the factors that affect the recall of FH (Q2) but also those factors that affect the collection and 

use of FH. Thus far, there is limited information on collection and discussion of FH in primary 

care, with no factors identified that are associated with the use of the FH. There is some 

suggestion that populations from underserved communities are less likely to report and have the 

opportunity to discuss FH, but the level of evidence is weak. 

Recommendations for future research: 

• Further research is required to clarify the most important patient and practitioner 

factors that may affect the collection and use of FH. This likely requires the 

development of theoretical frameworks to guide appropriate design, and to ensure that 

methodologies adequately address the many potential biases and interactions between 

factors which may be encountered. The most important studies are those that address 

factors directly relevant to primary care practice, including highlighting patient 

factors which promote inequity in the application of effective interventions 

• Where inequities are identified, interventions should be designed to ameliorate these 

factors in future trials and service provision. Such research could include analyses of 

national population and practitioner survey databases. 

• While research should focus on clinically relevant outcomes, it should also include 

process evaluations to identify factors that affect the successful implementation of the 

FH interventions. 
Evidence Report 

 
 
 

Chapter 1. Introduction 

Background 

According to the Centers for Disease Control and Prevention, almost half of Americans live 

with at least one chronic condition, and chronic diseases account for 70 percent of all deaths in 

the United States, one third of potential years of life lost before 65, and three quarters of medical 

care costs.140 Although the role of important risk factors such tobacco, nutrition, and physical 

activity are well known, there are many unknown factors that contribute to risk and which 

prevent completely accurate individualized risk assessment across a range of diseases. 

Nevertheless, it is possible that a traditional, ‘low tech’ approach to risk assessment–family 

history–might be practical and useful for widespread application, to assist in identifying 

particular risks carried by individuals, in order to target interventions and efforts on disease 

prevention. Family history (FH) represents the integration of shared genomic and environmental 

risk factors.1 First degree relatives (1DRs) share half their genomic information (roughly one 

copy of 30-50,000 genes), and so their disease experience may offer a clue to shared 

susceptibilities, even in the absence of a complete understanding of the molecular etiology of a 

given condition. While FH assessment is a core approach in clinical genetics, FH may offer 

much more than the possibility of identifying relatively rare inherited diseases which follow a 

Mendelian inheritance pattern. Approached as a ‘black box’ FH may provide information on the 

influence of genetic variants which, collectively, act to increase or decrease disease 

susceptibility, and on other familial factors which alter risk (such as shared behaviors and 

lifestyles). 

Family history may therefore be a cost effective way of tapping into ‘integrated’ disease risk 

information.141 For most common chronic diseases, the impact of a positive FH has been 

recognized. For example, a population-based study in Utah observed that 14 percent of families 

accounted for 72 percent of the premature coronary heart disease (CHD) in the state, and 11 

percent of families accounted for 86 percent of premature cerebrovascular disease;142 in another 

study 30 percent of middle-aged British men who report a FH of CHD experience a 71 percent 

excess risk of CHD themselves over 10 years.143 Further, we are aware of the individual roles 

of obesity and FH in predicting the development of diabetes, but in combination, the predictive 

value increases from around 20 to 40 percent. 

Support for this approach also comes from a detailed meta-analysis,144 in which the 

association between having one or more 1DRs and risk of a number of common, complex 

disorders was convincingly demonstrated. 

However, there are important issues that need to be addressed regarding the overall utility of 

using FH information in primary care settings. The first issue relates to the capture of FH 

information in itself. For FH information to be useful, there should be some confidence that 

patients are able to report it accurately and consistently. This has been addressed for some 

cancers in a previous review.145 Secondly, there should be evidence that health professionals in 

primary care can capture such information accurately. Previous reviews145,146 have examined FH 

tools and demonstrated that the systematic use of a FH tool improves accuracy and completeness 

 

Appendixes and Evidence Tables for this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/famhistimprov/famhimp.pdf.

13 
of information capture. It appears that the crucial issue is use of a tool, rather than its specific 

format, although further research may clarify whether any particular attributes (such as patientcompleted versus professional-completed, or electronic versus paper) offer specific advantages 

for use in particular settings. An important issue which needs to be addressed is the ‘minimum 

FH dataset’ necessary for application in primary care settings for chronic disease risk 

prediction.147-151 It is important to bear in mind that primary care practitioners face constraints in 

relation to capturing FH information,152 and cannot necessarily replicate the practice of genetics 

specialists in completing detailed, three generational pedigrees. 

A broader, but crucial question is that of the overall benefits and harms of capturing FH 

information. Like any health care intervention, FH-based risk assessment carries resource 

implications and opportunity costs. Thus, its impact on health outcomes, both beneficial and 

harmful, should be assessed objectively in order to promote evidence-informed practice and 

policy. 

Overall Evaluation Approach 

In approaching these questions, we have borrowed from a range of evaluative frameworks 

including: methods developed in diagnostic and screening test research (applied to assessing 

individual FH items for their predictive validity, and for the assessment of accuracy of FH 

reporting): methods for the assessment of the effectiveness and safety of clinical interventions 

(applied to FH taking as a deliberate clinical intervention); and classical epidemiological 

methods (applied to the assessment of factors which promote or hinder FH taking as a routine 

clinical activity). 

Scope and Purpose of the Systematic Review 

This systematic review addresses six research questions relating to the analytic validity, the 

clinical validity, and the clinical utility of routinely using FH information in risk assessment for 

complex disorders, as follows. 

1. What are the key elements of a family history in a primary care setting for the purposes 

of risk assessment for common diseases? 

2. What is the accuracy of the family history, and under what conditions does the accuracy 

vary? 

3. What is the direct evidence that routinely getting a family history will improve health 

outcomes for the patient and/or family? 

4. What is the direct evidence that routinely getting a family history will result in adverse 

outcomes for the patient and/or family? 

5. What are the factors that encourage or discourage obtaining and using a family history? 

6. What are future research directions for assessing the value of family history for common 

diseases in the primary care setting? 

Regarding research question 1, the specific disease categories of interest were: 

• breast, ovarian, colorectal, prostate, and lung cancers 

• cardiovascular and heart disease 

• stroke 

• diabetes 

14 
15 

• asthma and allergies (atopic disease) 

• major depression and mood disorders 

in addition, key elements for consideration were information relating to: 

• ancestry 

• number of affected or unaffected relatives 

• lineage 

• age of onset 

• sex or gender 

• relationship (first degree, second degree) 

Question 6 is addressed by drawing together the evidence from questions 1 to 5 and therefore 

is not evaluated separately. The focus of this review is on using FH in primary care contexts, and 

as an intervention mainly for chronic disease risk assessment in large population groups, not 

assessment of rare genetic disorders in high risk groups. This has driven the eligibility criteria for 

studies towards: 

• study populations with the range of disease risk seen in primary care and general settings 

• study settings where primary care providers such as family physicians, internists, nurse 

practitioners, and obstetricians are taking family histories and assessing risk 

• family history taking as an intervention carried out by primary care practitioners and 

directed primarily towards chronic disease risk assessment and prevention as an end in 

itself 

• chronic disease prevention interventions evaluated in primary care or general populations 

with an inherent range of disease risks, but not selected because of special high risk 

(genetic or otherwise) 

The focus on study populations “unselected” for high risk implies groups of participants, 

which represent a full range of risks, potentially from very low to very high, by definition with 

clustering around an “average” value. These populations reflect the context of professional and 

patient decision-making in primary care - patients with a wide range of risks are encountered, but 

most are neither particularly high nor particularly low risk. This situation is distinguished from 

that where patients and their providers already have reason to suspect high disease risk, as such 

populations are more homogenous and are designed to exclude individuals who are likely to be 

average and low risk. While findings from ‘unselected’ populations may possibly be applicable 

to high risk groups, the converse cannot be assumed. 

Family history taking is a health care intervention and its evaluation requires as much 

attention to potential bias as any other intervention. An important potential confounder in 

assessing this intervention is pre-existing awareness of family illness. Living with a serious 

disease within a family can influence risk perceptions and health behaviors,153,154 quite 

independently of any intervention by a health professional. This means that the effect of FH 

taking as a deliberate clinical activity can only be meaningfully assessed using well-designed 

studies that can address confounding and bias. Family history taking is also an inherently 

complex intervention and needs to be separated from other activities, such as genetic testing. 

 

Chapter 2. Methods 

Analytic Framework 

The analytic framework is a schematic representation of the strategy for showing the 

relationships between the primary exposure, which is the collection of family history (FH), and 

the outcomes of interest for each research question (Q). Figure 1 shows the inter-relationships 

among the six research questions being addressed in this systematic review. 

The framework shows the logical connection between the research questions, commencing 

with the accuracy of clients reporting their family history (FH) (Q2). If we consider a key 

purpose for collecting family history, as a test to screen or identifying clients who might be at an 

altered risk for developing the same disease, then the selection of the optimal items that will 

comprise a comprehensive FH should be considered; evaluation of the evidence for those items 

that are most predictive of subsequent disease development is sought in (Q1). Evaluation of the 

evidence for the impact of collecting FH is addressed in the third research question (Q3). The 

potential for harmful outcomes as a result of collecting FH will also be addressed (Q4). 

The context in which FH is collected and factors that may facilitate or hinder its collection 

also have bearing on the validity of collecting FH (Q5). These contextual factors (Q5) and those 

related to accuracy of reporting (Q2) may influence the optimal selection of items to be included 

within a set constituting adequate FH collection for risk assessment in a primary care setting 

(Q1). Following the systematic collection of FH in a population representative of primary care, 

the uptake of prevention, screening, and other interventions are important outcomes of benefit 

that may result. The strength of the evidence from studies addressing Q1 through Q5 will inform 

future directions for assessing the value of FH on common chronic diseases in the primary care 

setting (Q6). 

Search Strategy 

Bibliographic databases searched for this review included: MEDLINE®, EMBASE®, 

CINAHL®, Cochrane Controlled Trials Register (CCTR)®, and PsycINFO. Years searched were 

1995 to March 2, 2009 inclusive. Our broad based search was not restricted by disease type, and 

yielded a very large number of titles and abstracts; as such, we limited the search to 1995 

forward. Detailed search strategies are listed in Appendix A. We reviewed a limited number of 

grey literature sites, including NCPEQ and the Center for Disease Control (CDC). In addition, 

we retrieved and evaluated references from eligible studies that were not captured in our search. 

Hand searching was not undertaken. 

 

Appendixes and Evidence Tables for this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/famhistimprov/famhimp.pdf.

17 
Figure 1. Analytic framework for the research questions evaluated in this review 

18

Abbreviations: FH=family history; Q=question 

An indicator of how well the clients report FH as a function of the disease type 

A measurement of the accuracy with which FH identifies or predicts a future clinical condition or disease 

Q3-Q4: Degree to which benharms are provided by FH (inindividual, social, legal, and eoutcomes) 

COLLECTING FH Q1: Optimal FH elements for predicting disease

Q2: Accuracy of Self-reporting FH Q5: Barriers and facilitators to 

collecting FH 

Q4: Impact of FH on negative outcomes Q3: Impact of FH on positive outcomes 

Q5: Includes factors from patproviders, or system 
Eligibility Criteria 

A list of eligibility criteria was determined and standardized forms were developed in 

Systematic Review Software (SRS, 3.0, TrialStat Corporation, Ottawa, Ontario Canada) and 

Microsoft Excel for the purposes of this systematic review. 

Publication Year, Type, and Language 

Inclusion 

Language: Only English language studies were eligible for all research questions. 

Publication Date: 1995 to March 2, 2009. 

Exclusion 

Publications that were editorials, letters, conference papers, comments, opinions, or abstract 

only 

Eligibility Criteria for Research Q1 

Population Subjects 

Inclusion 

• General population in non-specialist setting 

• Primary care patients in non-specialist setting 

• Participants in organized screening programs not based on FH

Exclusion 

• Patients undergoing or having completed genetic testing, whether positive or negative 

• Participants selected because of higher than average risk of disease 

• None of the disease groups of interest 

Intervention 

Inclusion 

• Family history collection – any modality 

• We delimited this research question based on the disease categories suggested by the 

OMAR Conference Planning Committee and in consultation with the Technical Expert 

Panel (TEP). These included 

• Cardiovascular diseases (including stroke and inherited childhood heart conditions) 

• Diabetes 

• Cancer (lung, breast, colorectal, ovarian, prostate) 

• Allergy and atopy (limited to asthma specifically, and atopic disease as a group) 

• Mental health disorders (major depression, mood disorders) 

Exclusion 

• Medical history without FH collection 

• Family history collection about diseases other than those specified in the inclusion 

itative, analytic design, in which the association between one or more FH items 

(considered ‘exposure’) is examined in relation to current disease or future disease risk. With the 

criteria 

Comparator/Study Design 

Inclusion 

Any quant

19 
exceptions of atopy, allergy and mental illness studies, associations were restricted to FH a

outcome of the same condition (e.g., association of FH of colorectal cancer and incidence of 

colorectal cancer but not FH of lung cancer and incidence of colorectal cancer) 

Exclusion 

• Case control studies 

nd 

e reports 

clusion 

valence or incidence of one of the disease conditions specified by the OMAR 

mittee and the TEP (cardiovascular including stroke and inherited childhood heart 

-disease or outcomes 

ajor disease categories 

• Cas

• Qualitative designs 

Outcome 

In

• Pre

com

conditions, diabetes, cancer, allergy and atopy and mental health disorders) 

• Outcomes were restricted to clinically evident or routinely ascertainable disease 

outcomes. Table 1 details the specific outcomes within each disease category

Exclusion 

• Outcomes for diseases other than those listed in Table 1 

• Pre

• Research-based outcomes not in routine clinical use 

Table 1. List of included and excluded outcomes for Question 1 by m

DISEASE 

CATEGORY 

INCLUDE EXCLUDE

Coron

dise

• Angina 

• (Acute) Myocardial infarction (AMI, 

A

• Coronary a ation 

• Intimal media thic 

se 

ary artery 

ase (CAD) 

(synonyms: ischem

heart disease, 

ic MI) 

coronary heart 

disease) 

• Revascularization (CABG, 

angioplasty) 

• Heart failure secondary to C

• CAD death 

D • Valvular heart disea

• CAD (not otherwise specified) 

rtery calcific

kness

• Hypertension 

• Aneurysm 

• Peripheral vascular disease 

Stroke 

(synonym: 

vascula

arent stroke ck 

• Subarachnoid hemorrhage not 

cified) 

cerebro r

accident) 

• Clinically app • Transient ischemic atta

otherwise specified 

• Convulsions (not otherwise 

specified) 

• Dementia (not otherwise spe

Childhood/inherited 

/congenital heart 

• Hypertrophic obstructive 

cardiomyopathy 

disease • Long QT syndrome 

Depression and 

mood disorders 

• Depression 

• Bipolar affective diso

anic/de

rder (also 

pressive 

 Other psychiatric conditions 

known as m

psychosis) 

• Schizophrenia 

• Anxiety related disorders 

•

Diabetes • Impaired fasting glucose alone 

• Impaired glucose tolerance alone 

• Metabolic syndrome 

• Type 1 diabetes 

• Type 2 diabetes 

• Gestational diabetes 

20 
Table 1. List of included and excluded outcomes for Question 1 by major disease categories (continued) 

DISEASE 

CATEGORY 

INCLUDE EXCLUDE

Allergy and Asthma • Asthma 

• Atopic dise d as an 

overall category (defined in 

s ‘atopic disease’ either 

• Food intolerance alone 

• Eczema alo

• Allergic rhinitis/sinusitis alone 

ase examine

reports a

as a general class of conditions

as a composite including at l

two of atopic asthma/wheeze, 

allergic dermatitis, specific food 

intolerance, allergic 

rhinitis/sinusitis) 

 or 

east 

ne 

Cancer • Breast cancer • Other cancers 

• Ovarian cancer 

• Colorectal cancer 

• Prostate cancer

• Lung cancer 

Abbreviations: CABG=coronar =coronary artery disea I=acute myocardial infarction; MImyocardial infarction; wave and end of the T Wave in the hearts’ electrical system 

ily physicians, general internists, obstetricians, 

s, nurse practitioners, physicians assistants, nutritionists, and 

d that had genetic testing completed, whether positive or negative 

n 

st: FH collected in any modality 

nce Standard (verification of disease status in relatives) to include any of the 

lowing: 

 records 

th relatives 

latives’ physicians

 research databases only if medical records were contained within 

y artery bypass graft; CAD

f Q

se; AM

QT interval=time between start o

Eligibility Criteria for Research Q2 

Population 

Inclusion 

• General population 

• Primary care patients 

• Primary care providers (including fam

gynecologists, nurse

behavioralists) 

• Patients from specialized disease centers 

Exclusion 

• Patients recruite

 

Interventio

Inclusion 

• Index Te

• Refere

fol

• Death registries 

• Disease registries

• Medical

• Direct contact wi

• Confirmation by re

• Verification from

 them

Exclusion 

• Index Test: Collection of medical history without FH 

21 
• Reference Standard

not include the methods listed 

as to compare differences with documentation in medical charts

Stu

clusion 

ntitative design, comparative or non-comparative 

clusion 

ics of study accuracy 

Sensitivity 

dictive value 

dictive value 

FH collection 

 measure of accuracy 

 no additional information to 

lone

ce of the highest methodological quality 

 the intervention (systematic collection or use of 

H

ral population in non-specialist setting 

ary care patients in non-specialist setting 

sicians, general internists, obstetricians, 

ician assistants, nutritionists, and 

er surgeon, oncologist, 

ents recruited on the basis of genetic testing whether results were positive or negative 

• Verification of disease status in relatives that does 

above

• Studies where patient report of FH was the reference standard and the focus of the

study w

dy Design 

In

• Any qua

Exclusion 

• Case report 

Outcomes 

In

• Metr

•

• Specificity 

• Positive pre

• Negative pre

• Measures of completeness of 

• Percent Agreement/Kappa as a

Exclusion 

• Studies where only true positives were reported, with

calculate sensitivity or specificity 

• Studies that did not report any outcomes listed above

• Studies that evaluated test-retest reliability a

Eligibility Criteria for Research Q3 

Consistent with the intent of the question, eviden

(direct evidence) was sought. Only studies where

F ) was contrasted to a comparator that did not use FH were sought. The comparator could be

between groups (for example, usual care) or within groups (before and after intervention). 

Population 

Inclusion 

• Gene

• Prim

• Primary care providers (including family phy

gynecologists, nurses, nurse practitioners, phys

behavioralists) 

• Participants in organized screening programs not based on FH

Exclusion 

• Studies where the practitioner is specialist (e.g., geneticist, canc

cardiologist) 

• Pati

22 
Intervention 

Inclusion 

• Collection or use of FH collected in a systematic manner; can be in isolation or part of a 

icative risk assessment 

 another intervention) 

ily history is used as a selection criteria for study, not as an intervention 

Primary studies of the following study designs 

d trials 

n-randomized controlled trials 

tion 

 group receiving preventive advice without provision of FH-based 

 studies 

e series and case reports 

• Disease-specific mortality 

ase-specific morbidity 

take of behavior or screening as a result of taking a FH and informing the subject of 

y Criteria for Research Q4 

Consistent with the intent of the question, evidence of the highest methodological quality 

 the intervention (systematic collection or use of 

H) was contrasted to a comparator that did not use FH were sought. The comparator could be 

betw

multipl

Exclusion 

• Collection of FH is not part of the intervention (e.g., patients selected on the basis of 

increased risk including FH for

• Fam

Comparator/Study Design 

Inclusion 

• Randomized controlle

• No

• Uncontrolled before-after studies 

Comparators: 

• No between group comparator 

• Comparator group with no interven

• Comparator

information 

Exclusion 

• Cohort studies 

• Case-control

• Cas

Outcomes 

Inclusion 

• Dise

• Up

their risk 

Exclusion 

None of the outcomes listed above 

Eligibilit

(direct evidence) was sought. Only studies where

F

een groups (for example, usual care) or within groups (before and after intervention). 

Population 

Inclusion 

23 
• General population in non-specialist setting 

mary care providers (including family physicians, general internists, obstetricians, 

ysicians assistants, nutritionists, and 

e practitioner is specialist (e.g., geneticist, cancer surgeon, oncologist, 

f genetic testing whether results were positive or negative 

icative risk assessment 

ily history is used as a selection criteria for study, NOT intervention 

d trials 

n-randomized controlled trials 

olled trials) 

r group with intervention not based on FH collection or FH-based preventive 

ntrol studies 

e series and case reports 

• Quality of life 

ily functioning 

ial functioning 

istress e.g., worry, anxiety, depression, inaccurate risk perception 

llection and /or use only, not to the resulting intervention 

• Primary care patients in non-specialist setting 

• Pri

gynecologists, nurses, nurse practitioners, ph

behavioralists) 

• Participants in organized screening programs not based on FH

Exclusion 

• Studies where th

cardiologist) 

• Patients recruited on the basis o

Intervention 

Inclusion 

• Collection or use of FH collected in a systematic manner; can be in isolation or part of a 

multipl

Exclusion 

• Collection of FH is not part of the intervention. e.g., patients selected on basis of 

increased risk including FH for another intervention 

• Fam

Comparator/Study Design 

Inclusion 

Primary studies of the following study designs 

• Randomized controlle

• No

• Uncontrolled before-after studies (non-contr

Comparators 

• No comparator group 

• Comparator group with no intervention 

• Comparato

advice 

Exclusion 

• Cohort studies 

• Case-co

• Cas

Outcome 

Inclusion 

• Fam

• Soc

• Psychological d

• Related to the FH co

Exclusion 

• Outcomes not listed above 

24 
Eligibility Criteria for Research Q5 

Population 

Inclusion 

ng 

• Primary care patients in non-specialist setting 

ily physicians, general internists, obstetricians, 

ecologists, nurses, nurse practitioners, physician assistants, nutritionists, and 

ot based on FH

st, 

e or negative 

ection 

n

 patient-specific, practitioner-specific, and setting-specific. These include: 

social 

ovider) 

antitative design, comparative or non-comparative 

design

asure of FH collection or use. Metric to assess FH 

ributes that determine if FH reported (either yes/no or extent of FH) 

ributes that determine if FH discussed (either yes/no or extent of FH) 

• General population in non-specialist setti

• Primary care providers (including fam

gyn

behavioralists) 

• Participants in organized screening programs n

Exclusion 

• Studies where the practitioner is a specialist (e.g., geneticist, cancer surgeon, oncologi

cardiologist) 

• Patients recruited with genetic testing complete, whether positiv

Inte ve r ntion 

Inclusion 

Factors (independent variables) that positively OR negatively affect either the coll

a d or use of FH, or the extent a / nd quality of FH collected or used. 

Factors can be

• Psycho

• Socio-demographic (e.g., ethnicity; gender) 

• Financial 

• Relationship of patient with healthcare provider (e.g., new provider/established pr

Exclusion 

• None 

Comparator/Study Design 

Inclusion 

• Any qu

Exclusion 

• Any qualitative study 

Out mco e 

Inclusion 

Se f reported FH by patient or me l

collection or use include: 

• Att

• Att

• Attributes that determine if FH used (either yes/no or extent of FH) 

Exclusion 

None 

25 
Study Selection 

A team of study assistants was trained to apply the eligibility criteria for screening the title 

nd abstract lists and the full text papers. All levels of screening were done in web-based 

ware (SRS) (TrialStat Corporation, Ottawa, Ontario Canada). 

Standardized forms and a training manual explaining the criteria were developed and reviewed 

wit

creening 

ed for use in SRS (Appendix B). All eligible 

udies from full text screening were abstracted onto a data form according to predetermined 

ctor transferred the data onto these forms, and another checked the 

answers for accuracy before they were entered into SRS. Data entries were verified by the 

inv

sidered the 

ssessment of quality separately for each research question. For Q1, the large number of studies 

 and disease types, which served in part, to stratify studies by 

sim ar risk for biases. The study designs for the eligible studies of Q1 were classified as 

lon

3 of the QUADAS were not applicable to collecting FH from 

info

dies. 

 before 

bias 

(me

a

Systematic Review Soft

h the screeners (Appendix B). For the title and abstract phase, two reviewers evaluated each 

citation for eligibility. Articles were retrieved if either one of the reviewers judged it as meeting 

eligibility criteria or if there was insufficient information to determine eligibility. For s

of full text articles, two screeners came to consensus on the identification, selection, and 

abstraction of information. Disagreements that could not be resolved by consensus were resolved

by one of our McMaster research team members. 

Data Extraction 

Appropriate data collection forms were develop

st

criteria. One data extra

estigators responsible for summarizing the different report results sections. 

Quality Assessment 

Given the diversity of research questions and eligible study designs, we con

a

were grouped by study design

il

gitudinal and cross sectional. Cohort studies where FH was assessed at the same point as

disease outcome was ascertained were considered cross sectional studies. For quality assessment 

we selected questions on method of sampling, and participation rates for the cross sectional 

studies; we evaluated method of disease outcome ascertainment, method of family history

ascertainment, and an accounting of withdrawals for all study designs (see Appendix B forms for 

the specification of the criteria). 

For Q2, the Quality Assessment of Diagnostic Accuracy Assessment (QUADAS) was 

selected and all but four items within the 14 criteria were applicable for the “index test” of 

collecting FH. Appendix B details the criteria and the method of standardizing responses. 

Criteria from items 3, 4, 12, and 1

rmants and verifying the diseases in relatives. In applying these QUADAS items, we 

assumed that the index test (FH collection) and the reference test were equivalent across stu

Appendix B shows the modifications and interpretation of the QUADAS for this question. 

There were two different designs among studies eligible for research Q3 and Q4; for the 

randomized clinical trials, the Jadad scale155 was used to evaluate internal validity. For the

after study design no formal scale was available, critical appraisal was undertaken for the risk of 

selection and outcome biases. For eligible cross sectional studies for research Q5, selection 

thod of sampling) and response bias were evaluated. 

26 
Summarizing our Findings: Descriptive and Analytic 

Approaches 

A q omes 

for all ether 

and treated as a single study with the m rted for presentation of summary 

sults. Standardized summary tables explaining important study population and population 

cha

cause of significant clinical heterogeneity 

acro

s. Clinical 

erall discriminatory 

acc

r each 

taken 

, TN, 

nitions to 

 notion of ‘likely effort required’, not on any a priori notion of the 

info

t 

imated the area under the curve (AUC) and the index Q* 

and

are 

ualitative descriptive approach was used to summarize study characteristics and outc

research questions. Multiple publications on the same study cohort were grouped tog

ost current data repo

re

racteristics, as well as study results, were created. 

Meta-analysis was not appropriate for any of the research questions. It was not undertaken 

for Q1 because of significant clinical heterogeneity across studies, and because many 

observations were compared within studies, therefore the studies were not completely 

independent. Similarly, it was not undertaken in Q2 be

ss studies, too few studies for some disease categories, or insufficient data (no measures of 

variance). There were an insufficient number of studies in Q3 and Q4 for meta-analysi

and methodological heterogeneity was significant for eligible studies in Q5. 

For research Q1, the purpose of the analysis was to compare the discriminatory accuracy of 

specific FH items and definitions of ‘positive’ FH which might be used in routine clinical 

practice. The ideal method would have been a meta-regression analysis to assess the contribution 

of the different variables of interest (ancestry, lineage, age of onset, etc) to ov

uracy. However, no studies were identified which permitted such an analysis. In order to 

address the research question, therefore, a simpler, alternative approach was developed. Fo

study, all definitions of ‘positive FH’ which were associated with analyzable data (see below) 

were recorded and, within disease condition, similar FH definitions (e.g., ‘mother’, ‘father’, ‘at 

least one 1DR’, etc.,) were grouped for comparison. We approached the definitions from a 

pragmatic clinical perspective, rather than epidemiological perspective so that in studies with 

multiple definitions we combined data from mutually exclusive categories into inclusive 

categories. For example, the category ‘affected mother’ included data from the categories 

‘mother only’ and ‘both parents’. Thus, the category “affected mother” should generally be 

to mean, “affected mother, whether or not the father also affected. 

We extracted the actual numbers of true and false positive and negative results (TP, FP

and FN) according to these definitions, or estimated these numbers based on reported 

proportions. We calculated sensitivities, and specificities with the accompanying 95 percent 

confidence intervals (CI). 

Recognizing the primary care context for the review, in which the time and resources 

available for FH taking may be very limited, we developed a categorization of FH defi

reflect the ‘complexity’ of the task (Table 2). It is important to note that this initial attempt at

categorization is based on a

rmation value of the pedigree itself. We suggest that the FH definition that combines 

‘adequate’ predictive validity with least effort (lowest category) might be the most likely to be 

useful in routine primary care settings. 

Summary receiver operator characteristic (SROC) curves were estimated to assess the effec

on accuracy of different FH definitions within each major disease group. The SROC curve

mimics the receiver operator characteristic (ROC) curve and is a way to measure the diagnostic 

accuracy across different studies. We est

 their standard errors. The value of Q* indicates overall accuracy by finding where sensitivity

and specificity are equal. Since Q* is defined by the point where sensitivity and specificity 

27 
equal, Q* may not address the clinical usefulness of the test when sensitivity and specificity are 

not equally important in practice. Note that a minimum of three studies with the same FH 

definition would be required for this computation. Statistical analyses were carried out using 

Stata/SE 8.0 for Windows (Stata Corporation) or MetaDiSc.156 Additionally, data points entered

into the analyses had to be independent; as such, we selected the most inclusive FH definition 

within each family history category (Table 2). For example, data from a single study report

values for greater than or equal to one parent, mother, and father would not be independent; th

data from greater than one parent was selected to include in the SROC analyses. 

Table 2. Notional classification of family history items and definition of a positive family history 

Category 

General 

approach to 

FH collection 

“Positive” FH Example Workload 

ing 

e 

A 

que

e 

d 

One single 

affected by 

condition, 

relationship 

Does anyo ily 

have the condition?

•

ive 

• Workload very low if 

approac le 

ing 

rtain 

Ask the most 

general 

 Enquiry stops if patient recalls 

one affected relat

stion to 

dentify one 

affected family 

i

member whos

relationship

does not nee

to be specified 

relative 

irrelevant 

ne in your fam s

hed as simp

creening question 

• Workload higher if approached 

by systematically work

through pedigree to asce

relatives’ status 

B 

2 

no others. 

relatives 

affected by 

condition 

have the condition? 

Does your brother have th

condition? 

Did your mother have thi

Ask about 1-

specific family 

members, and 

One or two 

defined 

Do either of your parents 

e 

s 

• Enquiry stops when 

affected/unaffected status of no 

more than 2 specified relatives

is clarified 

condition? If so, do you 

also have a sister with it? 

• Workload potentially very low 

C 

Ask about 

close family 

only 

ot 

pre-specified 

further) brothers or sisters been 

t 

One or more 

first degree 

relatives (n

affected by 

condition 

Does any member of your 

immediate family have the 

condition? 

Have any of your parents, 

affected by this condition? 

• Enquiry stops when the 

minimum number of specified 

affected relatives is reached 

OR unaffected status of all firs

degree relatives clarified 

• Workload depends on number 

of siblings and children, but 

enquiry limited by number of 

first degree relatives 

D 

Be ready to go 

beyond close 

family but do 

not consider 

/or 

ird 

degree 

Have any of your 

immediate or broader 

family (aunts, uncle

grandparents, etc.) have 

lineage 

One or more 

first and/or 

second, and

[possibly] th

relatives (but 

not prespecified 

further) 

affected by 

condition 

s, of interest is clarified 

• Workload depends on number 

of relatives in close and 

extended family and how far FH 

criteria extend beyond first 

degree 

the condition?

• Enquiry stops when minimum 

number of specified affected 

relatives is reached OR 

unaffected status of all relatives 

Abbreviations: FH=family history 

28 
29 

 of family history items and definition of a positive family history (continued) 

Category 

General 

approach to 

FH collection

“Positive” FH Example Workload

Table 2. Notional classification

E 

Follow specific 

guidelines 

which define 

relevant FH 

history in a 

more complex 

manner or 

which go 

beyond 

affected 

relatives 

More complex 

combination of 

numbers, 

degree of 

relationship, 

and/or lineage 

of relatives 

affected by 

condition, 

and/or 

considerations 

such as 

consanguinity 

Have at least two 

immediate relatives from 

the same side of the family 

(i.e., excluding both parents 

but including one parent 

and a brother or sister or 

two of your brothers and 

sisters) been diagnosed 

with the condition? 

If not, has one immediate 

relative and at least two of 

your aunts, uncles, 

grandmother, grandfather, 

nieces or nephews (on the 

same side of the family) 

been diagnosed with the 

condition? If not, have at 

least three of your aunts, 

uncles, grandmother, 

grandfather, nieces, and/or 

nephews (on the same side 

of the family) been 

diagnosed with the 

condition? 

• Enquiry stops when the criteria 

for positive FH are met OR the 

unaffected status of relatives of 

interest is clarified. 

• Workload variable, depends on 

complexity of criteria and 

number of relatives potentially 

of interest 

Peer Review Process 

The partner organization, TOO, research team, and members of the TEP identified potential 

peer reviewers. The MU-EPC compiled a list of these reviewers, all of whom were approved by 

the AHRQ prior to the circulation of the draft report. 

A draft version of this report was circulated to 10 peer reviewers (see Appendix E). The 

reviewers represented clinicians and expert in family medicine/primary care, cancer, 

cardiovascular disease, diabetes, asthma, genetics, and family history. The reviewers were 

provided with a standardized form to solicit feedback on the methods of the review, the 

presentation of the information and the interpretation of the results. Where possible, comments 

and suggestions were incorporated. 

 

 

Chapter 3. Results 

Figure 2 details the flow of studies and the final subset for reviewing. The search yielded 

32,444 unique citations. During three levels of title and abstract screening, 31,190 articles were 

excluded. A total of 1,254 citations proceeded to full text screening. After the final eligibility 

screening, 137 publications were eligible for data extraction. 

Figure 2. Flow of studies through review 

 

1st Excluded at 1st Title and Abstract Screening 

n=32,444 

 title and abstract 

n=29,192 

Appendixes and Evidence Tables for this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/famhistimprov/famhimp.pdf.

Eligible Studies n=1,071

2nd

 Title and Abstract Screening 

n=3,252 

Excluded at 3rd title and abstract 

n=505 

Full Text 

Screening 

n=1,254 

183 Excluded from Full Text 

Not an eligible population...................................14

Family history is not collected ............................31

Not an eligible study design ...............................16

No eligible outcomes presented.......................122

Question 1 

n=89 

Question 2 

n=37 

Question 3

n=2 

Question 4

n=3 

Question 5 

n=6 

Excluded at 2nd title and abstract 

n=1,493 

3 rd Title and Abstract Screening 

n=1,759 

Not applicable to any 

specific review question 

n=934 

31 
Question 1. What are the Key Elements of a Family History in 

a Primary Care Setting for the Purposes of Risk Assessment 

re identified that met the eligibility criteria, reported family 

63

s 

the summary receiver operator characteristics (SROC) curve and area under the curve (AUC), 

provides an overall assessment of accuracy of classification. Note that the SROC curve could 

e FH definition. An AUC of 1.0 

for Common Diseases? 

Introduction 

Sixty-one reports of 59 studies we

history (FH) definitions, and presented data which could be analyzed.2-62 In addition, one paper

did not present data which could be included in the m ly 

summarized because the data were directly relevant to the resear n. A further 17 

papers64-80 were eligible but did not define FH, and 10 papers81-90 did not report interpretable 

data. These are excluded from the results below. 

Note on Interpretation of Results 

Data are presented below for both longitudinal and cross sectional analyses. The most 

common approach to

association (i.e., how many times higher the incidence or prevalence of the disorder is in people 

with the FH than people without). The metrics used can include relative risk (RR), odds ratio 

(OR), hazard ratio (HR) and others. These do not provide an estimate of individual probability of 

disease. For this systematic review, FH is approached as if it was a ‘test’, and predictive 

accuracy metrics are used to judge performance. definition is 

considered to be t ‘calibration poin fo

the ‘FH test’. The longitudinal analyses prov tio

predict the occurr uture disease in in

analyses provide an estimate of how well dif

individuals who currently have and do not have the disease of interest. Longitudinal studies 

examine prediction of future cases, while cross sectional studies examine current disease. Four 

metrics are ance of different FH definitions: 

• Sensitivity – provides an estimate of the proportion of future or current cases which are 

correctly identified by the particular ‘positive’ FH de

• Specificity – provides an estimate of the proportion of individuals destined to be disease-free

who are correctly identified by not meeting the particular FH definition 

• Positive predictive value (PPV) – indicates the proportion of individuals who meet the 

particular FH definition who will actually develop or currently have the disease 

• Negative predictive value (NPV) – indicates the proportion of individuals who do not meet 

the particular FH definition who will remain disease free or do not currently have the 

disease. 

PPV and NPV are influenced by the underlying prevalence of the disease i tion

studied – the higher the prevalence, the higher the PPV and the lower the NPV, and vice versa. 

Sensitivity and specificity are not influenced by disease prevalence. The final metric, area under 

ain analysis, but was descriptive

ch questio

 assessing the contribution of FH to disease risk is to measure strength of 

 In this situation, each FH

a differen t’ (the cutoff for ‘positive’ or ‘negative’ result) r 

ide an estimate of how well different FH defini n

ence of f dividual study participants. The cross sectional

ferent FH definitions discriminate between 

 used to assess the perform

finition 

n the popula

only be computed if a minimum of three studies had the sam

32 
indicates a perfectly calibrated test – 100 percent of individuals are correctly classified as 

affected or unaffected. An AUC of 0.5 indicates that the test as calibrated correctly classifies 

ifty percent of individuals into affected and unaffected and therefore is no better than chance. 

ests the test is worse than chance. The 

f

An AUC of less than 0.5 sugg ‘ideal’ calibration of a test 

.e., the ‘best’ FH definition) depends on whether the goal is to prioritize sensitivity (lowest 

 missing real cases), specificity (lowest possible chance of false positives), or 

sification (the highest AUC). 

gn,3,4

 in 

rom 1,445 to 115,460. The longest followup 

eriods for the longitudinal studies were 12 months4

 and 8 years.3 Please see Webtables 2 and 3 

t cancer, and the diagnostic criteria used to define 

e latter. 

ined 

l 

.e., 

ion 

 were not 

86- 

t in the study samples. 

cy in 

d 

k 

ast cancer incidence (in longitudinal studies) and was positively associated 

it

n 

8 

(i

possible chance of

overall accuracy of clas

Breast Cancer 

Four studies were included (see Webtable 1, Appendix C), two with a longitudinal desi

and two cross sectional.5,6 Two studies were conducted in the U.S.,3,6 one in Canada,4

 and one

the United Arab Emirates.5 Sample sizes ranged f

p

for the methods used to ascertain FH and breas

th

Family history. Four definitions of ‘positive FH’ based on affected relatives were exam

in five analyses, all focusing on first degree relatives (1DRs) in some combination. They all fel

into Category C or E (see Table 2, Chapter 2); in addition, one study examined parental 

consanguinity. Three of the studies reported the strength of association between positive FH (i

affected relatives) and breast cancer risk in terms of relative risk or odds ratio. Depending on the 

FH definition used, these ranged from 1.37 to 2.83. A relative risk of 0.66 for the associat

between parent consanguinity and breast cancer was reported5

 but the data in this report

examined for a FH of affected relatives. These data are presented for each FH definition in 

Webtable 4, Appendix C.

Predictive accuracy. Figures 3 to 6 present sensitivity and specificity data for these FH 

definitions. 

For the longitudinal analyses, the range of sensitivities was 0.06-0.26, and specificities 0.

0.95. The range of positive predictive values (PPVs) was 0.01-0.05, and negative predictive 

values (NPVs) 0.98-0.99, for breast cancer prevalences up to 2.5 percen

For the cross-sectional analyses, the sensitivities were 0.05 and 0.15, with corresponding 

specificities of 0.97 and 0.90. The PPVs were 0.01 and 0.09 and NPVs were 0.99 and 0.95, for 

prevalences of 0.7 and 5.4 percent, respectively. It was not possible to calculate AUC. 

Conclusion. These analyses were limited by the very few discrete FH definitions available 

for comparison, and the heterogeneity of the studies in terms of underlying disease frequen

the study samples, length of followup, method of disease ascertainment, and other factors. 

With the exception of the parental consanguinity analysis, the definitions of positive FH use

in these studies were consistently associated with elevated relative risks (Webtable 4), (i.e., a 

positive FH of cancer in relatives), at a population level. However defined, it was also a ris

factor for future bre

w h the presence of current breast cancer (in cross-sectional studies). Within the analyses 

examined, the most sensitive FH marker for future breast cancer appeared to be ‘at least one 

affected 1DR’: this is a ‘low complexity’ approach to FH (see Table 2). In the single longitudinal

study which used it, this definition correctly identified 26 percent of women who went on to 

develop breast cancer within 4-8 years (with a false positive rates of 12 percent).3

 The proportio

of participants with a positive FH defined thus who actually developed breast cancer within 4-

33 
years was 5 percent. PPV is dependent on underlying disease frequency, which was 2.5 pe

Thus, it can be tentatively concluded that a simple definition of positive FH, based on one 1DR

(assumed female) with breast cancer, appeared to be associated with the highest sensitivity for 

future breast cancer risk within 4-8 years, but that, as always, the predictive ability in practice 

depends on the breast cancer prevalence in the patient population to whom it was being applie

These observations need to be replicated in further studies which also clarify the contribution of 

FH information to overall risk prediction based on oth

rcent. 

d. 

er established risk factors. Conclusions 

garding FH definitions used in a cross-sectional (prevalence screening) approach are not 

fficient analyses were available with a range of definitions. However, there 

ould not appear to be a rationale for breast cancer screening triage on the basis of FH in the 

con

nal study scored less well across almost all items because of incomplete reporting, 

mak

re

possible because insu

w

text of widespread access to effective alternative screening technologies. 

Quality assessment. The two longitudinal studies and one of the cross-sectional studies6

scored highly on all or most quality assessment items despite that fact that two of the published 

reports4,6 did not indicate clearly that the same method of FH ascertainment had been applied to 

all participants. Overall, these studies were judged to be at low risk of significant bias. One 

cross-sectio 5

ing it difficult to judge the likelihood of important bias. See Webtable 5, Appendix C. 

34 
Figure 3. Breast Cancer, Longitudinal Studies, Sensitivity 

Abbreviations: 1DR=first degree relative; CI=confidence interval 

Figure 4. Breast Cancer, Longitudinal Studies, Specificity 

Abbreviations: 1DR=first degree relative; CI=confidence interval 

Study

 Sensitivity

(95% CI)

>=1 1DR female (C)

Cauley 2007 0.26 ( 0.16, 0.38)

 >=1 1DR breast >=50y/1 1DR ovarian (E)

Halapy 2005 0.19 ( 0.16, 0.22)

 >=2 1DR breast/ovarian any age/>=1 1DR breast <50y/>=1 1DR breast and ovarian (E) 

 Halapy 2005 0.06 ( 0.04, 0.08)

-.25

Specificity

 -.5 -.25 0 .25 .5 .75 1

Study

 Specificity

(95% CI)

 >=1 1DR female (C)

Cauley 2007 0.88 ( 0.87, 0.89)

 >=1 1DR breast >=50y/1 1DR ovarian (E)

Halapy 2005 0.86 ( 0.85, 0.86)

>=2 1DR breast/ovarian any age/>=1 1DR breast <50y/>=1 1DR breast and ovarian (E) 

Halapy 2005 0.95 ( 0.95, 0.95)

 Sensitivity

 -.5 0 .25 .5 .75 1

35 
Figure 5. Breast Cancer, Cross-sectional Studies, Sensitivity 

 Sensitivity

 -.5 -.25

 Sensitivity

 Study (95% CI)

>=1 1DR (C)

 Denic 2001 0.05 ( 0.01, 0.13)

 Kerlikowske 1997 0.15 ( 0.11, 0.20)

 Consanguineous parents (E)

 Denic 2001 0.31 ( 0.21, 0.42)

 0 .25 .5 .75 1

bbreviations: 1DR=first degree relative; CI=confidence interval 

ty 

A

Figure 6. Breast Cancer, Cross-sectional Studies, Specifici

 Specificity

 Study (95% CI)

 >=1 1DR (C)

 Denic 2001 0.97 ( 0.96, 0.98)

 Kerlikowske 1997 0.90 ( 0.90, 0.90)

 Consanguineous parents (E)

 Denic 2001 0.59 ( 0.57, 0.62)

 -.5

Abbreviations: 1DR=first degree relative; CI=confidence interval 

 Specificity

 -.25 0 .25 .5 .75 1

36 
Colorectal Cancer 

Three studies were included in the colorectal cancer (CRC) a Webtable 1, 

Appendix C), one longitudinal (with data derived from two sepa l cohort stud

with male, and the other with female participants),7

 and two cross-sectional.8,9 One was 

conducted in a U.S. population7

 one in the U.K,8 and one in several Asian cities.9

ranged from 860 to 134,365. The followup periods reported in the longitudinal study were 14 

ye ale cohort and 20 years for the male cohort.7 Please see Webtables 6

Appendix C for the methods used to ascertain FH and CRC, and the diagnostic criteria em

fo

Family history. Four definitions of ‘positive FH’ were examined, all focusing on 1DRs and 

all in Category C (Table 2). One study8 examined multiple definitions within the same

and reported analyses by gender, and by age of onset of cancer. All three publications reported 

the strength of association between positive FH and colorectal cancer risk in terms of

Depending on the FH definition used, and the outcome (all disea ase)

ranged from 1.33 to 5.29. The data by specific FH definition are presented in Webtable 4, 

Appendix C. 

Predictive accuracy. Figures 7 through 10 present sensitivity and specificity data for these 

FH definitions. 

The interp io naly s l d because only one criterion for 

positive FH is used, (>=1 1DR). Sensitivities of 0.13 and 0.14 were obtained for the ma

nalysis (see 

rate origina ies, one 

 Samples sizes 

 and 7, in 

ployed 

 dataset 

 RR or OR. 

 of these 

le and 

 of around 1 percent. 

cities 

les and one 

 was 

ising in 

of 0.02 

ed (would 

icities 

 this, the 

ce 

ars for the fem

r the latter. 

se or premature dise

retat n of the longitudinal a ses i imite

female cohorts with a specificity of 0.92 for both. For both cohorts, the PPVs were 0.02 and the 

NPVs 0.99, for underlying colorectal cancer prevalence

For the cross-sectional analyses, the range of sensitivities was 0.00 to 0.20, and specifi

0.88 to 1.00. The range of PPVs was 0.00 to 0.07 and NPVs of 0.96 or higher, for overall CRC 

prevalences ranging from <1 to 4.5 percent. It was not possible to calculate AUC for either the 

longitud nal or cross-sectional data. The AUC for category C FH d as 0.64. 

Conclusion. These analyses were limited by the relatively few discrete FH definitions 

available for comparison. The two longitudinal analyses reported in a single report appeared to 

be fairly homogeneous in terms of participant characteristics, albe

ex imple definition of ‘ DR)

as lity to correctly identify around 13-14 percent of cases of CRC ar

the subsequent 16-20 years, with a false positive rate of about 8 pe PV 

would imply that 98 percent of the ‘FH positive’ individuals would be wrongly classifi

not develop CRC). It is likely that some of the latter avoided cancer through screening and the 

r s (thus the FH ‘test’ was not strictly ‘wrong’). However, the 

larger the proportion of the population meeting the FH criterion (around 8 percent in this study), 

the higher the chance of unnecessary clinical intervention. 

In relation to the two cross-sectional studies, a wide range of sensitivities and specif

were observed, due in part to the multiple analyses performed within one dataset,8

 making it 

difficult to discern any pattern across definitions of different complexity. Irrespective of

highest PPV was 0.07, suggesting rather low ability of any FH definition to indicate the presen

of prevalent CRC. 

emoval of pre-malignant lesion

rcent. However, a P

amined females. The results suggest that a s

sociated with an abi

it one examined ma

positive FH’ (>=1 1

i efinition w

37 
While these analyses do not, in themselves, suggest the utility of any particular positive FH 

diction of or screening for CRC, they are also not sufficient to rule out 

 to usefully augment existing predictive or screening strategies. 

ree it 

l 

definition in relation to pre

the possibility of using FH

Quality assessment. All three studies scored highly in relation to uniform methods of 

ascertaining FH (exposure) and colorectal cancer (outcome). For two studies,7,8 it was possible 

that knowledge of disease status may have influenced ascertainment of FH, and for all th

was possible that knowledge of FH may have influenced ascertainment of colorectal cancer. The 

possibility of selection bias through attrition or low response rates could not be ruled out for al

three studies. See Webtable 5, Appendix C. 

38 
Figu

Abbreviations: 1DR=first degree relative; CI=confidence interval; CRC=colorectal cancer; F=female; M=male 

Figure 8. CRC, Longitudinal Studies, Specificity 

Abbreviations: 1DR=first degree relative; CI=confidence interval; CRC=colorectal cancer; F=female; M=male 

re 7. CRC, Longitudinal Studies, Sensitivity 

 Sensitivity

 Study (95% CI)

 >=1 1DR (C)

 Wei 2004, M 0.13 ( 0.11, 0.16)

 Wei 2004, F 0.14 ( 0.12, 0.17)

 -.5 -.25 0 .25 .5 .75 1

 Sensitivity

 Specificity

 Study (95% CI)

 >=1 1DR (C)

 Wei 2004, M 0.92 ( 0.91, 0.92)

 Wei 2004, F 0.92 ( 0.92, 0.92)

 -.5 -.25 0 .25 .5 .75 1

 Specificity

39 
Figure 9. CRC, Cross-sectional Studies, Sensitivity 

 Sensitivity

 -.5 -.25

 Study Sensitivity

 (95% CI) >=1 1DR (C)

 Sand 0.15 ( 0.0

Abbreviations: 1DR=first degree relative; CI=confidence interval; CRC=colorectal cancer; F=female; M=male 

Figure 10. CRC, Cross-sectional Studies, Specificity 

Abbreviations: 1DR=first degree relative; CI=confidence interval; CRC=colorectal cancer; F=female; M=male

 0 .25 .5 .75 1

hu 2001, M&F 9, 0.21)

 Byeon 2007, M&F 0.20 ( 0.09, 0.37)

 Sandhu 2001, M 0.11 ( 0.05, 0.20)

 Sandhu 2001, F 0.19 ( 0.10, 0.30)

 Sandhu 2001, M&F, onset<60 0.10 (0.02, 0.26)

 Sandhu 2001, M&F onset <50 0.00 ( 0.00, 0.84)

 Sandhu 2001, M, onset<60 0.05 ( 0.00, 0.26)

 Sandhu 2001, M, onset<50 0.00 (0.00, 0.98)

 Sandhu 2001, F, onset<60 0.18 ( 0.02, 0.52)

 Sandhu 2001, F, onset<50 0.00 (0.00, 0.98)

 >=2 1DR (C)

 Sandhu 2001, M&F 0.02 ( 0.00, 0.06)

 >=1 1DR, onset <65 (C)

 Sandhu 2001, M&F 0.07 ( 0.04, 0.13)

 >=1 1DR,onset<45 (C)

 Sandhu 2001, M&F 0.01 ( 0.00, 0.05)

 Specificity Study (95% CI) >=1 1DR (C)

Sandhu 2001, M&F 0.93 ( 0.93, 0.94)

 Byeon 2007, M&F 0.88 ( 0.85, 0.90)

 Sandhu 2001, M 0.94 ( 0.94, 0.94)

Sandhu 2001, F 0.93 ( 0.92, 0.93)

Sandhu 2001, M&F, onset<60 0.94 ( 0.94, 0.94)

Specificity

 -.5 -.25 0 .25 .5 .75 1

Sandhu 2001, M&F, onset <50 0.95 ( 0.94, 0.95)

Sandhu 2001, M, onset<60 0.94 ( 0.94, 0.95)

 Sandhu 2001, M, onset <50 0.96 ( 0.95, 0.96)

 Sandhu 2001, F, onset <60 0.94 ( 0.93, 0.94)

Sandhu 2001, F, onset<50 0.94 ( 0.94, 0.95)

 >=2 1DR (C)

Sandhu 2001, M&F 1.00 ( 1.00, 1.00)

>=1 1DR, onset <65 (C)

Sandhu 2001, M&F 0.98 ( 0.98, 0.98)

>=1 1DR, onset<45 (C)

Sandhu 2001, M&F 1.00 ( 1.00, 1.00)

40 
 Prostate Cancer 

 and two in 

tain 

one 

ion 

 the definitions of FH used were associated with 

e 

ossity was 26 

 added 

ent 

The prostate cancer analysis was based on six studies (see We

longitudinal10-13 and two cross-sectional.14,15 One study15 reported an analysis of participants in a 

prospective cohort study, but FH was ascertained at a late stage in the study therefore it was 

treated as a cross-sectional analysis. Four were conducted in U.S. 15

Finnish populations.11,14 The average followup periods for the longitudinal studies ranged from

6.8 Appendix C for t to ascer

FH e diagnostic criteria used. 

rete definitions of ‘positive FH’ were at least 

falling in each of the categories A-E (Table 2). All studies reporte associat

betw ostate cancer risk in terms of RR or OR. Depending on the FH 

de these ranged from 0.97 to 6.5. The data by specific definition are presented in 

Webtable 4, Appendix C. 

Figures 11 through 14 present the sensitivity and specificity data for 

the ns used in these analyses. For the longitud range of

sensitivities was 0.00-0.21, and specificities 0.88-1.00. Excluding one study using mortality as 

the of PPVs was 0.11-0.26, and NPVs 0.92-0.95, for prostate cancer 

prevalences up to 8.7 percent. The AUC for category B FH definition

C FH definitions was 0.93. 

For the cro ecti anal s, ra f se iviti s 0.01-0.26 and specificities 0.91-

1.00. The PPVs were 0.02-0.14 and NPVs 0.96-0.98, for prostate cancer prevalences up to 8.7 

btable 1, Appendix C), four 

populations,10,12,13,

 to 18 years. Please see Webtables 8 and 9, in he methods used

 and prostate cancer, and th

Family history. Ten disc examined, with

d the strength of 

een positive FH and pr

finition used,

Predictive accuracy. 

various FH definitio inal analyses, the

 outcome, the range 

s was 0.51 and for category 

ss-s onal yse nge o nsit es wa

percent. The AUC could not be calculated. 

Conclusion. A range of definitions of positive FH were examined in these studies, in both 

predictive and screening contexts. Almost all of

positiv isk of future disease incidence or current disease presence. However, the definitions 

ex appeared, overall, no better than chance in predicting future presence or absenc

of prostate cancer in the participants studied. 

 an approach to identify individuals who may cted (cr

sec he sensitivities and PPVs were uniformly low. 

percent for presence of cancer and the highest PPV 14 percent in a

par of their cancer diagnosis. Further the 

info information (and specific definitions) ted if it

value when used in conjunction with other screening strategies. 

 general, the longitudinal studies scored high on quality assessm

ite exception of one13 in which key methodological details were not reported. For the 

two dies, the possibility that knowledge of FH influenced ascertainment of 

pr be ruled out, and both were possibly subject to selection bias 

through low response rates. See Webtable 5, Appendix C. 

Quality assessment. In

ms, with the 

 cross-sectional stu

ostate cancer outcomes could not 

ticipants were already aware

rmation gained from FH

 currently be affe

The highest sensitiv

 study where many 

studies to clarify

 might be warran

Regarding FH as

tional studies), t

e r

amined here 

41 
Figure 11. Prostate Cancer, Longitudinal Studies, Sensitivity 

Figu

Abbreviations: 1DR=first degree relative; CI=confidence interval 

Abbreviations: 1DR=first degree relative; CI=confidence interval 

 Sensitivity

 Study

 Sensitivity

 (95% CI)

 Father (B)

 Cerhan 1999 0.06 ( 0.02, 0.13)

>=1 brother (B)

 Cerhan 1999 0.07 ( 0.03, 0.14)

Father and/or brother (B)

 Chen 2008 0.21 ( 0.19, 0.22)

>=1 1DR (C)

 Rodriguez 1997 0.05 ( 0.04, 0.06)

 Ahn 2008 0.06 ( 0.04, 0.07)

Cerhan 1999 0.13 ( 0.07, 0.22)

 >=2 1DR (C)

 Rodriguez 1997 0.00 ( 0.00, 0.01)

 -.5 -.25 0 .25 .5 .75 1

re 12. Prostate Cancer, Longitudinal Studies, Specificity 

 Study

 Specificity

 (95% CI)

 Father (B)

 Cerhan 1999 0.97 ( 0.96, 0.98)

 >=1 brother (B)

 Cerhan 1999 0.99 ( 0.98, 0.99)

 Father and/or brother (B)

 Chen 2008 0.88 ( 0.88, 0.89)

 >=1 1DR (C)

 Rodriguez 1997 0.97 ( 0.97, 0.97)

 Ahn 2008 0.97 ( 0.97, 0.97)

 Cerhan 1999 0.96 ( 0.95, 0.97)

 >=2 1DR (C)

 Specificity

 -.5 -.25 0 .25 .5 .75 1 1.25

 Rodriguez 1997 1.00 ( 1.00, 1.00)

42 
 Figure 13. Prostate Cancer, Cross-sectional Studies, Sensitivity 

ty 

tive; CI=confidence interval 

Abbreviations: 1DR=first degree relative; CI=confidence interval 

Figure 14. Prostate Cancer, Cross-sectional Studies, Specifici

Abbreviations: 1DR=first degree relative; 2DR=second degree rela

 Sensitivity Study (95% CI) any relative (A)

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Kalish 2000 0.26 ( 0.16, 0.40)

 Father (B)

 Makinen 2002 0.04 ( 0.03, 0.06)

 >=1 brother (B)

 Makinen 2002 0.02 ( 0.01, 0.04)

 >=1 1DR (C)

 Makinen 2002 0.06 ( 0.04, 0.08)

 >=1 1DR, onset<60 (C)

 Makinen 2002 0.01 ( 0.00, 0.02)

 >=1 1DR or 2DR (D)

 Makinen 2002 0.10 ( 0.07, 0.13)

 paternal grandfather or >=1 paternal uncle (E)

 Makinen 2002 0.02 ( 0.01, 0.03)

 maternal grandf

 Makinen 2002

ather or >=1 maternal uncle (E)

 0.02 ( 0.01, 0.04)

 Specificity Study (95% CI) any relative (A)

 Kalish 2

 Specificity

 -.5 -.25 0 .25 .5 .75 1 1.25

000 0.91 ( 0.89, 0.93)

 Father (B)

 Makinen 2002 0.96 ( 0.96, 0.97)

 >=1 brother (B)

 Makinen 2002 0.99 ( 0.99, 0.99)

 >=1 1DR (C)

 Makinen 2002 0.95 ( 0.95, 0.96)

 >=1 1DR, onset<60 (C)

 Makinen 2002 1.00 ( 1.00, 1.00)

 >=1 1DR or 2DR (D)

 Makinen 2 02 0 0.92 ( 0.92, 0.93)

 paternal grandfather or >=1 paternal uncle (E)

 Makinen 2002 0.98 ( 0.98, 0.99)

 maternal grandf

 Makinen 2002

ather or >=1 maternal uncle (E)

 0.98 ( 0.98, 0.98)

43 
Coronary Heart Disease 

were included in the coronary heart disease (CHD) analysis (see We

Appendix C), five longitudinal16-20 and three cross-sectional.21-23 Four were conducted in U.S. 

po 22,23 (one in American Filipina women23) and one each in Pakistan,21 Sweden,

Fin nmark.19 One of the longitudinal studies16 reported analyses based on two 

individual cohort studies, one in men and one in women. The average followup periods for the 

longitudinal studies ranged from 6.2 to 19.6 years. Please see Webtables 11 and 12 in Appendix 

C f ds used to ascertain FH and coronary heart disease, and the various definitions 

and diagnostic criteria used. 

enteen discrete definitions of ‘positive FH’ were analyzed, with at

one in each of the categories B-E. All studies except one20 reported the strength of association 

bet nd coronary heart disease risk in terms of RR or OR. Depending on the FH 

defi ese ranged from 0.93 to 6.2. The data by specifi resented in 

We

uracy. Figures 15 through 18 present the sensit ity data

these definitions of FH. For the longitudinal analyses, the range of sensitivities was 0.03-0.51 

and specificities 0.66-0.98. The range of PPVs was 0-0.13 and NPVs 0.66-0.98, for CHD 

prevalences up to 10.4 percent. The definitions were all category B and the AUC for this 

category was 0.58. 

For the cross-sectional analyses, the range of sensitivities was 0.07-0.70 and specificities 

NPVs 0.83-0.98, for CHD prevalences up to 

Eight studies btable 10, 

17

 least 

 for 

 cross-sectional studies. 

ciation between broadness and 

le 

ts. 

ilar 

e 

ined in the 

 the 

portant 

lity 

ss of 

pendix 

pulations,

l

16,20,

and,18 and De

or the metho

Family history. Sev

ween positive FH a

nition used, th c definition are p

btable 4, Appendix C. 

Predictive acc ivity and specific

0.53-0.98. The range of PPVs was 0.08-0.31, and 

20.7 percent. The AUC could not be estimated for

Conclusion. The longitudinal analyses suggest an asso

narrowness of a minimum FH definition and sensitivity and specificity although these simp

def s as a whole classified the future CHD risk correctly for only 58 percent of participan

Th most all below 10 percent. This means that, if pr pulations are sim

to those analyzed here, at least 90 percent of individuals meeting any of the FH definitions would 

be incorrectly classified as high risk for developing CHD. The highest disease prevalence in th

cohorts studied was around 10 percent, but in some analyses, more than a third of the participants 

me tion. Generally, similar PPVs were obtained for the definitions exam

cross-sectional studies, although the analyses were dominated by a

alue of the most highly predictive FH definitions ed in

light of the predictive ability of other established factors such as blood pressure, lipid profiles, or 

ant s, and in the context of the risks and costs of available interventions to 

reduce risk, to determine whether it is likely to add significant inform

clinical settings. The underlying prevalence of disease in the patie n im

factor which needs to be taken into account. 

nal studies generally sc on qua

assessment items, with the exception of one17 where inadequate reporting made it impossible to 

ass ss-sectional studies, th warene

FH status influencing reporting of presence or absence of coronary heart disease, and vice versa, 

could not be ruled out. Also, sample selection bias could not be excluded because of nonprobability sa ng 23 r su pti esp se See Webtable 13, Ap

C. 

inition

e PPVs were al actice po

t the FH defini

 single study.22 

Overall, the v needs to be assess

hropometric measure

ation value in routine 

nt population is a

Quality a sment. sses The five longitudi ored fairly high 

ess four of the six items. For all three cro e possibility of a

mpli methods a 21, nd/o b-o mal r on rates. 

44 
Figure 15. CHD, Longitudinal Studies, Sensitivity 

iations: CHD=coronary heart disease; CI=confidence interval; F=female; M=male 

Abbreviations: CHD=coronary heart disease; CI=confidence interval; F=female; M=male 

Figure 16. CHD, Longitudinal Studies, Specificity 

Abbrev

 Sensitivity

 -.5 -.25 0 .25 .5 .75

 Study Sensitivity

 (95% CI) >=1 parent (B)

 Djousse 2008, M 0.34 ( 0.31, 0.37) Sesso 2001, M 0.46 ( 0.43, 0.50) Hippe 1999, M 0.23 ( 0.20, 0.26) Sesso 2001, F 0.41 ( 0.33, 0.49) Hippe 1999, F 0.30 ( 0.25, 0.35)

 Father (B)

 Sesso 2001, M 0.36 ( 0.33, 0.40) Piros 2000, M 0.05 ( 0.01, 0.16) Sesso 2001, F 0.27 ( 0.20, 0.35)

 Mother (B) Sesso 2001, M 0.16 ( 0.13, 0.19) Piros 2000, M 0.07 ( 0.01, 0.19) Sesso 2001, F 0.25 ( 0.19, 0.33)

 Both parents (B)

 Sesso 2001, M 0.06 ( 0.04, 0.08) Sesso 2001, F 0.11 ( 0.07, 0.17)

 >=1 parent, onset<65y (B)

 Djousse 2008, M 0.15 ( 0.13, 0.17)

 >=1 parent, onset<60y (B)

 Djousse 2008, M 0.10 ( 0.08, 0.12) Jousilahti 1996, M 0.27 ( 0.24, 0.30) Jousilahti 1996, F 0.51 ( 0.46, 0.56)

 >=1 parent, onset<55y (B)

 Djousse 2008. M 0.06 ( 0.05, 0.08)

 Father, onset<60y (B)

 Jousilahti 1996, M 0.20 ( 0.17, 0.23) Jousilahti 1996, F 0.19 ( 0.14, 0.24)

 Mother, onset<60y (B)

 Jousilahti 1996, M 0.10 ( 0.08, 0.12) Jousilahti 1996, F 0.16 ( 0.12, 0.21)

 Both parents, onset<60y (B) Jouilahti 1996, M 0.03 ( 0.02, 0.04) Jousilahti 1996, F 0.03 ( 0.01, 0.06)

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Study Specificity (95% CI)

 >=1 parent (B) Djousse 2008, M 0.69 ( 0.68, 0.70) Sesso 2001, M 0.66 ( 0.65, 0.67) Hippe 1999, M 0.81 ( 0.80, 0.82) Sesso 2001, F 0.66 ( 0.65, 0.66) Hippe 1999, F 0.77 ( 0.76, 0.78)

 Father (B) Sesso 2001, M 0.71 ( 0.71, 0.72) Piros 2000, M 0.98 ( 0.97, 0.99) Sesso 2001, F 0.74 ( 0.73, 0.74)

 Mother (B) Sesso 2001, M 0.91 ( 0.91, 0.92) Piros 2000, M 0.97 ( 0.96, 0.98) Sesso 2001, F 0.88 ( 0.87, 0.88)

 Both parents (B) Sesso 2001, M 0.97 ( 0.96, 0.97) Sesso 2001, F 0.96 ( 0.95, 0.96)

 >=1 parent, onset<65y (B) Djousse 2008, M 0.85 ( 0.84, 0.85)

 >=1 parent, onset<60y (B) Djousse 2008, M 0.90 ( 0.90, 0.91) Jousilahti 1996, M 0.78 ( 0.77, 0.79) Jousilahti 1996, F 0.77 ( 0.76, 0.78)

 >=1 parent, onset<55y (B) Djousse 2008, M 0.94 ( 0.94, 0.95)

 Father, onset<60y (B) Jousilahti 1996, M 0.84 ( 0.83, 0.85) Jousilahti 1996, F 0.83 ( 0.82, 0.83)

 Mother, onset<60y (B) Jousilahti 1996, M 0.92 ( 0.91, 0.92) Jousilahti 1996, F 0.90 ( 0.89, 0.90)

 Bother parents, onset<60y (B) Jousilahti 1996, M 0.98 ( 0.97, 0.98) Jousilahti 1996, F 0.97 ( 0.96, 0.97)

45 
Figure 17. CHD, Cross-sectional Studies, Sensitivity 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; CHD=coronary heart disease; CI=confidence interval 

F=female; M=male 

Figure 18. CHD, Cross-sectional Studies, Specificity 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; CHD=coronary heart disease; CI=confidence interval; 

F=female; M=male 

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Study Sensitivity

 (95% >=1 par

 Sche

CI) ent (B)

uner 2006, M&F 0.24

 Magn

 ( 0.18, 0.31)

o 2008, F 0.38

 Father

 Sche

 ( 0.25, 0.52)

 (B)

uner 2006, M&F 0.19

 Mother 

 Sch

 ( 0.13, 0.25)

(B)

euner 2006, M&F 0.14 (

 >=1 sib

 0.09, 0.20)

ling (B)

 Scheuner 2006, M&F 0.19

 Bother

 Sche

 ( 0.13, 0.25)

 parents (B)

uner 2006, M&F 0.08

 >=1 p

 ( 0.05, 0.14)

arent + >=1 sibling (B)

 Scheuner 2006, M&F 0.07

 >=1 1

 ( 0.04, 0.12)

DR (C)

 Scheuner 2006, M&F 0.70

 >=2 1

 ( 0.63, 0.77)

DR (C)

 Scheuner 2006, M&F 0.16

 >=1 1

 ( 0.11, 0.22)

DR, early onset (C)

 Scheuner 2006, M&F 0.23

 >=1 1 D)

 ( 0.17, 0.30)

DR + >=1 2DR, any age (

 Scheuner 2006, M&F 0.40

 father er,sister,grandmother<65y (E)

 ( 0.33, 0.48)

,brother,grandfather 55y, moth <

 Dodani 2005, M&F 0.60 ( 0.51, 0.69)

 Specificity Study (95% CI) >=

 S F.

1 parent (B)

cheuner 2006, M& 0.87 ( 0.86, 0.88)

 Magno2008, F 0.78 ( 0.72, 0.84)

 F

F.

ather (B)

Scheuner 2006, M& 0.91 ( 0.90, 0.92)

 Mot

06, M&F.

her (B)

Scheuner 20 0.94 ( 0.93, 0.95)

 >=1 sibling (B)

 Scheuner 2006, M&F. 0.95 ( 0.95, 0.96)

 Bot

 S &F.

her parents (B)

cheuner 2006, M 0.98 ( 0.97, 0.98)

 >=1 parent + >=1 sibling (B)

Specificity

 -.5 -.25 0 .25 .5 .75 1

 Scheuner 2006, M&F. 0.98 ( 0.97, 0.98)

 >=1 1DR (C)

 Scheuner 2006, M&F. 0.63 ( 0.61, 0.64)

 >=2 1DR (C)

 Scheuner 2006, M&F. 0.95 ( 0.95, 0.96)

 >=1 1DR, early onset (C)

 Scheuner 2006, M&F. 0.91 ( 0.90, 0.92)

 >=1 1DR + >=1 2DR, any age (D)

 Scheuner 2006,. M&F. 0.82 ( 0.81, 0.84)

 father,brother,grandfather<55y, mother,sister,grandmother<65y (E)

 Dodani 2005, M&F 0.53 ( 0.49, 0.58)

46 
Stroke 

 and one 

H and 

 FH 

ted 

essment. Two25,26 scored highly on all or almost all quality assessment items. 

k of reporting in relation to four of six quality 

 could 

Three studies were included (see Webtable 10, Appendix C) in the stroke analysis, all 

longitudinal in design.24-26 One was conducted in a U.S. populatio Finland,25

in Ja he average followup periods ranged from 5 to 19 years, and analyses focused on 

clinically apparent stroke only. Please see Webtable 14 for the me to ascertain F

strok nd the diagnostic criteria used. 

Family history. Three separate definitions of ‘positive FH’ were examined, all relating to 

parental illn ry B (Table 2). All three studies reported the strength of 

assoc n positive FH and stroke risk in terms of relativ ending on the

defin RRs ranged from 0.73 to 2.17. The data by specific definition are presen

in W , Appendix C. 

P uracy. Figures 19 and 20 present the sensitivity and specificity data for the 

FH d ese studies. The range of sensitivities was 0.05-0.33, and specificities 0.71-

0.98. The range of PPVs were 0.02-0.08 and NPVs 0.96-0.98, for prevalences of stroke up to 3.9 

percent. The AUC for these category B FH definitions was 0.43. 

C e FH definitions available for analysis were restricted to parental FH only, 

and ingle study25 which focused on stroke before the age 

of 60. The data support a negative association between strictness of FH and magnitude of 

sensitivity. However, the PPVs suggest that using any of these FH definitions in isolation from

knowledge of other risk acto ld lead to ov t of ‘FH positive’ individuals being 

wrongly identified as being at higher risk. This is due to the overall low frequency of stroke in 

n,24 one in 

pan. T 26

thods used 

e outcomes, a

ess and all in catego

iation betwee e risk. Dep

ition used, these 

ebtable 4

redictive acc

efinitions in th

onclusion. Th

m data were any of the derived from a s

 f rs, cou er 90 percen

the study populations over the time periods studied. 

Quality ass

The assessment of the third24 was limited by lac

criteria. The possibility of awareness of FH influencing ascertainm troke outcome

not be ruled out, and it was not clear whether the same method of FH collection was applied to 

all pa The rate of attrition over several years of followup was unclear. See Webtable 

13, A

rticipants.

ppendix C. 

ent of s

47 
Figure 19. Stroke, Longitudinal Studies, Sensitivity 

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Study

 Sensitivity

 (95% CI)

 >=1 parent (B)

 Morrison 2000 0.33 ( 0.27, 0.39)

 Jousilahti 1997, M 0.10 ( 0.07, 0.15)

 Kadota 2008, M 0.17 ( 0.11, 0.25)

Jousilahti 1997, F 0.13 ( 0.09, 0.19)

 Kadota 2008, F 0.22 ( 0.15, 0.31)

 Father (B)

 Jousilahti 1997, M 0.05 ( 0.03, 0.09)

Jousilahti 1997, F 0.06 ( 0.03, 0.11)

 Mother (B)

 Jousilahti 1997, M 0.05 ( 0.03, 0.09)

Jousilahti 1997, F 0.07 ( 0.04, 0.12)

Abbreviations: CI=confidence interval; F=female; M=male 

Figure 20. Stroke, Longitudinal Studies, Specificity 

 Study

 Specificity

 (95% CI)

 >=1 parent (B)

 Morrison 2000 0.71 ( 0.70, 0.72)

 Jousilahti 1997, M 0.95 ( 0.95, 0.96)

 dota 2008, M Ka 0.79 ( 0.78, 0.81)

 Jousilahti 1997, F 0.94 ( 0.93, 0.95)

 Kadota 2008, F 0.79 ( 0.78, 0.81)

 Father (B)

 Jousilahti 1997, M 0.98 ( 0.98, 0.98)

 Jousilahti 1997, F 0.97 ( 0.97, 0.98)

 Mother (B)

 Jousilahti 1997, M 0.98 ( 0.97, 0.98)

 Jousilahti 1997, F 0.97 ( 0.96, 0.97)

 -.5 -.25

 Specificity

 0 .25 .5 .75 1

Abbreviations: CI=confidence interval; F=female; M=male 

48 
Diabetes 

Seventeen studies were included in this analysis (see Webtable 15, Appendix C). Five were 

longitudinal27-31 and 12 were cross-sectional.32-43 In addition, the findings of a cross-sectional 

study63 designed expressly to examine different FH definitions are included, although the data 

were not presented in a way which permitted their inclusion in the calculations below. 

Five studies were conducted in U.S. populations,29,31,33,37,40 including one in Japanese 

Americans29 and one in native Alaskans.33 Two studies were conducted in Norwegian 

populations,27,38 and two in the Netherlands.28,41 Single studies were conducted in the United 

Kingdom,30 India,32 Pakistan,42 Nigeria,34 Israel,35 Jordan,43 Greece,36 and Sweden.39 The 

average followup periods for the longitudinal studies ranged from 5 to 22 years, except for one 

study which examined disease risk in offspring (mean offspring age 54 years) of the original 

Framingham cohort.31 Sample sizes ranged from 454 to 64,498. Please see Webtable 15 in 

Appendix C for the methods used to ascertain FH and diabetes, and the diagnostic criteria used. 

Family history. Twenty different definitions of ‘positive FH’ were analyzed, in catego

B-E (Table 2). All studies except one42 reported the strength of association between positiv

and diabetes risk for at least one definition in terms of relative risk, odds ratio, or similar m

Depending on the FH definition used, these ranged from 1.53 to 14.83. The data by specific 

definition are presented in Webtable 4, Appendix C. 

Predictive accuracy. Figures 21 through 24 present the sensitivity and specificity data for 

these definitions of FH. For the longitudinal analyses, the range of sensitivities was 0.02-0.47, 

was 0.02-0.38, and NPVs 0.86-0.99, for underlying 

ries 

e FH 

etric. 

 17) the range of sensitivities was 0.02-0.83 and 

ation 

e 3 while 

gh) and 

and specificities 0.79-1.0. The range of PPVs 

diabetes prevalences up to 16.2 percent. (Webtable 16) The AUC for category C was 0.43. 

For the cross-sectional analyses, (Webtable

specificities 0.44-0.99, for prevalences up to 17.4 percent. The AUC figures for category B, C, 

and D definitions were 0.69, 0.71, and 0.64, respectively. 

A further paper63 reported the results of applying a three-level, FH-based, risk stratific

system to representative U.S. adult survey data. The definitions for the risk strata are 

summarized in Table 3. The overall prevalence of diabetes in the survey population was 6.6 to 

6.7 percent, and ORs of 2.8 and 7.5 were obtained for the moderate and high definitions 

respectively. The FH definitions used for the stratification system are presented in Tabl

the sensitivities, specificities, and predictive values for the increased (moderate plus hi

high risk categories obtained in this analysis are presented in Table 4. 

 

49 
Table 3. Three-le

Stratum D

vel risk stratification system63

efinition 

High ≥ 2 parents and/or siblings with diabetes 

or 

≥ 1 parent or sibling and 2 grandparents with diabetes from the same lineage 

Moderate One 1DR and one 2DR with diabetes 

or 

One 1DR with diabetes 

or 

Two 2DRs with diabetes from the same lineage 

Average No more than one 2DR with diabetes 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative 

Table 4. Discriminatory accuracy metrics associated with risk stratification system63

Risk level Sensitivity Specificity PPV NPV 

All adults (20-85) 

High 0.19 0.94 0.10 0.97 

Moderate + high 0.48 0.73 0.05 0.98 

Older adults (45-85) 

High 0.21 0.93 0.15 0.95 

Moderate + high 0.46 0.70 0.08 0.96 

Abbreviations: NPV=negative predictive value; PPV=positive predictive value 

Conclusion. A large range of FH definitions were examined in these studies, ranging from 

ver

he 

e 

s 

FH may be a useful factor to take into account in triaging individuals for diabetes screening 

(i.e., screening for undetected prevalent disease). The AUC figures suggest that no further 

discriminatory accuracy is obtained by going beyond simple FH definitions, (i.e., limited enquiry 

about 1DRs only). If these findings were replicated, it is possible that meeting a simple FH 

criterion might be sufficient to merit a second stage screening test such as fasting glucose, where 

health care resource constraints present limits to universal screening using clinical tests. Again, 

the underlying prevalence of diabetes in the population should be taken into account as this 

affects the predictive value of any FH definition. 

Quality assessment. The longitudinal studies generally scored highly on quality assessment 

items. For one,30 it was possible that ascertainment of diabetes may not have been blinded to FH 

status, and in two studies28,31 this was not adequately reported. One longitudinal study had more 

than 20 percent attrition over 4 years;28 the participants were elderly men, the attrition is likely to 

have reflected mortality, and a higher rate of diabetes incidence in those lost cannot be excluded. 

y simple to very complex. Almost all indicated a positive association between FH and risk of

diabetes. The studies were very heterogeneous in terms of how diabetes was defined, t

underlying diabetes risk in the population, length of followup, and other characteristics. Taken 

overall, the analyses suggest that using FH to predict future risk of diabetes may have som

utility, and that category B definitions (specifying 1-2 affected relatives) achieve higher overall 

discriminatory accuracy than category C definitions. However, the relationship between diabete

prevalence and PPV should be taken into account. 

50 
Two other longitudinal studies failed to report data on attrition.27,29 Almost all of the crosssectional stu ubject to possible exposure information bias, in that awareness of disease 

status may h , many cross-sectional studies included selfreport of diabetes in their outcom of awareness of FH 

status. Thes osssectional study. The other major quality issue in the cross-sectional studies was the possibility 

of selection bias, throug pling,36,39 and definite or 

p b two studies32,38). See Webtable 18, Appendix C. 

Figure 21. Dia ies, Sensitivity 

dies were s

ave influenced FH reporting. Similarly

e definition, which was not independent

e issues appeared to have been appropriately controlled for, in only one cr

39

h definite or possible non-probability sam

ossible su -optimal participation rates (all but 

betes, Longitudinal Stud

Abbreviations: 1DR=first degree relative; CI=confidence interval; F=female; M=male 

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Sensitivity Study (95% CI) >=1 parent (B)

 Meigs 2000, M&F 0.47 ( 0.40, 0.54)

 Bjornholt 2000, M 0.21 ( 0.15, 0.29)

 Father (B)

 Meigs 2000, M&F 0.24 ( 0.18, 0.30)

 Bjornholt 2000, M 0.07 ( 0.03, 0.13)

 Mother (B)

 Meigs 2000, M&F 0.28 ( 0.22, 0.35)

 Bjornholt 2000, M 0.16 ( 0.10, 0.23)

 Both parents (B)

 Meigs 2000, M&F 0.05 ( 0.03, 0.09)

 Bjornholt 2000, M 0.02 ( 0.00, 0.06)

 >=1DR (C)

 Boer 1996, M 0.22 ( 0.13, 0.34)

 Nakanishi 2003, M 0.21 ( 0.11, 0.33)

 Nakanishi 2003, F 0.28 ( 0.18, 0.40)

 >=1 parent or sibling (C)

 Rahman 2008, M&F 0.19 ( 0.14, 0.23)

 >=1 parent and >=1 sibling (C)

 Rahman 2008, M&F 0.03 ( 0.01, 0.05)

51 
Figure 22. Diabetes, Longitudinal Studies, Specificity 

Abbre egree relative; CI=confidence interval; F=female; M=male 

 Specificity

 Study Specificity

 (95% CI) >=1 parent (B)

 Meigs 2000, M&F 0.79 ( 0.77, 0.80)

 Bjornholt 2000, M 0.90 ( 0.89, 0.92)

 Father (B)

 Meigs 2000, M&F 0.88 ( 0.86, 0.89)

 Bjornholt 2000, M 0.96 ( 0.95, 0.97)

 Mother (B)

 Meigs 2000, M&F 0.89 ( 0.88, 0.91)

viations: 1DR=first d

 -.5 -.25 0 .25 .5 .75 1 1.25

 Bjornholt 2000, M 0.94 ( 0.92, 0.95)

 Both parents (B)

 Meigs 2000, M&F 0.99 ( 0.98, 0.99)

 Bjornholt 2000, M 1.00 ( 0. 9, 1.0 9 0)

 >=1DR (C)

 Boer 1996, M 0.93 ( 0.90, 0.96)

 Nakanishi 2003, M 0.86 ( 0.82, 0.89)

 Nakanishi 2003, F 0.85 ( 0.82, 0.88)

 >=1 parent or sibling (C)

 Rahman 2008, M&F 0.88 ( 0.87, 0.88)

 >=1 parent and >=1 sibling (C)

 Rahman 2008, M&F 0.99 ( 0.99, 0.99)

52 
53 

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

>=parent (B)

Nyenwe 2003, M&F

Annis 2005, M&F

Carlsson 2007, M&F

Mohan 2003, M F&

Father (B)

Annis 2005, M&F

Carlsson 2007, M&F

Mother (B)

Annis 2005, M&F

Carlsson 2007, M&F

>=1 sibling (B)

Annis 2005, M&F

Carlsson 2007 M&F

Brother (B)

Annis 2005, M&F

Carlsson 2007, M&F

Sister (B)

Annis 2005, M&F

Carlsson 2007, M&F

>=1 child (B)

Carlsson 2007, M&F

Bother parents (B)

Annis 2005, M&F

Father or er ( broth B) Carlsson 2007, M&F

Mother or sister (B)

Carlsson 2007, M&F

>=1 1DR (C)

Carlsson 2007, M&F

Bindraban 2008, M&

Shera1

. M

Shera1. F

>=1 parent or sibling (C)

Gikas 2004, M&F

Annis 2005, M&F

Haron 2006, M

Haron 2006, F

>=2 1DR (C)

Carlsson 2007, M&F

>=2 1DR (parents or sibling) (C)

Annis 2005, M&F

>=3 1DR (parents or sibling) (C)

Annis 2005, M&F

>=1 1DR, aunt or uncle (D)

Ebbesson 1998, M&F

Ebbesson 1998, M

Ebbesson 1998, F

>=1 1DR or >=1 2DR (D)

Ajlouni 2008, M&F

>=1 1DR or >=2 2DR (D)

Hilding 2006, M

Hilding 2006, F

>=1 1DR and 1 2DR, same lineage OR 1 1DR OR both parents OR 2 2DR, same lineage (E)

Hariri 2006, M&F

>=2 1DR, same lineage OR >=1 1DR and >=2 2DR, same lineage OR >=3 2DR same lineage (E)

Hariri 2006, M&F

Study

0.29 (0.15, 0.47)

0.47 (0.44, 0.50) 0.23 (0.21, 0.26) 0.30 (0.22, 0.38)

0.18 (0.16, 0.21) 0.09 (0.07, 0.10)

0.37 (0.34, 0.40) 0.19 (0.17, 0.21)

0.38 (0.35, 0.41)

0.12 (0.10, 0.13)

0.24 (0.21, 0.26) 0.12 (0.10, 0.14)

0.27 (0.24, 0.30)

0.10 (0.09, 0.12)

0.02 (0.01, 0.03)

0.09 (0.07, 0.10)

0.13 (0.11, 0.15)

0.21 (0.19, 0.24)

0.43 (0.41, 0.46)

0.83 (0.77, 0.88)

0.27 (0.20, 0.34)

0.21 (0.17, 0.26)

0.64 (0.58, 0.70)

0.64 (0.61, 0.67)

0.33 (0.19, 0.49)

0.40 (0.26, 0.55)

0.12 (0.10, 0.14)

0.27 (0.25, 0.30)

0.12 (0.10, 0.14)

0.37 (0.20, 0.56)

0.33 (0.08, 0.70)

0.38 (0.18, 0.62)

0.58 (0.51, 0.65)

0.79 (0.67, 0.88)

0.71 (0.58, 0.82)

0.73 (0.68, 0.77)

0.45 (0.41, 0.50)

Sens I)

0.29 

itivity (95% C

(0.15, 0.47)

0.47 (0.44, 0.50) 0.23 (0.21, 0.26) 0.30 (0.22, 0.38)

0.18 (0.16, 0.21) 0.09 (0.07, 0.10)

0.37 (0.34, 0.40) 0.19 (0.17, 0.21)

0.38 (0.35, 0.41)

0.12 (0.10, 0.13)

0.24 (0.21, 0.26) 0.12 (0.10, 0.14)

0.27 (0.24, 0.30)

0.10 (0.09, 0.12)

0.02 (0.01, 0.03)

0.09 (0.07, 0.10)

0.13 (0.11, 0.15)

0.21 (0.19, 0.24)

0.43 (0.41, 0.46)

0.83 (0.77, 0.88)

0.27 (0.20, 0.34)

0.21 (0.17, 0.26)

0.64 (0.58, 0.70)

0.64 (0.61, 0.67)

0.33 (0.19, 0.49)

0.40 (0.26, 0.55)

0.12 (0.10, 0.14)

0.27 (0.25, 0.30)

0.12 (0.10, 0.14)

0.37 (0.20, 0.56)

0.33 (0.08, 0.70)

0.38 (0.18, 0.62)

0.58 (0.51, 0.65)

0.79 (0.67, 0.88)

0.71 (0.58, 0.82)

0.73 (0.68, 0.77)

0.45 (0.41, 0.50)

Sensitivity (95% CI)

Figure 23. Diabetes, Cross-sectional Studies, Sensitivity 

-.5 -.25 0 .25 .5 .75 1

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; CI=confidence interval; 
.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

>=parent (B)

Nyenwe 2003, M&F

Annis 2005, M&F

Carlsson 2007, M&F

Mohan 2003, M&F

Father (B)

Annis 2005, M&F

Carlsson 2007, M&F

Mother (B)

Annis 2005, M&F

Carlsson 2007, M&F

>=1 sibling (B)

Annis 2005, M&F

Carlsson 2007 M&F

Brother (B)

Annis 2005, M&F

Carlsson 2007, M&F

Sister (B)

Annis 2005, M&F

Carlsson 2007, M&F

>=1 child (B)

Carlsson 2007, M&F

Bother parents (B)

Annis 2005, M&F

Father or brother (B)

Carlsson 2007, M&F

Mother or sister (B)

Carlsson 2007, M&F

>=1 1DR (C)

Carlsson 2007, M&F

Bindraban 2008, M&

Shera1

. M

Shera1. F

>=1 parent or sibling (C)

Gikas 2004, M&F

Annis 2005, M&F

Haron 2006, M

Haron 2006, F

>=2 1DR (C)

Carlsson 2007, M&F

>=2 1DR (parents or sibling) (C)

Annis 2005, M&F

>=3 1DR (parents or sibling) (C)

Annis 2005, M&F

>=1 1DR, aunt or uncle (D)

Ebbesson 1998, M&F

Ebbesson 1998, M

Ebbesson 1998, F

>=1 1DR or >=1 2DR (D)

Ajlouni 2008, M&F

>=1 1DR or >=2 2DR (D)

Hilding 2006, M

Hilding 2006, F

>=1 1DR and 1 2DR, same lineage OR 1 1DR OR both parents OR 2 2DR, same lineage (E)

Hariri 2006, M&F

>=2 1DR, same lineage OR >=1 1DR and >=2 2DR, same lineage OR >=3 2DR same lineage (E) Hariri 2006, M&F

Study

0.94 (0.91, 0.96)

0.78 (0.77, 0.79)

0.90 (0.90, 0.90)

0.82 (0.79, 0.84)

0.90 (0.90, 0.91) 0.96 (0.96, 0.96)

0.86 (0.85, 0.87) 0.94 (0.94, 0.94)

0.89 (0.89, 0.90) 0.97 (0.97, 0.97)

0.94 (0.94, 0.95) 0.98 (0.98, 0.98)

0.94 (0.93, 0.94) 0.98 (0.98, 0.98)

0.99 (0.99, 0.99)

0.98 (0.98, 0.99)

0.94 (0.94, 0.95)

0.93 (0.93, 0.93)

0.85 (0.85, 0.86) 0.44 (0.41, 0.47) 0.91 (0.89, 0.92) 0.91 (0.90, 0.92)

0.81 (0.79, 0.82) 0.72 (0.71, 0.73) 0.74 (0.68, 0.79) 0.71 (0.67, 0.76)

0.98 (0.98, 0.98)

0.94 (0.93, 0.94)

0.99 (0.99, 0.99)

0.82 (0.78, 0.86) 0.85 (0.80, 0.90) 0.82 (0.76, 0.87)

0.60 (0.57, 0.63)

0.51 (0.49, 0.52) 0.48 (0.46, 0.49)

0.69 (0.67, 0.70)

0.87 (0.86, 0.88)

Specificity (95% CI)

0.94 (0.91, 0.96)

0.78 (0.77, 0.79)

0.90 (0.90, 0.90)

0.82 (0.79, 0.84)

0.90 (0.90, 0.91) 0.96 (0.96, 0.96)

0.86 (0.85, 0.87) 0.94 (0.94, 0.94)

0.89 (0.89, 0.90) 0.97 (0.97, 0.97)

0.94 (0.94, 0.95) 0.98 (0.98, 0.98)

0.94 (0.93, 0.94) 0.98 (0.98, 0.98)

0.99 (0.99, 0.99)

0.98 (0.98, 0.99)

0.94 (0.94, 0.95)

0.93 (0.93, 0.93)

0.85 (0.85, 0.86) 0.44 (0.41, 0.47) 0.91 (0.89, 0.92) 0.91 (0.90, 0.92)

0.81 (0.79, 0.82) 0.72 (0.71, 0.73) 0.74 (0.68, 0.79) 0.71 (0.67, 0.76)

0.98 (0.98, 0.98)

0.94 (0.93, 0.94)

0.99 (0.99, 0.99)

0.82 (0.78, 0.86) 0.85 (0.80, 0.90) 0.82 (0.76, 0.87)

0.60 (0.57, 0.63)

0.51 (0.49, 0.52) 0.48 (0.46, 0.49)

0.69 (0.67, 0.70)

0.87 (0.86, 0.88)

Specificity (95% CI)

Figure 24. Diabetes, Cross-sectional Studies, Specificity

-.5 -.25 0 .25 .5 .75 1

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; CI=confidence 

54 
55 

As

58

2,49,

years,

exam

alm

wit

thma

The asthma and atopic disease analysis was based on 17 publications but only 16 studies are 

presented, four longitudinal,44-46,48 eleven cross-sectional.2,49-58 One of the cross-sectional 

studies59 presented a followup analysis of a random sample of an initial cross-sectional analysis

and was treated as cross-sectional (see Webtable 19, Appendix C); the data for these two studies 

were evaluated separately. Six studies44-46,48,52,57 analyzed data relating to atopic disease in 

general, of which two44,52 also included separate analyses for asthm ing ten studies 

51-56,58,59 presented data relating to asthma alone. 

Three were conducted in U.S. populations,49,52,54 two in German Brazil 

(including two reports of the same cohort),48,58,59 and one each in Q 51 ,

55 Japan,56

Poland,57 Sweden,53 Norway,2

 Spain,50 and the United Kingdom.44 

The four longitudinal studies all followed birth cohorts, one to 12 months,48 o to 2 

44,45 and one to four years.44

Most of the cross-sectional analyses focused predominantly on children and young adults (up 

to 20 years of age), with only two conducted in adult populations, e ma only.2,53 By 

definition, all of the asthma studies examined FH of asthma; one of the longitudinal studies44

also examined FH of atopy as a risk factor for asthma, so for completeness these data were 

included in this report. Please see Webtables 20 through 23 in Appendix C for the methods used 

to ascertain FH and the outcomes of asthma and atopy, and the diagnostic criteria employed. 

Family history. Ten separate definitions of ‘positive FH’ were categories B-D

(Table 2). For the studies of atopy outcome, relative risks/odds ratios ranged from 0.52 to 11.2. 

For the studies of asthma outcome, relative risks/odds ratios from 1.06 to 12.15 were observed. 

The data by specific definition are presented in Webtable 4, Append

Predictive accuracy. Figures 25 through 32 present the sensitiv icity data for 

these definitions of FH, for the outcomes atopy and asthma separately. For the longitudinal 

analyses of atopy, the range of sensitivities was 0.15-0.64, and specificities 0.44-0.91. The range 

of PPVs was 0.25-0.46 and NPVs 0.7-0.84, for atopy prevalences up to 38.6 percent. The AUC 

could not be estimated. 

For the cross-sectional analyses of atopy, the range of sensitivities was 0.23-0.48, and 

specificities 0.56-0.83. The range of PPVs was 0.28-0.52 and NPVs 0.68-0.74, for atopic disease 

prevalences up to 36.2 percent. The data did not permit calculation of AUC figures. 

For the longitudinal asthma analyses, the range of sensitivities was 0.18-0.69 and 

specificities 0.43-0.91. The range of PPVs was 0.17-0.25 and NPVs 0.86-0.89, for an asthma 

prevalence of 15.9 percent. The AUC values could not be estimated -analyses, the 

range of sensitivities was 0.04-0.76 and specificities 0.46-0.99. For studies only, 

the range of PPVs was 0.08-0.51 and NPVs 0.82-0.94, for asthma prevalence up to 19.8 percent. 

For the two adult studies, the PPVs were 0.07 and 0.13 and NPVs 0.96 and 0.98, respectively, for 

prevalences of asthma of 3.1 and 5.5 percent. The AUC values for c C definitions 

were 0.73 (father positive) and 0.77 (mother positive) and 0.66, respectively. 

Conclusion. With the exception of two studies, all of the asthm alyses 

ined prediction of disease in children and young people. Positive FH definitions were 

ost entirely based on affected 1DRs only. The clinical utility of using any FH definition to 

predict future risk onset of asthma or atopic disease in infants or children depends on the 

availability of preventive interventio a u t m y d ational benefits for parents 

h resp tility of choosing of

 and Atopic Disease 

a. The remain

y,45,46 two in 

atar, Turkey

tw

xamining asth

employed, in 

ix C. 

ity and specif

. For the cross

the childhood

ategory B and

a and atopy an

ns, ltho gh here a be e uc

ect to early recognition of symptoms in susceptible children. The u

55 
FH definition as a screening tool for cur

nd risks of other screening or diagnostic m

rent allergy or asthma depends on the availability, cost, 

odalities. 

nt 

d in 

r awareness of disease status influencing 

FH lity of 

ot 

a

Quality assessment. Three of the four longitudinal studies scored well across four of the six 

quality assessment items, the fourth46 meeting three criteria. The issues of concern consiste

across all four were the possibility of ascertainment of atopy or asthma outcome being influenced 

by awareness of FH status, and the possibility for differences in method of capture of FH 

information.46,48 Followup rates were suboptimal for one study,45 and not adequately reporte

another.46 An issue across all the cross-sectional studies was the possibility of awareness of FH 

influencing disease definition or ascertainment, and/o

 reporting. In all, except four reports of three independent studies,51,55,58,59 the possibi

selection bias through non-probability sampling and/or sub-optimal participation rates could n

be dismissed. See Webtable 24, Appendix C. 

Figure 25. Atopy, Longitudinal Studies, Sensitivity 

Abbreviations: 1DR=first degree relative; CI=confidence interval; F=female; M=male; y=years 

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Study Sensitivity

 (95% CI)

 Father (B)

 Tariq 1998, M&F, onset<=4y 0.28 ( 0.23, 0.33)

 Pohlabeln 2007, onset<=2y 0.23 ( 0.19, 0.28)

 Mother (B)

 Tariq 1998 M&F, onset<=4y 0.36 ( 0.31, 0.42)

 Pohlabeln 2007 onset<=2y 0.29 ( 0.25, 0.34)

 >=1 sibling (B)

 Tariq 1998, M&F, onset<=4y 0.45 ( 0.38, 0.53)

 Pohlabeln 2007, onset<=2y 0.15 ( 0.12, 0.19)

 >=1 1DR (C)

 Tariq 1998, M&F, onset<=4y 0.64 ( 0.59, 0.70)

 Pohlabeln 2007, onset<=2y 0.53 ( 0.48, 0.58)

 >=1 of parents, siblings, grandparents (D)

 Lopez 1999 onset<=1y 0.64 ( 0.48, 0.78)

56 
Figure 26. Atopy, Longitudinal Studies, Specificity 

Abbreviations: 1DR=first degree relative; CI=confidence interval; F=female; M=male; y=years 

Figu l Studies, Sensitivity 

 Study Specificity

 (95% CI)

 Father (B)

 Tariq 1998, M&F, onset<=4y 0.75 ( 0.72, 0.78)

 Pohlabeln 2007, onset<=2y 0.81 ( 0.79, 0.83)

 Mother (B)

 Tariq 1998 M&F, onset<=4y 0.67 ( 0.64, 0.70)

 Pohlabeln 2007 onset<=2y 0.78 ( 0.76, 0.80)

 >=1 sibling (B)

 Tariq 1998, M&F, onset<=4y 0.66 ( 0.62, 0.70)

 Pohlabeln 2007, onset<=2y 0.91 ( 0.89, 0.92)

 >=1 1DR (C)

 Tariq 1998, M&F, onset<=4y 0.44 ( 0.40, 0.47)

re 27. Atopy, Cross-sectiona

Abbreviations: CI=confidence interval; F=female; M=male; y=years 

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Pohlabeln 2007, onset<=2y 0.60 ( 0.57, 0.62)

 >=1 of parents, siblings, grandparents (D)

 Lopez 1999 onset<=1y 0.53 ( 0.41, 0.65)

 Sensitivity

 Study (95% CI)

 >=1 parent (B)

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Patrzalek 2003, M&F, onset <=13y 0.31 ( 0.19, 0.46)

 Father (B)

 Alford 2004, M&F, onset 6-7y 0.46 ( 0.37, 0.54)

 Mother (B)

 Alford 2004, M&F, onset 6-7y 0.48 ( 0.40, 0.56)

 Father, childhood (B)

 Alford 2004, M&F, onset 6-7y 0.30 ( 0.22, 0.38)

 Atopy, mother, childhood (B)

 Alford 2004, M&F, onset 6-7y 0.23 ( 0.16, 0.30)

57 
Figure 28. Atopy, Cross-sectional Studies, Specificity 

emale; M=male; y=years 

 Specificity

 Study (95% CI)

 >=1 parent (B)

Abbreviations: CI=confidence interval; F=female; M=male; y=years 

Figure 29. Asthma, Longitudinal Studies, Sensitivity 

Abbreviations: CI=confidence interval; 1DR=first degree relative; F=f

 Specificity

 -.5 -.25 0 .25 .5 .75 1

Patrzalek 2003, M&F, onset <=13y 0.83 ( 0.74, 0.90)

 Father (B)

Alford 2004, M&F, onset 6-7y 0.67 ( 0.61, 0.72)

 Mother (B)

Alford 2004, M&F, onset 6-7y 0.56 ( 0.50, 0.61)

 Father, childhood (B)

Alford 2004, M&F, onset 6-7y 0.81 ( 0.76, 0.85)

 Atopy, mother, childhood (B)

Alford 2004, M&F, onset 6-7y 0.73 ( 0.68, 0.78)

 Sensitivity

 Study (95% CI)

 Mother (B)

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

Tariq 1998, M&F, onset <=4y 0.18 ( 0.12, 0.24)

 Mother, atopy (B)

 Tariq 1998, M&F, onset <=4y 0.41 ( 0.33, 0.48)

 >=1 sibling, atopy (B)

 Tariq 1998, M&F, onset <=4y 0.49 ( 0.39, 0.59)

 >=1 1DR, atopy (C)

 Tariq 1998, M&F, onset <=4y 0.69 ( 0.62, 0.76)

58 
Figure 30. Asthma, Longitudinal Studies, Specificity 

 Specificity

 Study (95% CI)

 Mother (B)

Abbreviations: CI=confidence interval; 1DR=first degree relative; F=female; M=male; y=years 

Figure 31. Asthma, Cross-sectional Studies, Sensitivity 

Abbreviations: 1DR=first degree relative; CI=confidence interval; F=female; M=male; y=years 

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Tariq 1998, M&F, onset <=4y 0.91 ( 0.89, 0.93)

 Mother, atopy (B)

 Tariq 1998, M&F, onset <=4y 0.67 ( 0.64, 0.70)

 >=1 sibling, atopy (B)

 Tariq 1998, M&F, onset <=4y 0.65 ( 0.61, 0.69)

 >=1 1DR, atopy (C)

 Tariq 1998, M&F, onset <=4y 0.43 ( 0.40, 0.46)

 Sensitivity

 (95% CI) Study

 >=1 parent (B)

 London 2001, M&F, onset 9-16y 0.38 ( 0.35, 0.42)

 Father ( ) B London 2001, M&F, onset 9-16y

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 0.19 ( 0.16, 0.22) Garcia-Marcos 2005, M&F, onset 9-12y 0.09 ( 0.06, 0.13) Benar 2005, M&F, onset 6-12y 0.18 ( 0.16, 0.22) Alford 2004, M&F, onset 6-7y 0.21 ( 0.09, 0.39)

 Mother (B) London 2001, M&F, onset 9-16y 0.23 ( 0.20, 0.26) Garcia-Marcos 2005, M&F, onset 9-12y 0.13 ( 0.10, 0.17) Benar 2005, M&F, onset 6-12y 0.22 ( 0.19, 0.25) Alford 2004, M&F, onset 6-7y 0.15 ( 0.05, 0.31)

 >=1 sibling (B)

 Benar 2005, M&F, onset 6-12y 0.63 ( 0.60, 0.67)

 Both parents (B) London 2001, M&F, onset 9-16y 0.04 ( 0.03, 0.05)

 >=1 parent or sibling (B) Melbostad 1998, M&F 0.30 ( 0.24, 0.36)

 Father, childhood (B)

 Alford 2004, M&F, onset 6-7y 0.15 ( 0.05, 0.32)

 Mother, childhood (B)

 Alford 2004, M&F, onset 6-7y 0.09 ( 0.02, 0.24)

 >=1 1DR (c) Montnemery 2000, M&F 0.42 ( 0.37, 0.46) Hu 1997, M&F, onset <=20y 0.46 ( 0.38, 0.53) Hu 1997, M&F, onset <=20y 0.44 ( 0.37, 0.50) Ones 1997, M&F, onset 6-12y 0.16 ( 0.11, 0.21) Chatkin 2005, M&F, onset <=6y 0.76 ( 0.64, 0.86) Chatkin 2005, M&F, onset <=4y 0.68 ( 0.61, 0.75)

 >=1 1DR or grandparent (D) Sugiyama 2002, M&F, onset 13-14y 0.39 ( 0.34, 0.45)

59 
Figure 32. Asthma, Cross-sectional Studies, Specificity 

es 

e 

ood 

ble 

Abbreviations: 1DR=first degree relative; CI=confidence interval; F=female; M=male; y=years

Mental Illness 

 

Two papers contributed to the analysis of mental illness, (see Webtab

longit and one cross-sectional.62 Both presented data on prediction of major depressive 

disorde examined any mood disorder as an ondition, 

consid priate measure in childhood and adolescence. Both examined outcom

accord to 26 years of age and were conduc populations. 

The longitudinal study60 followed up the third generation of a y in which th

grandparents of the participants formed the inception cohort. The second study62 was based on a 

single-age cohort follow d from childhood to age 26, which was treated as

analysis because the FH was ascertained at the followup point. Please see Webtables 26 through 

28 in Appendix C for the methods used to ascertain FH and the outcomes of MDD and m

disorder, and the specifics of the diagnostic criteria used. 

Fa r definitions of ‘positive FH’ were examined, all in category B (Ta

2). For the analyses of MDD outcome, relative risks/odds ratios ra

analysis of mood disorder outcome, a single relative risk of 2.8 was reported. The data by 

specific definition are presented in Webtable 4, Appendix C, along with data on disease 

frequency and predictive values. 

Parental plus grandparental MDD was associated with a the relative risk of 2.80 for any 

mood disorder, and 2.33 for MDD in the third generation.60 Odds ratios of 1.84 and 2.88 were 

found for the association betw rental depress n and sibling depression, respectively, in the 

62

le 25, Appendix C) one 

udinal,60

r (MDD) and one60 also outcome c

ered a more appro

ing to DSM-IV criteria, ted in U.S.

family stud

e a cross-sectional 

mily history. Fou

nged from 1.84 to 2.9. For the 

een pa io

cross-sectional study.

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Study Specificity

 (95% CI) >=1 parent (B)

 London 2001, M&F, onset 9-16y 0.85 ( 0.83, 0.86)

 Father (B) London 2001, M&F, onset 9-16y 0.93 ( 0.92, 0.94) Garcia-Marcos 2005, M&F, onset 9-12y 0.95 ( 0.94, 0.96) Benar 2005, M&F, onset 6-12y 0.93 ( 0.92, 0.94) Alford 2004, M&F, onset 6-7y 0.93 ( 0.90, 0.95)

 Mother (B) London 2001, M&F, onset 9-16y 0.91 ( 0.90, 0.92) Garcia-Marcos 2005, M&F, onset 9-12y 0.92 ( 0.91, 0.93) Benar 2005, M& nset 6-12y F, o 0.91 ( 0.89, 0.92) Alford 2004, M&F, onset 6-7y 0.87 ( 0.83, 0.89)

 >=1 sibling (B)

 Benar 2005, M&F, onset 6-12y 0.70 ( 0.68, 0.72)

 Both parents (B)

 London 2001, M&F, onset 9-16y 0.99 ( 0.99, 1.00)

 >=1 parent or sibling (B)

 Melbostad2

, M&F 0.88 ( 0.87, 0.89)

 Father, childhood (B)

 Alford 2004, M&F, onset 6-7y 0.95 ( 0.93, 0.97)

 8Mother, childhood (B)

 Alford 2004, M&F, onset 6-7y 0.92 ( 0.89, 0.95)

 >=1 1DR (c) Montnemery 2000, M&F 0.84 ( 0.83, 0.85) Hu 1997, M&F, onset <=20y 0.80 ( 0.78, 0.82) Hu 1997, M&F, onset <=20y 0.81 ( 0.79, 0.83) Ones 1997, M&F, onset 6-12y 0.93 ( 0.92, 0.94) Chatkin 2005, M&F, onset <=6y 0.52 ( 0.47, 0.56) Chatkin 2005, M&F, onset <=4y 0.46 ( 0.42, 0.49)

 >=1 1DR or grandparent (D)

 Sugiyama 2002, M&F, onset 13-14y 0.83 ( 0.81, 0.84)

60 
Predictive accuracy. Figures 33 through 38 present the sensitivity and specificity data for 

e of PPVs 

 were 

t at least one 

inal 

 and in 

s could be associated 

nd unnecessary clinical intervention. The uncommon design of this study 

ort) means that the findings cannot automatically be extrapolated to general 

populations, and the ascertainm

e 

nal 

dy) was 

these studies, for the outcomes MDD and mood disorder, respectively. For the longitudinal 

analyses, the range of sensitivities was 0.72-0.83 and specificities 0.40-0.59; for any mood 

disorder, the range of sensitivities was 0.73-0.83 and specificities 0.42-0.

for MDD was 0.14-0.18 and NPVs 0.92-0.95; for mood disorder, nding values

0.24-0.31 and 0.89-0.93. The overall prevalence of MDD for this study was 11.2 percent, and for 

any m .6 rcent. A relatively high proportion of participants me

of the d ive FH (44.1-62.7 percent), reflecting th on of the orig

cohor

The cross-sectional analyses produced sensitivities of 0.12 and 0.24 and specificities of 0.85 

and 0.96, respectively. T e PPVs were 0.33 and 0.45, and NPVs were 0.79 and 0.78, 

respectively, for a prevalence of MDD of 23.2 percent. 

It calculate AUC values for any of the men nalyses. 

C lyses were limited to two studies only, both of which had higher than 

expected frequency of MDD or mood disorder. In one this was a result of study design,60

the oth participant selection bias.62 On the face o dings of the 

longitu to suggest that FH definitions based on parents could predict around 

three fourths of cases of m jor depression or mood disorder in offspring up to the age of 25, 

although the false positive rate is rather high at 50 percent or more. The clinical utility of PPVs 

of around 15 percent for MDD and 25-30 percent for mood disorder depends on the possibility of 

preventive inte ention chi or olesce and e more

aware of an individual’s susceptibility. Whether this level of predictive validity would be 

63. The rang

the correspo

ood disorder was 18 pe

efinitions for posit e constituti

t. 

h

was not possible to tal illness a

onclusion. The ana

er this may reflect f it, the fin

dinal study appear

a

rv in ldhood ad nce, th general net benefits of being 

obtained in lower prevalence populations is questionable, and lower NPV

with stigmatization a

(three generation coh

ent of FH was not typical of a primary care consultation, where 

patient self-reporting would likely be less accurate and less complete. In contrast, the crosssectional study was initially established as a population-based study although fewer than half of 

the original participants were included in the analysis considered here. The prevalence of major 

depression was high (almost a quarter of the study group); like the other study, the method of 

assessing FH was likely m plete and deta ore com iled than would be obtained in a primary car

consultation based on patient self-reporting. For the two FH definitions examined in this study, it

is not possible to draw conclusions regarding the value of using FH alone to screen for presence 

of major depression. 

Taking all of these issues into account, it is difficult to extrapolate the findings to typical 

primary care settings. If similar predictive values were obtained in studies conducted in less 

selected populations and with more typical data collection procedures, parental history of 

depression might offer useful information relating to identifying youth and young adults at risk. 

Quality assessment. The longitudinal study60 scored high across all quality assessment 

criteria, likely reflecting its unusual prospective multi-generational design. The cross-sectio

study62 (which was in fact a cross-sectional analysis of an original prospective cohort stu

assessed as being potentially prone to bias in relation to independence of assessment of FH and 

disease outcome, and selection bias through sub-optimal participation rate at the point the 

analysis was performed. See Webtable 29, Appendix C. 

61 
Figu

Abbreviations: CI=confidence interval; F=female; M=male; MDD=major depressive disorder; y=years 

re 33. MDD, Longitudinal Studies, Sensitivity 

Abbreviations: CI=confidence interval; F=female; M=male; MDD=major depressive disorder; y=years 

Figure 34. MDD, Longitudinal Studies, Specificity 

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Study

 Sensitivity

 (95% CI)

 >=1 parent (B)

 Weissman 2005, M&F, onset <=26y 0.72 ( 0.47, 0.90)

 >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.83 ( 0.59, 0.96)

 >=1 parent and >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.72 ( 0.47, 0.90)

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Study

 Specificity

 (95% CI)

 >=1 parent (B)

 Weissman 2005, M&F, onset <=26y 0.42 ( 0.34, 0.50)

 >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.40 ( 0.32, 0.48)

>=1 parent and >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.59 ( 0.51, 0.68)

62 
Figure 35. MDD, Cross-sectional Studies, Sensitivity 

bbreviations: CI=confidence interval; F=female; M=male; MDD=major depressive disorder; y=years 

 Sensitivity

Abbreviations: CI=confidence interval; F=female; M=male; MDD=major depressive disorder; y=years 

Figure 36. MDD, Cross-sectional Studies, Specificity 

A

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Study (95% CI)

 >

 Reinherz 2003, M&F, onset <=26y

=1 parent (B)

 0.24 ( 0.16, 0.35)

 >=1 sibling (B)

 Reinherz 2003, M&F, onset <=26y 0.12 ( 0.06, 0.21)

 Specificity

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Study (95% CI)

 >=1 parent (B

 Reinherz 2003, M&F, onset <=26y

)

 0.85 ( 0.81, 0.89)

 >=1 sibling (B)

 Reinherz 2003, M&F, onset <=26y 0.96 ( 0.92, 0.98)

63 
Figure 37. Mood, Longitudinal Studies, Sensitivity 

 Sensitivity

Abbreviations: CI=confidence interval; F=female; M=male; y=years 

Figure 38. Mood, Longitudinal Studies, Specificity 

Abbreviations: CI=confidence interval; F=female; M=male; y=years 

 Sensitivity

 -.5 -.25 0 .25 .5 .75 1

 Study (95% CI)

 >=1 parent (B)

 Weissman 2005, M&F, onset <=26y 0.77 ( 0.58, 0.90)

 >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.83 ( 0.65, 0.94)

 >=1 parent and >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.73 ( 0.54, 0.88)

 Specificity

 Study (95% CI)

 >=1 parent (B)

05, M&F, onset <=26y

 Specificity

 -.5 -.25 0 .25 .5 .75 1

 Weissman 20 0.44 ( 0.36, 0.53)

 >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.42 ( 0.33, 0.51)

 >=1 parent and >=1 grandparent (B)

 Weissman 2005, M&F, onset <=26y 0.63 ( 0.54, 0.71)

64 
Question 2: What is the Accuracy of the Family History, 

Under What Conditions Does the Accuracy Vary? 

 General Approach to Evaluating Accuracy 

 reporting of FH) represents the test res

that are true (both positive and negative outcomes). If individuals reporting FH were 100 percent 

accurate, they would correctly identify all relatives with the disease and all those withou

d f metrics may be used to convey accuracy and from these, sensitivity and 

sp e underlying prevalence of the nterest 

population (in this case, a positive FH). We therefore aimed to present sensitivity and

where this is reported in, or could be calculated from, eligible papers as the metric reflecting 

accuracy of self-reporting. Where this was not available, we reported other metrics of accuracy 

s

eporting of FH by the informant” as the “index 

test”, and required that there be comparison to a “gold standard” (representing the real or true 

disease state). We use the term informant to reflect that in some instances the person reporting 

family history may be a proxy respondent who knows the individual for whom family history is 

being evaluated. In this context, sensitivity indicates how accurate informants are at identifying 

relatives who truly ha f rting igh nsiti only a few relative

disease will be reported as diseas reporting is highly specific, only a few 

and 

ults 

t the 

in the 

 specificity 

s with the 

likely that accuracy of 

porting one’s FH will be influenced by factors relating to both the informant and the relatives; 

ical 

ation on 

a 

ntal 

Accuracy of a test (in this case proportion of all

isease. A number o

ecificity are not influenced by th characteristic of i

uch as percent agreement. 

In this systematic review, we considered “r

ve the dis e. I

e-free. Conversely, if 

eas repo is h ly se ve,

relatives who are truly disease-free are misreported as having cancer. It is 

re

the method of capturing the FH data is also an important consideration. 

As there is no clear “gold standard” against which the accuracy of se

evaluated, we decided to accept the following reference standards

disease in the 1DRs and 2DRs, or higher, of the informant: 1) the relative’s medical record, 2) 

c f status by the relative’s physician, 3) death certificate, 4) disease registry, and 5) 

di in question. Not all research da in med

records were elig or this review as we excluded studies that did not 

provide complete accuracy information including those databases that provided inform

t ositives only. Data from these studies would not assist us in understanding 

the true accuracy of respondents providing their FH. 

luated the accuracy of reporting e for dat

extraction, and reported data separately for spouses and genetic relatives. The majority of papers 

(n=16) evaluated accuracy of reporting cancer FH, in persons who had cancer (breast, ovarian, 

colorectal, prostate, lymphoma, melanoma, Ewing’s or mixed cancers) or who were being 

s 12 studies that evaluated accuracy of reporting FH for me

health disorders and these included persons with mood disorders, and 

schizophrenia. The remaining studies evaluated persons with Parkinson’s disease (n=2), persons 

with cardiovascular/hypertension related problems (n=3) or persons with diabetes (n=2) and two 

studies123,124 with populations from longitudinal cohorts that had mixed diseases (diabetes, 

hypertension, cardiovascular disease, and asthm 

lf-reporting of FH is 

 for the presence or absence of 

onfirmation o

rect confirmation by the relative

ible as sources of verification f

tabases that conta

he number of true p

 A total of 37 publications eva FH, were eligibl

creened for cancer. There were 

mixed disorders, 

a).

65 
A

Popu udies 

cer,95-97 prostate cancer,98,99

,

101,102 Ewing’s Sarcoma,103

lym 104 105 106

6

es 

, 33 

nd, for prostate cancer, 47 to 79 percent. 

rom the limited data, it was not possible to draw definitive conclusions about the effects of 

ccuracy of Self-reporting of Cancer FH 

lation. A total of 16 studies evaluated accuracy of reporting cancer FH. These st

recruited informants (probands) with breast cancer,91-94 colorectal can

ovarian cancer,100 mixed cancers (breast, ovarian, colorectal)

phoma, melanoma, and unspecified cancer. 

Nine studies were case series in design and seven were case control studies for probands with 

breast,91 colorectal,95-97 ovarian,100 and prostate98 cancers, and lymphoma.104 In the case-referent 

studies, controls were derived from a range of sources including: the general population (agematched),91,100,104 informants’ spouses and general practice rosters,97 patients who had undergone

colonoscopy but were free of polyps,96 and healthcare administration databases.95,98 The case 

series studies, all collected FH from subjects with cancer who were recruited from specialized 

clinics or registries. One study103 evaluated a sample of deceased relatives of the probands; the 

challenges and potential errors of death certification and registries were the focus of this paper. 

Method of family history collection in informants/probands. The methods of cancer FH

collection varied. Six studies used face to face interviews,91,95,97,99,103,106 six used mailed 

surveys,92,94,96,98,102,105 three used telephone interviews,93,101,104 and one study did not report the 

mode of collection.103 Generally, the specific type of FH questions were not specified, but 

probed information predominately related to degree of the relative. 

Method of disease verification in informants/relative. The methods used to verify 

relatives’ cancer status were primarily multimodal and included: review of medical records 

(including cancer registry) and death registry;92,94,103,106 face to face interview or postal survey of 

relatives;101 postal survey alone;96,105 and contact with physician of deceased relative.99 Three 

studies91,98,102 used medical records alone, and five studies used linkage with cancer registry 

alon 93,95,97,100,104 e.

Disease status was verified in both affected and unaffected relatives in all but five 

studies.91,94,99,102,105 

Study outcomes. Some studies examined only specific cancer family histories, while others 

examined all cancers of interest. Four studies95,97,100,104 examined reporting of any type of cancer 

in relatives while the remaining studies examined cancers that matched that of the probands. 

Tables 5 to 9 show the findings according to the cancer reported in the relatives; we show the 

major cancers identified in (Q1) which include breast, ovarian, colorectal, and prostate (other 

cancers were reported much less frequently). We also include the three studies evaluating 

lym 104 105 10 phoma, melanoma, and unspecified cancers.

In general, specificity across all cancer types and with varying modes of collection was 

consistently high (Tables 5 to 9). For reporting of breast cancer FH, specificities of 91 to 100 

percent were reported; for colon cancer, 91 to 99 percent; for ovarian cancer, 96 to 100 percent;

for prostate cancer, 93 to 99 percent. For lymphoma in relatives, rates were equally high. Two 

studies using population controls and samples from large registries100,104 showed that specificiti

were not altered by the type of cancer reported in relatives; sensitivities were higher for cancers 

at more common sites (for example breast and lung) and lower for less common sites (such as 

leukemia, and lymphoma). The sensitivity varied by the cancer of interest; for reporting of 

relatives with breast cancer, the range was 72 to 95 percent (Tables 5 to 9); for colon cancer

to 90 percent; for ovarian cancer, 42 to 83 percent; a

F

66 
either the method of collecting cancer FH, or the method

status, on sensitivity. 

 of verification of relatives’ reported 

rted 

ietic cancer, and ovarian cancers 

(sam

 with 

r 

t was also difficult to 

com sistent. 

 evaluated the effect of education level using a variety of 

cate es showed 

 ovarian cancer and longer education (>10 years) had decreased 

sen

and 3DRs were identified overall, 

sug t the 

as 

cancer, and were referred to a tertiary level oncology center. Although there are some challenges 

There were five case control studies95,97,98,100,104 that allowed direct comparison of reporting 

accuracy between affected and unaffected informants. In general, there were not significant 

differences between cases and controls with regards to specificity. However, controls repo

lower sensitivities in lymphoma for 1DR with hematopo 104

ple size very low for this cancer).95 In contrast, higher sensitivities were reported in controls 

of relatives with colorectal cancer.95,97

Predictors of accuracy in cancer FH were not consistently evaluated across all the studies 

probing accuracy of self reported cancer FH. Factors related to informants that have been 

evaluated in eligible studies include age, gender, education level, and race, and marital status, 

type of cancer, setting, and insurance status. Factors associated with relatives include, degree of

relation, type of 1DR, age, gender, cancer site/type, and time since diagnosis. We summarize the

factors most frequently evaluated. 

Eight studies91,95-97,100-102,104 evaluated the age of the informant as a predictor of accuracy 

with mixed results. Four studies showed that younger age (<50 and 50-59) was associated

higher specificity,104 or that accuracy increased overall with younger age95,100,101 while one96

showed decreased accuracy with younger age and three found no age effect.91,97,102 No clea

trend emerges, and the type of cancer does not seem to be a factor. I

pare across studies as the manner in which age intervals were categorized was not con

Six studies95-97,101,102,104 examined an association between the informant’s gender and 

accuracy, and no general trend was observed. One study95 suggested higher accuracy in reporting 

relatives with ovarian cancer by women than men. Another study101 suggested lower specificity

of reporting relatives’ cancers by men compared to women. 

Six studies95-97,101,102,104

gorizations; none showed any effect with the exception of two studies. These studi

that for subjects with

sitivities100 for reporting all types combined and breast cancer alone and those with college 

versus high school education had increased accuracy in subjects with breast cancer genetic 

syndromes.94 

Four studies93,94,97,102 examined associations between accuracy and the degree of relative 

whose status was being reported. There was a consistent trend towards increased accuracy of 

reporting relating to 1DR compared to 2DRs or 3DRs. One study97 noted challenges in 

confirming the true status of 2DRs and that fewer 2DRs 

gesting the potential for reporting and confirmation biases. Two studies100,104 showed tha

type of 1DR (for example parent versus sibling) did not affect the high specificity rates and did

not differ for controls or cases; the sensitivities were slightly lower for daughters and sisters of 

controls only.100 

Quality and risk of bias in studies. Webfigure 1, Appendix C details the nine individual 

items used to evaluate risk of bias. We summarize the three primary flaws observed within this 

group of studies. The risk of spectrum bias was high, given that seven of the studies were case 

control in design (indicating the presence of spectrum bias as not representative of range of 

persons within primary care) and the remaining populations had cancer and were recruited from 

specialized settings. For example, one study92 involving informants affected by breast cancer w

restricted to those aged under 40 years, one third of whom were affected by bilateral breast 

67 
in characterizing the spectrum of patients with cancer, some studies included very high risk or 

atypical cancer patients, particularly for breast cancer, rather than patients with all levels of risk 

for 

tely 

aining confirmation) were excluded from the analyses. 

For

 to 24 

ospitals, refusal of access to death certificate information or 

des

n 

as 

. Bias 

bas

ty of studies, suggesting a high risk 

of m

varian 

lized 

er registries which would suggest a high risk of spectrum and selection bias. 

. 

howed that specificities were not altered by the type of cancer reported in 

rela

cancer. 

Partial or differential biases may lead to overestimation of accuracy.157 The disease status

was verified in both affected and unaffected relatives in all but five studies91,94,99,102,105

suggesting that partial verification bias was limited. However, even in the studies that adequa

attempted to evaluate the status of unaffected relatives, many subjects with incomplete data (due 

to linkage problems, or difficulty ascert

 some studies, up to 31 percent92 of relatives could not have their disease status verified. 

Another study103 showed that 11 percent of death certificates were inconclusive and that up

percent of certificates for deceased relatives could not be located.103 Reported difficulties 

included, errors in medical records or pathology reports,92,103 death of relative prior to registry 

formation or other form of record keeping,92 emigration of relatives, incorrect addresses for 

relatives or contact information for h

truction of files,102 and inability to secure consent from the relatives in question.102 

Blinding those verifying cancer status in relatives to the status of the informant was less of a

issue in these cancer accuracy studies. For some studies the use of record linkage strategies w

independent of the status of the relatives.100,104 Lack of blinding could lead to differential 

interpretation particularly where the information contained in medical charts is ambiguous

due to lack of blinding might be less likely to have occurred in studies where verification was 

ed on cancer or hospital registries, and where the diagnoses would have been checked 

through a separate process. However, there are other errors associated with linking databases that 

can lead to misclassification of disease status. Overall, blinding of data collectors to the status of

the relative or the informant was not undertaken in the majori

asking bias. 

Summary. There were 16 studies evaluating accuracy of reporting cancer FH. These studies 

recruited probands with breast cancer,91-94 colorectal cancer,95-97 prostate cancer,98,99 o

cancer,100 mixed cancers (breast, ovarian, colorectal),101,102 Ewing’s Sarcoma,103 lymphoma,104

melanoma,105 and unspecified cancer.106 Subjects were recruited predominately from specia

settings or canc

The methods of cancer FH collection varied as did the questions or tools used to collect FH

Similarly, the methods used to verify relatives’ cancer status were primarily multimodal and 

relatives for whom verification could not be obtained were excluded from analyses. 

Some studies examined only specific cancer family histories, while others examined all 

cancers of interest. Overall, specificity across all cancer types and with varying modes of 

collection was consistently high (>90 percent); sensitivities were lower and generally more 

variable (40 to 90 percent) depending on the cancer types. Two large studies using data linkages

to registries100,104 s

tives; that sensitivities were higher for cancers at more common sites and lower for less 

common sites. Five case control studies showed no significant differences between cases and 

controls with regards to specificity although controls reported lower sensitivities in lymphoma,104

and in colorectal cancer.95,97

Predictors of accuracy in cancer FH were not consistently evaluated across all studies. 

Factors that have been evaluated in eligible studies include informant age, gender, education 

level, and race, and marital status, type of cancer, setting, and insurance status. Factors 

associated with relatives include, degree of relation, type of 1DR, age, gender, cancer site/type, 

68 
and time since diagnosis. No clear trend emerges with age, gender, or education level of the 

informants and the impact on accuracy. There was a consistent trend towards increased accuracy 

of reporting relating to 1DR compared to 2DRs or 3DRs. 

Overall, these 16 studies are at high risk of spectrum and verification biases, which may 

cause an overestimation of accuracy (see Webfigure 1, Appendix C). 

Table 5. Accuracy of self-reporting of FH for cancer in studies that verified the status for breast cancer in 

relatives 

Study 

Population/ 

Design/ Sample 

Size 

Index Test (FH) 

Reference Standard Accuracy 

Breast Cancer in Relatives (Affected and Unaffected) 

 Sensitivity(95%) 

a/a+c; value[ ]

Specificity(95%

d/ b+d; value

) 

 [ ]

AntonCulver93

Consecutive case 

series (n=359): 

Index Test: 

Telephone interview 

54/60; [0.90] 

(0.79-0.96) 

364/369; [0.98] 

(0.97-1.0

19

0) 

96 

U.S. 

female breast 

cancer probands 

from either a 

population based or 

cancer registry 

(1DRs and 2DRs) 

Reference Standard: 

Cancer registry 

Chang104 

2006 

Sweden 

Cases (n=1508): 

lymphoma cancer 

probands from 

cancer registries, 

hospitals, and 

clinics; 

Index Test: 

Telephone interview 

(1DR) 

Reference Standard: 

Cases: [0.73] 

(0.70-0.75) 

Controls: [0.72] 

(0.69-0.74) 

Cases: [0.99] 

(0.98-0.99) 

Controls: [0.99] 

(0.98-1.00) 

Controls (n=1229): 

randomly sampled 

from the population 

Cancer registry 

Kerber95

1997 

U.S. 

Cases (n=125): 

colon cancer 

probands from 

Index Test: 

Personal interview (1DR 

and 2DR) 

Cases: 

11/13; [0.85] 

(0.55-0.98) 

Cases: 

107/112; [0.95] 

(0.90-0.98) 

DARCC study 

health 

administration 

database 

Reference Standard: 

Utah population health 

 κ=0.73 (0.55-

0.90) Controls: 

167/184; [0.91] 

Controls (n=206): 

population based 

from DARCC 

health 

administration 

database 

database; Cancer registry Controls: 

18/22; [0.82] (CI 

NR)^ 

κ=0.58 (0.44-

0.71) 

(CI NR)^ 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; 3DR=third degree relative; 4DR=fourth degree rela

5DR=fifth degree relative; BC=breast cancer; CI=confidence interval; DARCC= Diet, Activity and Reproduction in Colon 

Cancer; FH=family history; GRIS=Genetics Registry System; HBOCS=hereditary breast-ovarian cancer syndrome; LFS=LiFraumeni Syndrome; n=number of subjects; NR=not reported; y=years 

tive; 

69 
Table 5. Accuracy of self-reporting of FH for cancer in studies that verified the status for breast cancer in 

relatives (continued) 

S Population/ tudy Design/ Sample 

Size

Index Test (FH) 

Reference Standard Accuracy 

Bre Cancer in Relatives (Affected and Unaffected) ast 

 Sensitivity(95%) Specificity(95%

a/a+c; value[ ]

) 

d/ b+d; value [ ]

Soe 

2008 

D

C

fe

ynecological 

departments; 

d 

y 

Inde

P

: 

ancer registry 

Case [0.89] 

(0.81-0.97); 

κ=0.85 (0.79-

0.92) 

C

-

0.93) 

 [0.99] 

-1.00) 

gaard100

enmark cancer 

recruited from Reference Standard

ases (n=579 ): 

male ovarian 

probands 

g

Controls (n=1,564):

Population base

from civil registr

x Test: 

ersonal interview (1DR) 

C

ontrol [0.94] 

(0.90-0.98); 

κ=0.89 (0.85

Case

(0.99

Control [1.00] 

(0.99-1.00) 

Ziogas101 

2003 

U.S. 

cer 

iew 

(1DR, 2DR, 3DR) 

ailed GRIS 

eference Standard: 

 from 

relatives or 

3) Death certificates of 

deceased relatives 

188/197; [0.95] 

(0.91-0.98) 

850/873; [0.97] 

(0.96-0.98) 

Probands with

breast (n=670), 

ovarian (n=123) 

and colorectal 

(n=318 both male 

and female) can

from clinic based 

family registries

Index Test: 

Telephone interv

followed by m

pedigree 

R

1) Medical records or 

2) Self-reporting

 

Breast Cancer in Relatives (Affected only) 

E

2000 

Finland 

R) 

hen 

) 

 age 

rality 

t: 

arish 

registries 

2) Hospital records 

3) Cancer registry 

rted

 Co

 100 

 

 94 

 100 

 100 

 87 95 

reola92 Probands (n=N

with breast cancer: 

a) diagnosed w

<40 y 

b) patients with 

bilateral disease, c

unselected for

and late

Index Tes

Mailed questionnaire 

Reference Standard: 

1) Genealogy confirmed 

by church p

 % Cases Repo

Cases Reported

 % 

rrectly 

1DR 95 

2DR 99 96 

3DR 61 

 

 

4DR 23 

5DR 17

Total 

King99 

2002 

U.S. 

Probands with 

prostate cancer 

(n=143) from the 

Index Test: 

Interview 

Accuracy rates: 

Documented (%); 97.6% 

cancer centers Reference Standard: 

Medical records and 

death certificates 

Accurate (%) – 95.0% 

70 
Table 5. Accuracy of self-reporting of FH for cancer in studies that verified the status for breast cancer in 

relatives (continued) 

Study 

Population/ 

Design/ Sample 

Size

Index Test (FH) 

Reference Standard Accuracy

 Sensitivity(95%) Specificity(95%) 

a/a+c; value[ ] d/ b+d; value [ ]

Breast Cancer in Relatives (Affected only)

Parent91

1995 

Canada 

Cases (n=414): 

probands with 

breast cancer 

enrolled in stud

study on nutriti

factors in brea

y on 

onal 

st 

 report

e of dia

s (95 CI, -0.60-1.08) 

ls : -0.03 yrs 

.88=0.82) 

 suggest that more 

 diagnosis 

sociated with >70 yrs of 

respondent, and >10 yrs since 

rela

cancer 

Controls (n=429): 

population based 

Index Test: 

Personal interview (1DR). 

Reference Standard: 

Medical records 

Mean error in

confirmed ag

ed age minus

gnosis 

Cases: 0.24 yr

Contro

%

(95% CI, -

0

Some data to

errors in reporting of age of

are as

diagnosis of the tive 

Schneider94

.S. 

ome of the 

BOCS had breast 

cancer 

s) 

) 

any can s 

BOCS cohort=78% 

ccuracy of any can er diagnoses by 

LFS cohort=52% 

Accuracy of breast cancer 

report=96% 

Accuracy of ovarian cancer 

report=74% 

Accuracy of other LFS related 

cancers=55% 

2004 

U

Two series of 

subjects 

undergoing genetic

testing for having a 

relative with a) LFS 

(n=32), or b) 

HBOCS (n=52) 

S

H

Index Test: 

Self-reporting 

questionnaire (up to 4 

generation

Reference Standard: 

1) Medical records or 2

death certificates 

Accuracy of cer diagnose

H

A c

Sijmons102

s 

Retrospective dex Test: 

rting 

 followed by 

Accuracy rate for cancer: 

Breast 93% 

ther 63% 

2000 analysis of tumor Self-repo

Netherland reports from 

counselees on 120 

families in a 

medical genetics 

clinic 

In

questionnaire

interview 

Reference Standard: 

1) Medical records 

2) Contact with relatives 

Colorectal 89% 

Ovarian 71% 

O

All types 78% 

71 
Table 6. Accuracy of self-reporting of FH for cancer in studies that verified the status for colorectal cancer in 

pulation/ 

D Index Test (FH) 

Re d Accuracy 

relatives 

Study Po

esign/ Sample 

size ference Standar

Colorectal Cancer in Relatives (Affected and Unaffected) 

Sensitivity(95%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ] 

Aitken96 Cases (n=74): Index Te

1995 

Australia er 

3): 

ne 

st: 

 (1DR) 

eference Standard: 

tes 

70/81; [0.86] 219/239; [0.92] 

probands with 

colorectal canc

Controls (n=16

Recruited from 

primary care setting 

who had 

undergo

colonoscopy 

Mailed survey

R

1) Medical record 

2) Death certifica

(0.77-0.93) (0.87-0.95) 

Chang104 

2006 

Sweden 

mphoma cancer 

robands from 

s, 

Index Test: 

Telephone interview 

(1DR) 

ndard: 

s: 

9] 

-1.00) 

.99-1.00) 

Cases (n=1,508): 

ly

p

cancer registrie

hospitals, and 

clinics; 

Controls (n=1,229): 

randomly sampled 

from the population 

Reference Sta

Cancer registry 

In any 1DRs: 

Cases: [0.48] 

(0.46-0.51) 

In any 1DR

Cases: [0.9

(0.99

Controls: [0.53] 

(0.50-0.55) 

Controls: [0.99]

(0

Kerber95

1997 

U.S. 

 study 

ealth 

ase 

Reference Standard: 

cer registry 

13/16; [0.81] (CI 

Controls: 

178/190; [0.94] 

)^ 

Cases (n=125): 

colon cancer 

probands from 

DARCC

h

administration 

database 

Controls (n=206): 

population based 

from DARCC 

health 

administration 

datab

Index Test: 

Personal interview (1DR

and 2DR) 

Utah population health 

database; Can

Cases: 

11/17; [0.65] 

Cases: 

98/108; [0.91]

(0.38-0.86) 

Controls: 

(0.84-0.95) 

NR)^ (CI NR

Abbreviations: 1DR=first degree relative; 2DR third degree relative; BC=breast cancer; 

CI=confidence interval; DARCC= Diet, Activ and Reproduction in Colon Cancer; FH=family history; GRIS=genetics registry 

system; HBOCS=hereditary breast-ovarian cancer syndrome; LFS=Li-Fraumeni Syndrome; n=number of subjects; NR=not 

reported 

=second degree relative; 3DR=

ity 

72 
Table 6. Accuracy of self-reporting of FH for cancer in studies that verified the status for colorectal cancer 

in r (continu

Study Design/ Sample Accuracy 

elatives ed) 

Population/ 

size Reference Standard 

Index Test (FH) 

Colorectal Cancer in Relatives (Affected and Unaffected)

 S

]

ensitivity(95%) 

a/a+c; value[ 

Specificity(95%) 

d/ b+d; value [ ]

Mitchell 

.K. 

): 

actice 

me 

me 

ersonal interview by 

: 

Cancer registry 

30/53; [0.57] 

(0.43-0.69) 

1DRs [0.57] 

(0.43-0.69) 

2DRs [0.271] 

(0.17-0.41) 

Controls: 

1256/1269; [0.99] 

(0.98-0.99) 

1DRs [0.99] 

(0.98-0.99) 

2DRs [0.97] 

(0.99-0.99) 

Controls: 

97

2004 

U

Cases (n=199) 

probands with 

colorectal cancer 

Controls (n=133

recruited from 

general pr

lists in the sa

county and so

spouses of 

probands 

Index Test: 

P

genetics nurse (1DR, 

2DR, 3DR) 

Reference Standard

Cases: 

1DRs [0.53] 

(0.31-0.74) 

2DRs [0.33] 

(0.19-0.51) 

Cases: 

1DRs [0.99] 

(0.98-0.99) 

2DRs [0.99] 

(0.99-0.99) 

Soegaard100 

2008 

Denmark 

: 

d 

ry 

w (1DR) 

Reference Standard: 

y 

 [0.70] (0.54-

0.86); 

κ=0.68 (0.55-

 [0.99] (0.99-

1.00) 

Cases (n=579)

female ovarian 

cancer probands 

recruited from 

gynecological 

departments; 

Controls (n=1,564): 

population base

from civil regist

Index Test: 

Personal intervie

Cancer registr

Cases: 

0.82) 

Controls: 

 [0.69] (0.59-

0.80); 

κ=0.69 (0.60-

0.78) 

Cases: 

Controls: 

 [1.00] (0.99-

1.00) 

Ziogas101 

2003 

U.S. 

ith 

both male 

cer 

sed 

DR) followed by mailed 

GRIS pedigree 

Reference Standard: 

1) Medical records or 

deceased relatives 

4; [0.90] 

(0.84-0.93) 

; [0.97] 

(0.96-0.98) 

Probands w

breast (n=670), 

ovarian (n=123) 

and colorectal 

(n=318 

and female) can

from clinic ba

family registries 2) Self-reporting from 

relatives or 

3) Death certificates of 

Index Test: Telephone 

interview (1DR, 2DR, 

3

174/19 1454/1498

73 
Table 6. Accuracy of self-reporting of FH for cancer in studies that verified the status for colorectal cancer in 

Study

ulation/ 

D Index Test (FH) 

Re d Accuracy 

relatives (continued) 

Pop

esign/ Sample 

size ference Standar

Colorectal Cancer in Relatives (Affected only) 

 Sensitivity(95%) Specificity(95%) 

a/a+c; value[ ] d/ b+d; value [ ]

King99 Probands with 

e 

Index Test: 

rds and 

or c

nted (%) 88

 91.7

2002 

U.S. 

prostate cancer 

(n=143) from th

cancer center 

Interview 

Reference Standard: 

Medical reco

death certificates 

Accuracy rates f olon cancer 

Docume .9% 

Accurate (%) – %

74 
Table 7. Accuracy of self-reporting of FH for cancer in studies that verified the status for ovarian cancer in 

relatives 

Study Population/ 

Design/ Sample 

size 

Index Test (FH) 

Reference Standard Accuracy 

Ovarian Cancer in Relatives (Affected and Unaffected) 

Sensitivity(95%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ] 

Kerber95

U.S. 

ARCC study 

ealth 

administration 

database 

Controls (n=206): 

population based 

from DARCC 

health 

administration 

database 

t: 

ersonal interview (1DR 

rd: 

Utah population health 

database; Cancer registry 

0.99) 

Controls: 

1/5; [0.50] (CI 

NR) 

s: 

/122; [0.96] 

(0.91-0.99) 

Controls: 

201/204;[0.98] 

(CI NR) 

1997 

Cases (n=125): 

colon cancer 

probands from 

D

h

Index Tes

P

and 2DR) 

Reference Standa

Cases: Case

2/3; [0.67] (0.09- 117

Soegaard100 

2008 

Denmark 

Cases (n=579): 

female ovarian 

cancer probands 

recruited from 

gynecological 

departments; 

Controls (n=1,564): 

population based 

from civil registry 

Index Test: 

Personal interview (1DR) 

Reference Standard: 

Cancer registry 

Cases: 

[0.44] (0.27-

0.61); 

κ = 0.57 (0.40-

0.73) 

Controls: 

 [0.42] (0.25-.59); 

κ = 0.47 (0.31-

0.63) 

Cases: 

[1.00] (1.00-1.00) 

Controls: 

[1.00] (1.00-1.00) 

Ziogas101 

2003 

U.S. 

Probands with 

breast (n=670), 

ovarian (n=123) 

and colorectal 

(n=318 both male 

and female) cancer 

from clinic based 

family registries 

Index Test: 

Telephone interview 

(1DR, 2DR, 3DR) 

followed by mailed GRIS 

pedigree 

Reference Standard: 

1) Medical records or 

2) Self-reporting from 

relatives or 

3) Death certificates of 

deceased relatives 

35/42; [0.83] 

(0.69-0.93) 

1017/1028; [0.99] 

(0.98-0.99) 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; 3DR=third degree relative; BC=breast cancer; 

CI=confidence interval; DARCC= Diet, Activity and Reproduction in Colon Cancer; FH=family history; GRIS=genetics registry 

system; HBOCS=hereditary breast-ovarian cancer syndrome; LFS=Li-Fraumeni Syndrome; n=number of subjects; NR=not 

reported 

75 
Table 7. Accuracy of self-reporting of FH for cancer in studies that verified the status for ovarian cancer in 

rel ontinued

Study Design/ Sample rd Accuracy

atives (c ) 

Population/ 

size Reference Standa

Index Test (FH) 

Sensitivity(95%) 

a/a+c; value[ ] 

Specificity(95%) 

d/ b+d; value [ ] 

Ovarian Cancer in Relatives (Affected Only)

King99 

2002 

U.S. 

Probands with 

prostate cance

(n=143) from th

cancer center 

r 

e 

terview 

 Standard: 

edical records and 

y rates for o ncer: 

; A

; 50.0% 

Index Test: In

Reference

M

death certificates 

Accurac varian ca

Documented (%)

100.0%

ccurate (%) – 

76 
Table 8. Accuracy of self-reporting of FH for cancer in studies that verified the status for prostate cancer in 

pulation/ 

D Index Test (FH) 

Re d Accuracy 

relatives 

Study Po

esign/ Sample 

size ference Standar

Prostate Cancer in Relatives (Affected and Unaffected) 

Sensitivity(95%) 

a/a+c; value[ ] 

Specificity(95%) 

d/ b+d; value [ ] 

Chang104 Cases (n=1,508): Index Tes

2006 

Sweden 

er 

linics; 

ontrols (n=1,229): 

randomly sampled 

from the population 

t: 

DR) 

In any 1DRs: 

Controls: [0.60] 

(0.57-0.63) 

In any 1DRs: 

(0.98-0.99) 

Controls: [0.99] 

(0.99-1.00) 

lymphoma canc

probands from 

cancer registries, 

hospitals, and 

c

C

Telephone interview 

(1

Reference Standard: 

Cancer registry 

Cases: [0.47] 

(0.44-0.49) 

Cases: [0.99] 

 

Kerber95

1997 

U.S. 

Cases (n=125): 

colon cancer 

probands from 

DARCC study 

health 

administration 

database 

Controls (n=206): 

population based 

from DARCC 

health 

administration 

database 

Index Test: 

Personal interview (1DR 

and 2DR) 

Reference Standard: 

Utah population health 

database; Cancer registry 

Cases: 

11/16; [0.69] 

(0.41-0.89) 

Controls: 

21/30; [0.7] 

Cases: 

101/109; [0.93] 

(0.86-0.97) 

Controls 

166/176; [0.94] 

Ziogas101 

2003 

U.S. 

Probands with 

breast (n=670), 

ovarian (n=123) 

and colorectal 

(n=318 both male 

and female) cancer 

from clinic based 

family registries. 

Index Test: 

Telephone interview 

(1DR, 2DR, 3DR) 

followed by mailed GRIS 

pedigree 

Reference Standard: 

1) Medical records or 

2) Self-reporting from 

relatives or 

3) Death certificates of 

deceased relatives 

Cases: 

46/58; [0.79] 

(0.67-089) 

Cases: 

557/564; [0.99] 

(0.98-0.99) 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; BC=breast cancer; CI=confidence interval; DARCC= 

Diet, Activity and Reproduction in Colon Cancer; FH=family history; GRIS=genetics registry system; HBOCS=hereditary 

breast-ovarian cancer syndrome; LFS=Li-Fraumeni Syndrome; n=number of subjects; NR=not reported; y=years 

77 
Table 8. Accuracy of self-reporting of FH for cancer in studies that verified the status for prostate cancer in 

rel ontinued

Study Design/ Sample d Accuracy 

atives (c ) 

Population/ 

size Reference Standar

Index Test (FH) 

Sensitivity(95%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ]

Prostate Cancer in Relatives (Affected only)

Zhu98

1999 

U.S. 

7): 

in Group 

orting data 

 death 

certificate 

ancer in Brothers 

: κ = ) 

9y: κ = 0.39 (0.14-0.65) 

ontrols 40-64y: κ = 0.52 (0.16-0.88) 

κ =

Cancer in Fathers 

Cases: 40-64y: κ = 0.76 (-0.55-0.98) 

 65-69y: κ = 0.70 (0.45-0.94) 

y: κ = ) 

9y: κ = 0.51 (0.20-0.82) 

Cases: Probands 

(n=181) with 

prostate cancer 

Controls (n=29

enrolled 

Health Cooperative 

Index Test: 

Self-rep

Reference Standard: 

Medical records,

C

Cases 40-64y

 65-6

 0.85 (0.65-1.00

C

 65-69y: 0.60 (0.31-0.88) 

 

Controls:40-64 0.24 (-0.15-0.62

 65-6

King99 

2002 

U.S. e 

dex Test: 

edical records and 

death certificates 

ccuracy rates for prostate cancer: 

ed (%); A ) – 

Probands with 

prostate cancer

(n=143) from th

cancer center 

In

Interview 

Reference Standard: 

M

A

Document ccurate (%

69.0%; 86.2%

78 
Table 9. Accuracy of self-reporting of FH for cancer in studies that verified the status for other cancers in 

pulation/ 

D Index Test (FH) 

Re d Accuracy 

relatives 

Study Po

esign/ Sample 

size ference Standar

Other Cancer in Relat Affected a ives ( nd Unaffected) 

Sensitivity(95%) 

a/a+c; value[ ] 

Specificity(95%) 

d/ b+d; value [ ] 

Chang104 Cases (n=1,508): Index Tes

2006 

Sweden 

randomly sampled 

from the population 

t: 

erview 

Hematopoietic Hematopoietic 

system cancer 

Any cancer in 

lymphoma cancer 

probands from

cancer registries, 

hospitals, and 

clinics; 

Controls (n=1,229): 

Telephone int

(1DR) 

Reference Standard: 

Cancer registry 

system cancer 

Cases: [0.60] Cases: [0.98] 

(0.57-0.62) (0.97-0.99) 

Controls: [0.38] Controls: [0.99] 

(0.35-0.40) (0.98-0.99) 

Any cancer in 

any 1DRs: 

Cases: 

any 1DRs 

Cases: 

[0.85] (0.83-0.87) [0.89] (0.87-0.91) 

Controls: Controls: 

[0.80] (0.83-0.87) [0.92] (0.90-0.94) 

Mussio106 

rland 

and Italy 

) 

wo 

ifferent sites from 

opulation-based 

cancer registries 

ed 

uestionnaire interview 

2) Cancer registry 

Study A: [0.85] 

Study B: [0.74] 

Study A+B: [0.82] 

Study A: [0.97] 

Study B: [0.97] 

Study A+B: [0.97] 

1998 

Switze

Probands (n=193

with cancer (type 

not specified) 

recruited from t

d

p

Index Test: 

Standardiz

Q

Reference Standard: 

1) Medical records 

Mixed cancers by Mixed Cancers 

study group: by study group: 

Other Cancer in Relatives (Affected Relatives Only) 

Aitken105 

1996 

Australia 

Participants of the 

Queensland 

Familial Melanoma 

Project (913 cases) 

Index Test: 

FH questionnaire 

Reference Standard: 

Medical records 

Medical confirmation of melanoma as 

the diagnosis was obtained for 

623/1040 (59.9%; 95% CI: 56.9-

62.9%). 

A false positive reporting rate by 

cases of 40.1% 

Novakovic103 

1996 

U.S. 

Deceased relatives 

of probands 

(n=122) with 

Ewing’s sarcomas 

Index Test:

Questionnaire 

Reference Standard: 

Medical records and 

death certificates 

% Agreement between self-reporting 

and death certificate 52% (63/122) 

dead relatives 

1DR or proxy spouse: 58% 

2DR: 48% 

% Disagreement between selfreporting and death certificate: 

13% (16/122) dead relatives 

1DR 12% 

2DR 14 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; FH=family history; cancer syndrome; n=number of 

subjects 

79 
Accuracy of Self-Report of Mental Health Disorder FH 

There are u when e cy of reporting FH s with 

mental illnesses. Trad ally, FH is and or control subject (index test) and 

elative (reference standard). However, in 

ental health disorders this is not the typical approach for co n

informants (usually relatives) are sought to establish FH. In ge s t

ing cal s accuracy of s th

st men ar ly usin ria, 

tion o sy s or behaviors in th eing

some situations where a genetic link is presumed, the diagno ted

(i.e., bipolar disorders). The person ave ss 

sufficient insi i presence o ostic sym

similarly, it is n identify the presence of th in re s 

particularly th s cognitive impairment (e.g or the an 

acute phase of the mental health illness (e.g., manic phase of isorder). ts who 

have health information about the proband, their relatives, or u

to establishing a probable diagnosis. There is the added conu t if the re o have 

a mental illness, verification of their own or the probands’ di e

 t elv e aware that t e s. 

9 ic o H colle

er ea A ypic

H wh av s) o ontr

directly about of case

information fr or c situatio

verification of the their own disease status (as 

en rio B and hich FH

f pro h alth disorders. The figure shows that the proband is very 

ften not direc o ase elatives, but rather to 

indicate who might be a possible i ive to con

Scenario B represents the idealized situation where the inform sistance in 

g t iors (rather ) 

ould ass sing” t th disorder i ry 

) and the hi ve F ed by the 

informant; rather their report on th s is to establish a diagnosis 

for several mental health disorders io B assu es that the informant is different 

from the relatives. Scenario C represents the typical situation dies 

where relatives are informants with regards to their own disease status (or presence of key 

symptoms) and that of other relatives. Thus, the dilemma her e usually 

relatives, are present in both the index test (reporting sympto and in verifying the 

dditionally, it is difficult to disentangle the “medical history” of the relative in the index test, 

versus the FH. 

nique challenges 

ition

valuating accura in person

 sought from the prob

verification of the FH is sought by contact with the r

m llecting or verifyi g FH, where 

neral, this raise he problem of 

disentangl accuracy of medi

tal health illnesses

f the presence of

 history versu reporting FH a

g clinical crite

e index test. 

Mo e diagnosed primari necessitating 

confirma mptom e individuals b

sis is substa

 assessed. In 

ntia by a positiv

 the mental illne

e FH 

may not have 

ptoms; 

 who is suspected to h

ght into their condit

 not clear if they ca

e case when there i

on to report the f these diagn

ese symptoms

., dementia)

latives. This i

patient is in

 bipolar d Informan

 both are often so ght as an adjunct 

ndrum tha latives als

sease status is pot ntially 

problematic, he relatives thems

shows a schemat

sons with mental h

ere persons who h

 the disease status

om the probands

es may not b hey also may hav

(index test) is

 a mental illnes

Figure 3 cted in studies 

evaluating p

collect F

f the manner in which F

lth disorders. Scenario represents the t al pathway to 

e the disease (proband

is

r who do not (c ols) are queried

 their relatives. In th the index test is b

 the proxy (who is usually a 

ased on 

ontrol; in an ideal n

relative) is typically not included in the subsequent 

a relative). 

Sc a represents the st

bands with mental

tly solicited for inf

ard approach in w (index test) is collected within 

status of r

families o e

o rmation about the dise

nformant or relat tact for further information. 

ants provide as

establishin the presence of symp oms and behav

e mental heal

 than presence or absence of disease

that w n both the proband (medical histo

(MH)

ist in “diagno

 relatives. Establis

h

ng a positive or negati

m

H is typically not determin

e presence of sympto

. Note that scenar

 then used 

m

 in mental health accuracy stu

e is that informants, who ar

ms or FH)

disease status (reference test). The fundamental difference between the index and reference tests 

is the differing methods used to solicit information about the symptoms or disease status. 

A

80 
Essentially evaluation of accuracy in families with mental health disord

com arison of methods specific to accuracy of reporting of the informant, rather than the 

ers becomes a 

pro wo 

n 

rm 

ith 

ated 

d bipolar affective disorders.116 We have grouped the presentation of the results 

according to these mental health disorder classifications. 

p

band/proxy. As such, the accuracy within these studies represents the accuracy between t

methods of collecting family and medical history from relatives or informants. Although the 

primary interest of this systematic review is on accuracy of reporting by the proband rather tha

the informant and on FH rather than medical history, we recognize that this may not be the no

within this clinical area. We alert the reader to this difference and where possible we attempt to

present data that most likely reflects accuracy of FH rather than MH. 

Figure 39. A schematic representation of collecting FH (Index test) in typical manner (A) and in persons w

mental health disorders (B)(C) 

Abbreviations: FH=family history; MH=medical history 

General study characteristics. Our systematic review identified 12 studies that evalu

the accuracy of collecting FH in persons with mental health disorders. One study collected FH 

but reported only on the accuracy of informant age of onset rather than accuracy of disease status 

in the relatives; as such, the results were not extracted for our research question.118

We grouped the remaining 11 studies based on the primary diagnosis of the probands; in the 

majority of studies, the subjects who were queried about FH were the relatives (predominately 

1DR) of the probands. The disease outcomes for these studies were not restricted to those of the 

probands alone, but tended to include a variety of mental health disorders. Within studies 

evaluating mental health disorders, we include a series of studies with a mixed population of 

elderly with both dementia and depression. 

There were three studies that evaluated relatives of persons with schizophrenia;107-109 three 

studies (four publications) that evaluated relatives of, or persons with, dementia and 

depression;110-113 and, four studies that evaluated relatives of persons with mixed disorders 

including depression and anxiety,114,115 personality disorders alone,117 and combined 

schizophrenia an

Probands/

Controls 

/ Proxy 

Relatives 

FH 

Probands 

/Controls 

MH INFORMANT FH Relatives 

A 

B 

Relative 

Relatives 

(Other) 

FH 

C

81 
Sc

ethod of FH collection in informants/probands. All three studies used a standardized 

tegies 

es for 

arying 

 low (25 

ant (person who reported FH) the diagnosis of an 

affe

rum bias, as 

the 

ome 

k 

 were deceased or who could not participate in 

dire

n bias. 

to the 

hizophrenia and Related Disorders 

Population. Three studies107-109 evaluated relatives (and some informants) of subjects with 

predominately schizophrenia related disorders. Although two of these studies108,109 included 

relatives of controls subjects, the results were not stratified by cases and controls; all three 

studies were therefore case series in design. The informants in each study were based on the FH 

reported by 1DRs although, with the exception of one study,107 the characteristics of these 

relatives were poorly described. 

M

instrument to collect FH (Family History Research Diagnostic Criteria, FH-RDC) and included 

additional standardized diagnostic questions specific to symptoms for schizophrenia and related 

subtype disorders (Table 10). 

Method of verification in informants/relatives. All thr tudies used multiple stra

(termed b te diagnosis (BED)) that included direct interview (including FH and 

diagnostic criteria), medical records when available, and diagnosis by one or more expert 

clin

Study outcomes. All studies evaluated FH for schizophrenia and related subtype disorders; 

one study109 included history of bipolar related disorders and additional categories such as 

alcohol a e 10 det he accu for these studies; the presentation of 

res s those of ary schizophren

all subtypes is not shown). Overall, these three studies show consistently high specificity and 

poorer sensitivity. The sensitivity rates for schizophrenia were moderate (72 to 68 percent) in 

two studies,107,109 but very low in another study (25 percent).108 Related subtypes of 

schizophrenia, for example schizoaffective or atypical psyc , had l tivities (v

from 0 to 55 percent across studies); this suggests that the diagnostic subtype may be a factor 

affecting the estimates of sensitivity. The sensitivity estimate for bipolar disorders was

percent) compared to schizophrenia (68 percent) in the same study.109 

One study109 evaluated factors likely to affect the false positive rate, including subject 

d attributes such as, previous hospitalization, 

ee s

est estima

icians. 

buse. Tabl ails t

 prim

racy outcomes

ults i limited to ia and bipolar disorders (accuracy outcom

hosis ower sensi

(person for whom disease status was given), an

female gender, and older age. For the inform

ctive disorder increased false positives. These findings suggest that difficulties in informant

perceptions of psychiatric behaviors account for the inaccuracies. Another study107 found no 

significant association between the type of 1DR and estimates of accuracy. 

Quality and risk of bias in studies. All three studies were at high risk for spect

informants were predominately relatives of the probands who were recruited from specialized

clinics. In all studies, it was difficult to ascertain which relatives (or informants) refused or were

unable to participate in the study, suggesting high risk of selection bias. With the exception of 

one study,109 there was also a high risk of partial verification bias as it was not clear why s

informants did not receive the reference standard test. Similarly, no attempts were made to see

verification of disease status in relatives who

ct interview.107-109 In two studies107,108 it is likely that FH collection (index test) may have 

been included in the BED (reporting unclear) suggesting the potential for incorporatio

Only one study stated explicitly that the diagnosticians were masked to both the status of the

relative and the proband prior to undertaking the reference test.109 However, masking 

proband status is likely to have minimal impact given that the informants were the subjects of 

these studies. 

82 
Summary. Three case series studies107-109 evaluat

schizophrenia related disorders and bipolar disorder.10

ed relatives of subjects with predominately 

9

 The majority of the sample of informants 

was

ease 

ated 

rs showed lower sensitivities for the later diagnostic group. All 

thre

ion 

tric 

heir 

 combined information in the context of informant pairs (eliminating true familial 

rela

ajor 

ruiting the 

e 

instruments (see Table 

10)

studies showed a 

diff

ent); 

age 

of 

in 

 1DRs of the probands, with some inclusion of control relatives; however, results were not 

stratified for cases and controls. All studies used a standardized test (FH-RDC) to collect FH 

from informants and similarly used standardized psychiatric diagnostic tests to establish dis

within the relatives. Overall, these three studies show consistently high specificity and poorer 

sensitivity; sensitivity varied with the diagnostic subgrouping. The single study109 that evalu

schizophrenia and bipolar disorde

e studies were at high risk for selection and verification biases likely leading to 

overestimation of accuracy. 

Dementia and Depress

Population. Four case series studies110-113 by the same primary author evaluated geria

subjects with dementia and depression. One of these studies110 collected FH of 1DRs and t

spouses and

tionship); as such the results of this study do not reflect accuracy of true FH and the data are 

not presented here. The studies evaluated relatives of patients with Alzheimer’s dementia, m

depression, or both disorders; one study111 included data from the probands’ accuracy of medical 

history as well. Controls subjects and their relatives were recruited in all three studies from the 

general population; the proportion of these varied with each study and not all results were 

stratified for this group. The informants in all studies were predominately 1DRs, but small 

numbers of spouses, 2DRs, and other relatives were also included. The method of rec

relatives was not well described and information on those relatives refusing participation was not 

reported. 

Method of FH collection in informants/probands. FH was collected in all studies using th

FH-RDC instrument and included the use of other diagnostic screening 

. 

Method of disease verification in informants/relatives. Status of the index subjects was

determined using standardized psychiatric instruments to diagnose dementia and depression. 

Study outcomes. The studies evaluating this geriatric group showed that probands/controls 

and informants (predominately 1DR) are more accurate in identifying which relatives do not 

have dementia and depression (specificity range from 74 to 99 percent). All 

erence in sensitivities for diagnosing dementia (21 to 23 percent) compared to depression (34 

to 46 percent) (Table 10); sensitivity of anxiety disorders was lowest across all studies (7 or 8 

percent). 

One study111 estimated accuracy of probands and controls using two different forms of 

interview with the reference standard being the psychiatric criteria interview; similarly, they 

probed relatives using these two different methods. Their findings suggest that probands/controls

have higher sensitivity in reporting dementia FH (82 percent) than do their relatives (23 perc

this difference did not hold for diagnosing depression in family members (sensitivity 46 versus

42 percent). It is difficult to interpret these findings given that so little information other than 

and gender was provided about probands and controls; it is not clear how the cognitive status 

the probands may have influenced these results. Two studies112,113 showed some differences 

sensitivity for relatives of probands (38 percent) compared to relatives of controls (12 versus 16

83 
per

t 

es studies by the same primary author evaluated geriatric 

subjects with dementia, major depression, or both; one study presented informant pair data not 

 not extracted.110 All studies used a standardized test (FH-

 similarly used standardized diagnostic psychiatric tests to 

esta

h 

nia, as these represented a very small proportion of subjects and the outcome of this 

stud

subjects in most studies. In general, it was difficult to disentangle which of the 

info

stan

es 

ded by the use of informant pairs, which may include information from or about 

spo

s 

cent) when diagnosing any psychiatric disorder; specificities were higher (93 to 97 percent) 

and did not differ markedly for this psychiatric outcome. 

Quality and risk of bias in studies. All the studies evaluating relatives and probands with 

dementia and depression were at high risk of spectrum and selection bias; no information abou

relatives that did not participate was provided. A single study111 was not found to be at risk for 

either type of verification bias (partial or differential) or masking bias. The timing of the index

and reference standard tests was not clearly specified in any study. Given the limited number of 

studies, there is a high risk for bias leading to overestimation of accuracy within this group of 

studies. 

Summary. Four case seri 110-113

consistent with FH accuracy and was

RDC) to collect FH in informants and

blish disease within the relatives. All studies within this patient group would suggest that 

probands and informants are better at identifying relatives that do not have depression or 

dementia. However, these studies are at high risk of bias, and the results should be interpreted 

with caution. 

Other Disorders of Mental Health 

 

Population. There were four additional studies that collected FH from populations with

affective or anxiety and depression disorders,114,115 personality disorders,117 and persons wit

bipolar affective disorder, major depression, schizoaffective substance abuse, and substance 

addictions.116 This later study was grouped within the category of mixed disorders rather than 

schizophre

y was any anxiety disorder. All studies were case series in design; however, three studies 

included healthy subjects and their relatives.114,116,117 At least two informants were sought per 

index 114,116,117

rmants were relatives (sharing genetic material) and which were not. 

Method of FH collection in informants/probands. FH was collected in all studies using 

dardized instruments (Table 10). 

Method of disease verification in informants/relatives. In all studies, confirmation of 

disease status was obtained using BED by independent clinicians. 

Study outcomes. Table 10 shows the specific disease outcomes. We have reported those 

with the highest specificity or frequency of diagnoses. The presentation of results in these studi

is confoun

uses of probands or spouses of their relatives. 

A single study117 evaluated the degree of agreement (kappa) between the proband selfreporting versus their relative’s direct reports; this study showed very low agreement (ranging 

from -0.1 to 0.21) suggesting that probands and relatives provide different perspectives on the 

presence of a variety of personality disorders. Another study114 showed widely varying estimate

of sensitivity (from 23.6 to 52.5 percent) depending on the type of anxiety disorder; specificity 

varied from 68 to 89.2 percent. Accuracy of both proband self-reporting and relative selfreporting for mental disorders showed higher sensitivities and lower specificities overall; no 

consistent effect of age and gender or type of relative on accuracy was found. 

84 
Similar results were shown in a study that evaluated anxiety disorders in probands with 

predominately affective disorders; low sensitivities (6 to 19 percent) and higher specificities (97 

to 9

. 

y 

re 

for 

e 

iety and depression disorders, personality disorders, and persons with 

bipolar, major depression, schizoaffective substance abuse, and substance addictions.116 FH was 

er; BED was used in all studies to determine the 

 relatives were more accurate in reporting who 

l 

9 percent) were observed.116 This study also showed some effects of female index subject on

accuracy for some anxiety disorders, suggesting some over-reporting and lower accuracy overall

A final study115 showed lower sensitivities and higher specificities when reporting FH of anxiet

disorders; however the magnitude of the estimates for anxiety disorder sensitivities were almost

triple those reported in another study.116 The authors conclude that the FH tool used is not 

adequate for specialty settings, but suggest that it may be appropriate as a screen in primary ca

settings.115

Quality and risk of bias in studies. Webfigure 2, Appendix C details QUADAS ratings 

these studies. All the studies had high risk of spectrum bias, as the subjects would not be typical

within a primary care setting. As with most studies in the mental health area, it is difficult to 

determine which of the relatives did not have their disease status verified suggesting high risk of 

bias for both partial and differential verification. Masking of the clinicians who determined th

BED was not an issue in these studies. 

Summary. There were four additional studies that collected FH from populations with 

affective or anx 114,115 117

collected in a structured and standardized mann

status of the relatives. In general, probands and

did not have affective or anxiety related disorders; sensitivities for major depression and any

psychiatric disorder were higher than those for anxiety disorders and levels of agreement were

very low for personality disorders. As a group, these studies represent a broad group of menta

health illnesses, and still show a consistent trend with respect to accuracy. However, all these 

studies are at high risk for spectrum and differential biases. 

85 
Table 10. Accuracy of self-reporting of FH for relatives with mental health illnesses 

Study Population/ 

Design/ Sample 

Size 

Index Test (FH) 

Reference Standard Accuracy 

Schizophrenia in Relatives (Affected and Unaffected)

 Sensitivity(95%) 

a/a+c; value[ ] 

Specificity(95%) 

d/ b+d; value [ ] 

Fogelson10

8

200

Case series of Index Test: Schizophrenia: Schizophrenia: 

4 

U.S. 

with adult onset 

schizophrenia 

recruited from 

inpatients public 

psychiatric 

hospitals and adult 

psychiatry 

Interview of at least two 

informants about 1DR 

Reference Standard: 

BED: 

Structured FH face to face 

interview (based on NIMH 

Any psychotic 

disorder: 8/18; 

[0.44] 

Schizoid 

personality 

Any psychotic 

disorder: 

237/237; [1.0] 

Schizoid 

personality 

probands (n=117) Structured FH (FH_RDC) 2/8; [0.25] 246/247; [0.99] 

outpatients. Relative Psychiatric 

History), plus DC (DIS, 

PSE) on 1DR, plus medical 

records (when available) 

disorder: 2/6; 

[0.33] 

disorder: 

244/244; [1.0] 

Li107 

1997 

U.S. 

Case series of 

probands (n=48) 

with schizophrenia 

related disorders 

recruited from 

specialized 

schizophrenia 

center 

Index Test: 

Structured FH (FH-RDC) 

and DC (SRD, SRP) 

telephone interview (1DR) 

Reference Standard: 

SFS method: Face to face 

interviews using the SADS 

and SIDP-R lifetime version 

Psychotic 

SRD:13/18 [0.72] 

Chronic 

Schizophrenia: 

9/13; [0.69] 

Psychotic SRD 

Psychotic 

SRD:18/18; [1.0] 

Chronic 

Schizophrenia: 

182/183; [0.99] 

Psychotic SRD 

on 1DR. Diagnosis made 

by consensus 

and SRP: 31/56; 

[0.55] 

and SRP: 

129/140; [0.92] 

Roy109

1996 

Ireland 

Case series of 

probands (n=402) 

with schizophrenia, 

or major affective 

disorder recruited 

from rural registry 

Controls (n=150) 

recruited from 

county electoral 

registry. IDR were 

the focus of this 

study 

Index Test: 

Structured FH (FH-RDC) 

from >1 informant about 

1DR 

Reference Standard: 

BED: Structured interview 

(SSPD, DSM-III-R), medical 

records, and FH information 

(two diagnosticians made 

final diagnosis) 

Schizophrenia: 

[0.68] 

Schizoaffective 

disorder: [0.23] 

Bipolar disorder: 

[0.25] 

Unipolar 

depression: 

[0.26] 

Schizophrenia: 

[0.994] 

Schizoaffective 

disorder: [0.997] 

Bipolar disorder: 

[0.993] 

Unipolar 

depression: 

[0.958] 

Abbreviations: 1DR=first degree relative; BED=best estimate diagnosis; CIDI=Composite International Diagnostic Interview; 

DAT=Dementia of the Alzheimer type; DC=diagnostic criteria; DIGS=diagnostic interview for genetic studies; DIS=diagnostic 

interview schedule; DSM=Diagnostic and Statistical Manual; Dx=diagnosis; EPQ=Eysenck personality questionnaire; 

FH=family history; FHE=family history for epidemiologic studies; FHIPD=family history interview for personality disorders; 

FH-RDC=family history research diagnostic criteria; GAD=general anxiety disorder; K-SADS-E=Schedule for affective 

disorders and Schizophrenia suitable for children and adolescents - episode; MMSE=Mini-mental state examination; n=number 

of subjects; NIMH=National Institute of Mental Health; OCD=Obsessive compulsive disorder; PD=Parkinson’s disease; 

PDE=personality disorder examination; pts=patients; PSE=present state exam; SAD-LA=Schedule for affective disorders and 

Schizophrenia lifetime anxiety version; SADS=Schedule of affective disorders and Schizophrenia; SCID-NP=Structured clinical 

interview, non–patient version; SE=standard error; SIDAM=structured interview for the diagnosis of Dementia of the Alzheimer 

type, Multi-infarct Dementia and Dementias of other etiology; SRD=Schizophrenia related disorder; SRP=Schizophrenia related 

personality disorder 

^ =for controls

86 
Table 10. Accuracy of self-reporting of FH for relatives with mental health illnesses (continued) 

/ 

Study

Population

Design/ Sample

Size

Index Test (FH)

Reference Standard Accuracy 

Depression and Dementia in Relatives (Affected and Unaffected) 

a

Sensitivity(95%) 

/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ]

Heun112

1996 

f 

r 

 

) 

tia 

Questionnaire) 

rence Standard: 

epressive 

0; 

isorders: 3/45; 

rs: 

ll relatives: 

1/100; [0.310] 

8/74; [0.378] 

epressive 

0.962] 

isorders: 

0.992] 

iatric 

ll relatives: 

79/190; [0.942] 

18/127 [0.929] 

; 

Germany 

Case series o

probands >60 

years with 

depression o

Alzheimer’s 

Dementia 

(n=100) 

Controls (n=40) 

from general 

population.

 

Index Test:

Interviews FH (FH-RDC

plus DC (Dementia Risk 

Questionnaire, Demen

Refe

Interviews that included: 

CIDI, MMSE, and 

SIDAM) 

Dementia: 5/24; 

[0.208] 

D

disorders: 12/3

[0.400] 

Anxiety

d

[0.067] 

Any psychiatric

disorde

A

3

Probands 

relatives: 

 2

Controls 

Relatives: 

3/26; [0.115]

Dementia: 

263/266; [0.989]

D

disorders: 

250/260; [

Anxiety 

d

243/245; [

Any psych

disorders: 

A

1

Probands 

Relatives: 

1

Controls 

Relatives: 61/63

[0.968] 

Heun111

1998 

1998 110

Germany 

series with 

probands >60 

years of age with 

DAT and geriatric and 

uestionnaire) 

e to face interviews 

with DC (CIDI, SIDAM) 

tion: 

dex subjects as 

[0.82] 

/22; [0.23] 

7) 

 of 

y FH 

tion: 

y FH 

Index subjects as 

.92] 

67/173; [0.97] 

 of 

y FH 

ion: 

Case 

depression 

(n=75) 

Index Test: Interview 

using the FH-RDC and 

DC (Dementia Risk 

questionnaire

Dementia Q

Reference Standard: 

Fac

Diagnosis of 

dementia by FH 

informa

In

informants: 

23/28; 

Relatives of pts 

and controls: 

5

p<0.001(t-test; 

d.f.=24

Diagnosis

depression b

informa

Index subjects as 

informants: 

12/26; [0.46] 

Relatives of pts 

and controls: 

5/12; [0.42] 

Index subjects as

informants: 

36/49; [0.74] 

Relatives of pts 

and controls: 

177/183; [0.97] 

p<0.001(t-test; 

d.f.=247) 

Diagnosis of 

dementia b

information: 

informants: 

43/47; [0

Relatives of pts 

and controls: 

1

Diagnosis

depression b

informat

87 
Table 10. Accuracy of self-reporting of FH for relatives with mental health illnesses (continued) 

Study D Re d Accuracy 

Population/ Index Test (FH) esign/ Sample 

Size ference Standar

Mixed Mental Health D ers in Rel isord atives (Affected and Unaffected) 

 Sensitivity(95%) Specificity(95%) 

a/a+c; value[ ] d/ b+d; value [ ]

Lish115 Informants (n=77) 

d 

ants in 

, or 

y 

linics for 

ith 

Index Test: 

time 

rsion for adults 

or the K-SADS-E for 

children 

dult 

ors 

ion/ 

ia: 

674]; 

] 

.905]; 

[0.887]; [0.622]; 

: 

ors 

ia: 

49]; 

750]; 

] 

.686]; 

is: 

.733]; [0.718]; 

1995 

U.S. 

and relatives 

(n=239) selecte

from particip

regional survey

from specialt

university c

persons w

anxiety and 

depression 

FH Screen for 

Epidemiologic Studies 

(FHE) – interview of 

history and pedigree 

collection 

Reference Standard: 

BED: Direct interview 

using the SADS-life

anxiety ve

Informants 

reporting on: 

selves; a

relatives; min

Major 

depress

dysthym

[0.674]; [0.352]; 

[0.000] 

Any affective 

disorder: [0.

[0.364]; [0.000

Any anxiety

disorder: [0

[0.522]; [0.000] 

Any FHE 

diagnosis: 

[0.364] 

Informants 

reporting on

selves; adult 

relatives; min

Major 

depression/ 

dysthym

[0.750]; [0.8

[0.973] 

Any affective 

disorder: [0.

[0.848]; [0.973

Any anxiety

disorder: [0

[0.818]; [0.918] 

Any FHE 

diagnos

[0

[0.735] 

Rougemont6

2008 

Switzerland 5) and 

dex subject pairs 

iblings, parents, 

an adult offspring, 

or spouse). 

Probands (n=621) 

included both 

inpatients and 

outpatients with 

psychiatric 

disorders. Controls 

(n=105) from an 

orthopaedic ward 

were also recruited 

l 

DC and DC (1DR and 

Interview-derived 

diagnoses using the DC 

that included the DIGS, 

GAD, SAD-LA, OCD. 

er: 

ocial phobia: 

] 

er: 

ocial phobia: 

Buecking11

Case series 

evaluating 

informants 

(n=1,62

in

(s

Index Test: 

Structured persona

interview using the FHR

spouses) 

Reference Standard: 

Any anxiety 

disorder: [0.185] 

Panic disord

[0.136] 

S

[0.119] 

GAD: [0.111] 

OCD: [0.059

Any anxiety 

disorder: [0.948] 

Panic disord

[0.991] 

S

[0.981] 

GAD: [0.974] 

OCD: [0.992] 

88 
Table 10. Accuracy of self-reporting of FH for relatives with mental health illnesses (continued) 

Population/ 

Design/ Sample 

Size

Index Test (FH) 

Reference Standard Study Accuracy 

Mixed Mental Health Disorders in Relatives (Affected and Unaffected) continued

Sensitivity(95%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ]

Weissman114

ls 

 these 

 were 

s 

study 

 (1DR) 

: 

nt and blind 

ws using the 

) 

sion 

3.6] (SE 5.4) 

) 

sion 

9.2] (SE 2.2) 

2000 

U.S. 

Case series with 

probands and

informants with 

childhood diagnosis 

of depression 

(n=199) or anxiety 

(n=65) 

Healthy contro

(n=175); from

a total of 289

included in thi

Index Test: 

Brief FH screen

Reference Standard

BED based on 

independe

direct intervie

SAD-LA 

Proband repo

on Relatives 

rts 

Any diagnosis 

[52.5] (SE 3.8) 

Any depression 

[37.9] (SE 4.6

Major depres

[37.9] (SE 5.4) 

Any anxiety 

[2

Proband repo

on Relatives 

rts 

Any diagnosis 

[68.0] (SE 4.5) 

Any depression 

[85.1] (SE 2.8

Major depres

[81.2] (SE 2.8) 

Any anxiety 

[8

Ferro117

1997 

U.S. 

Case series with 

probands (n=224) 

with a variety of 

personality 

disorders; 1DR 

relatives were also 

interviewed. 

st: 

FH 

interview for personality 

disorders (FHIPD) (IDR) 

Reference Standard: 

Structured interview using 

the PDE, SCID-NP, and 

the EPQ 

as

etween PDE and FHIPD, by 

chizoid: 0.19 

l: -0.01 

.28 

c: 0.04 

arcissistic: 0.07 

1 

ls

-aggressive

0.04

Index Te Concordance me ured by kappa 

b

disorder: 

Paranoid: 0.10 

S

Schizotypa

Antisocial: 0

Borderline: 0.15 

Histrioni

N

Avoidant: 0.2

Dependent: 0.05 

Obsessive-compu

Passive

ive: 0.11 

: 0.10 

Self-defeating: 

89 
Accuracy of Self-reporting of Parkinson’s Disease FH 

Population. Two studies evaluated incident cases of Parkinson’s disease120 from a 

inic.119 One was 

 true case con rol study and the other, which did not strati e

classified as a case series. Controls were recruited from comm tch

e, g nicity.119,120 P se

ined us Park sca i M

s (MMSE d iagn in 120

One study120 did provide some info n du son

(mean 8 years with a range from 0 oth y t cs 

of cases.119

Both studi y ts when cases or ece o 

complete the i 119 detailed the proxy parti wed

percent of cases (50 percent for controls) were able to directly respond to the interview. The 

proxy respondents included predominately offspring (cases 58 percent, controls 49 percent) and 

(niece latives-in-law) (cases 33 perc

ethod o in by using 

dardized 120 o a establishing the presence 

of symptoms e Par 11 s included questions 

about the com s.

Method of verification in rela n’s Disease in 

1DRs and screened for the presenc st sequent to this, 

relatives that screened positive were invited for neurological in the case of 

deceased relatives, medical records were reviewed. One stud d informant and 

relative’s self-reporting (stratified by 1DR sibling, parents, o ly a small subgroup 

of relatives was subsequently selected for verification by neu tion and review of 

medical records. Evaluation in both affected and unaffected r h these 

studies. 

Study outcomes and direction of findings. One study,11 DRs 

based on methods of diagnosis that varied from liberal (for example, a single symptom), to 

efinite diagnosis (that included presence of several symptoms and confirmation from a 

specialist). This same study reported the percent agreement between the informants and relatives 

self-reporting as a function of the diagnostic criteria. The findings showed lower kappa values 

for liberal diagnosis criteria (0.41, 95 percent CI 0.23-0.59) than for definite diagnostic criteria 

(0.80, 95 percent CI 0.53-1.00) for any 1DR relative. A similar trend was reported for siblings of 

the informants. The ranges of degree of agreement were different when offspring were probed, 

with kappa varying from 0.69 (95 percent CI 0.48-0.89) for definite diagnosis to 0.74 (95 percent 

CI 0.63-0.85) for liberal criteria. Within this same study, a smaller subsample was selected and 

verification of disease status in the relatives showed that informants (either cases or controls) 

were more accurate in identifying relatives who did not have Parkinson’s disease.119 The 

sensitivity markedly declined as the certainty of disease improved. Although we note that this 

subgroup of informants and their relatives where characterized by fewer controls, the findings 

would suggest neither the gender of the informant nor whether they were cases or controls 

affected this trend. Overall, parents of the informants had better sensitivities than siblings or 

offspring. 

population-based sample, and cases from a Parkinson and movement disorder cl

120 a t fy by proband dis ase status,119 is 

unities and ma ed for 

demographic factors such as ag

ing the Unified 

) in one study119 an

ender, or eth arkinson’s disea in probands was

deter

Statu

m inson’s Disease Rating le and the Min

ostic questions

ental Health 

 established clinical d the other study.

rmation on the media

 to 24 years) while the

 informan

ration of Parkin

er did not specif

’s Disease, 

he characteristi

es allowed for prox

nterview. One study

 controls we

cipants and sho

re d ased or una

 that only 36 

ble t

spouses s/stepchildren, re

f FH collection in

 single question

used to diagnos

position of familie

ent, controls 22 percent). 

 the informants was captured

isted in 

M formants. FH reported

r series of questions that

nson’s disease (Table 

a stan ss

ki ).119 Both studie

tives. Both studies119,120 e

e of disease with diagno

valuated Parkinso

ic questions; sub

 examinations or,

y119 also compare

r offspring); on

rologist examina

elatives was intended in bot

9

 evaluated the accuracy of 1

d

90 
A second study120 also showed that informants were more accurate in re

did not have disease (Table 11). This trend was not different for cases or controls; controls had 

porting relatives who 

the d affected 

98 versus 

, 

studies were case control in original design, they are prone to selection bias 

(QU

h, 

urologist 

exa

positively to either the presence of Parkinson’s Disease or 

to t o 

tests 

n either study (QUADAS item 11). 

the 

ying 

hat 

lowest sensitivity (45 percent controls versus 68 percent in cases). Nor was this tren

by the type of interview (proxy or direct), characteristics of the relative (parents or sibling), or 

the life status (deceased or not). The study findings would suggest that offspring (in comparison

to siblings or parents) had lower sensitivities (60 versus 100 percent) and specificities (

99 percent). 

Quality of studies. Several areas of potential biases were noted within these two studies.

Three biases, selection, verification, and masking, were judged most likely to affect study 

outcomes and are summarized here; all relevant QUADAS items are detailed in Webfigure 3

Appendix C. 

As both 

ADAS item 1). In addition, one study119 did not specify how a subsample, chosen for 

purposes of validation, was selected and showed unequal number of controls (only 20 controls

and 76 cases). Both studies attempted to evaluate affected and unaffected relatives and as suc

risk of partial verification bias was low (QUADAS item 5). Both studies used multiple methods 

to verify the disease status of the relatives (for example, self-reporting of relative and ne

mination) and these were clearly described. However, both studies were prone to differential 

verification bias, as confirmation of deceased or incapacitated relatives’ necessitated different 

reference standard methods (QUADAS item 6). In addition, both studies asked additional 

questions for those who responded 120

hose who had at least one Parkinson’s symptom; informants and relatives who responded n

or who had no positive symptoms were assumed to be disease free. 

The risk of biasing due to lack of blinding during interpretation of the index or reference 

was not consistent across studies. Although a high proportion of proxy informants (63 percent 

were 1DR) were used in one study, these 1DRs were excluded from further data collection;120 the 

second study did not clarify any exclusions due to participation as proxy informant (QUADAS 

item 10).119 The data collectors were not blinded for all methods used to verify the status of the 

relative i

Summary. Two studies evaluated accuracy of reporting in persons with Parkinson’s 

disease.119,120 Both studies used multimodal strategies for establishing disease status within 

1DRs. One population-based study showed that informants were more accurate at identif

relatives without the disease (specificity); this study also showed that cases were more accurate 

than controls (68 percent versus 45 percent) in correctly identifying relatives with Parkinson’s 

disease (sensitivity).120 A second study119 also showed that informants were more accurate at 

identifying relatives without Parkinson’s disease for the diagnostic certainty categories of 

“definite/ probable” and “definite”. Their findings suggest that the degree of certainty of 

diagnosing Parkinson’s disease, impacts the level of agreement between informants and relatives 

self-reporting of disease status. This trend in accuracy was not affected by the type of interview,

type of 1DR, or the life status of the relative. 

Given that there is risk of bias in more than one area within so few studies, we judge t

there is high risk of bias affecting the interpretation of the results, likely causing an 

overestimation of accuracy. 

91 
Ac

nd self-administered questionnaire123,124 were used to capture FH (Table 11). 

as 

s 

 percent) versus siblings (72 percent); specificities (98 percent) were not altered 

by rs and 

ences 

nly 

not have the disease. Quality of these four 

stud

s 

rch 

questionnaire involving relatives.121,124,126

Study outcomes and direction of findings. Hypertension: Four studies reported on 

hypertension within relatives; from these, two studies123,126 showed sensitivities (0.57–0.60 

percent) and specificities (0.90–0.96 percent) for reporting of disease in mothers was higher than 

curacy of Self-reporting of Diabetes FH 

Population. Four studies evaluated the accuracy of reporting FH of diabetes on subjects with 

diabetes,122 and hypertension or diabetes121 and from cohorts with mixed diseases.123,124 The 

study designs used included case series,121 cross-sectional,122 and longitudinal cohorts.123,124

Method of FH collection in informants/probands. Face to face interview121 telephone 

interview122

 a

Method of disease verification in informants/relatives. Disease status of the relatives w

verified with clinical assessment,121 and interview or questionnaire.121-124

Study outcomes and direction of findings. One study124 showed differences in sensitivitie

for parents (87

type of 1DR. Another study123 compared accuracy for reporting for mothers and fathe

showed slightly higher sensitivities for mothers (56 versus 65 percent); there were no differ

in specificities (97 percent) (Table 11). Another study121 showed high specificity (98 percent) 

with lower sensitivity (53 to 61 percent ) for both methods of verification (either interview with 

the sibling or with clinical data). One study122 reported only concordance values varying by 

paternal grandparents (kappa=0.76) and mother (kappa=0.90). 

 Quality and risk of bias in studies. Webfigure 4, Appendix C shows the QUADAS rating 

for these studies. All studies included subjects with the disease, but two studies123,124 selected 

subjects that were representative of primary care and therefore less prone to spectrum bias. O

one study121 was at risk for differential verification bias as not all records or death certificates 

were found for all potential subjects. Masking bias was difficult to assess in most studies for the 

reference standard. 

Summary. Four studies evaluated the accuracy of reporting FH of diabetes in subjects with 

diabetes,122 hypertension or diabetes,121 and from cohorts with mixed diseases.123,124 FH was 

captured in a standardized manner and verification included contact with relatives, selfadministered questionnaire, or clinical assessment. Overall, specificities ranged from 97 to 98 

percent and sensitivities varied from 53 to 87 percent. When reporting FH of diabetes, subjects 

are more accurate at identifying relatives that do 

ies would suggest that the risk of bias was low. 

Accuracy of Self-reporting of Cardiovascular Diseases FH 

Population. Six studies evaluated healthy students,126 subjects with hypertension,125

hypertension or diabetes,121 definite or probable myocardial infarction (MI),128 and two studie

evaluated probands from longitudinal study cohorts with and without a variety of diseases 

including stroke, hypertension, MI and diabetes. Three studies were case series in 

design,121,125,126 two were longitudinal designs,123,124 and one case control.128

Method of FH collection in informants/probands. A variety of methods were used to 

capture FH (Table 11) but all were well described and standardized. 

Method of disease verification in informants/relatives. Disease status was verified with

medical records,123,125 death records,128 clinical assessment,121,123 records from resea

database,123 and interview or 

92 
those for fathers (sensitivity 0.44-0.74, specificity 0.88-0.89

in undergraduate volunteers showed that reporting paternal h

 percent). In contrast another study126

ypertension was more sensitive (74 

per

sus 

91)

g MI, showed better 

agr

c 

ecificities ranged from 59 to 83 

aluated the impact of proband characteristics, and mixed results were shown. 

the 

r 

ith 

y showed higher sensitivities (85 and 90 

percent) for 1DRs; 1DRs of controls tended to have the highest sensitivities (90 and 95 percent). 

ities (65 to 80 

s accurately for 

all 

ting 

 to 

in 

. 

ith 

e 

cent) than for maternal disease (60 percent), but specificities were still high (89 to 96 percent) 

(Table 11). Another study124 compared accuracy of reporting of hypertension in parents and 

siblings, and showed lower sensitivities (56 versus 76 percent) but higher specificities (84 ver

 for siblings. A single study121 showed the opposite trend with higher sensitivities (90 

percent) and lower specificities (55 to 78 percent). 

Heart disease: Four studies evaluated accuracy of reporting cardiovascular disease123,124,128

MI,123,125 and stroke.123 One study125 evaluating concordance with reportin

eement for fathers than mothers (Table 11). Another study123 showed accuracy of reporting of 

disease in mothers relative to fathers (Table 11); generally specificities (91 to 98 percent) were 

higher than sensitivities. Sensitivities were lowest for stroke (42 to 51 percent) and highest for 

death by heart disease (72 to 81 percent) with variable differences in parental gender due to the 

disease endpoint. A similar trend with higher specificity was shown in another study124 and no 

appreciable differences were observed when reporting on disease in parents or in siblings. In 

contrast, a case control study128 showed higher sensitivities (83 to 95 percent) for both cardia

heart disease and all heart disease for both cases and controls; sp

percent. 

Other factors affecting accuracy: One study evaluated the impact of differing positive family 

history definitions with broad classification (for example heart attack at any age) or narrower 

parameters (for example, heart attack <55 years).123 This study showed that broader definitions

of FH increased true positives, and positive predictive values and sensitivities. 

Three studies ev

One study123 showed age of the proband did not impact accuracy. Another study124 showed that 

older adults (55 or older) had a greater probability of disagreement, however this varied with 

four diseases evaluated. Similarly, there were some variations for the type of relative; fo

example older probands with cardiovascular disease had greater probability of disagreement w

reporting disease in siblings and spouses than in parents. Across all diseases evaluated, no clear 

trend emerges. 

Comparison of cases and controls within one stud 128

For 2DR relatives, the pattern between sensitivities (76 to 80 percent) and specific

percent) was less pronounced. In another study probands with disease reported les

relatives and for all disease types except cardiovascular disease.124 

In two other studies the presence of a risk factor for a disease123 or having the disease128 did 

not affect estimates of accuracy relative to those that were free of the disease or risk factor. 

Quality and risk of bias in studies. Webfigure 5, Appendix C shows the QUADAS ra

for these studies. Three of the studies123,124,128 had large population based samples representative 

of primary care. Relative to these studies, those with smaller sample sizes studies were prone

differential bias. It was difficult to assess the risk of masking bias for the reference standard 

most studies. Criteria for subject selection and withdrawals were well described in most studies

Summary. Six studies evaluated accuracy of reporting hypertension,123-125 hypertension or

diabetes,121 definite or probable MI,123,128 and stroke123 in their relatives, predominately 1DR. FH 

was captured in a standardized manner for all studies and verification included contact w

relative (interview or postal questionnaire), or death certificate or medical record. All but on

93 
study128 reporting sensitivity and specificity generally showed lower sensitivities across 

hypertension and other cardiovascular outcomes. 

94 
Table 11. Accuracy of self-reporting of FH for relatives with other diseases 

Study Population/ 

Design/ Sample Index Test (FH) 

Size Reference Standard Accuracy 

Parkinson’s in Relatives (Affected and Unaffected) 

 Sensitivity(95%) 

a/a+c; value[ ] 

Specificity(95%) 

d/ b+d; value [ ] 

Elbaz120 

2003 

U.S. 

1) Cases: 

probands (n=133) 

with Parkinson’s 

disease accrued 

from medical 

records-linkage 

system of state 

county. 

2) Controls 

(n=119): from local 

community 

3) Proxy informants 

were primarily 1DR 

for deceased and 

incapacitated 

subjects 

Index Test: Standardized 

FH (and DC) telephone 

interview 

Reference Standard: 

Structured FH (and DC) 

telephone interview of 

1DR followed by clinical 

examination (positive 

screen only) 

Cases: 

17/25; [0.68] 

(0.47-0.85) 

Controls: 

05/11; [0.45] 

(0.17-0.77) 

Cases: 

622/630; [0.99] 

(0.98-0.99) 

Controls: 

499/500; [1.0] 

(0.99-1.0) 

Marder119 

2003 

U.S. 

1) Cases: 

probands (n=304) 

with non-demented 

PD recruited from 

specialized centre 

2) Community 

controls (n=232) 

3) Proxy Informants 

(for 1DR who could 

not be interviewed 

or were deceased) 

Index Test: 

Personal or telephone 

interview (1DR) 

Algorithm to assign level 

of certainty to the 

diagnosis 

Reference Standard: 

1) Telephone interview 

with relatives followed by 

neurological examination 

2) Medical record review 

(for deceased relatives) 

By certainty of 

PD diagnosis 

(Dx): 

Liberal Dx: 22/22; 

[1.0] 

Conservative Dx: 

21/22; [0.955] 

Definite or 

probable Dx: 

16/22; [0.727] 

Definite Dx: 

12/22; [0.545] 

By certainty of 

PD diagnosis 

(Dx): 

Liberal Dx: 

98/104; [0.942] 

Conservative Dx: 

100/104; [0.962] 

Definite or 

probable Dx: 

103/104; [0.99] 

Definite Dx: 

103/104; [0.99] 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; CHD=coronary heart disease; CI=confidence interval; 

DC=detailed family composition; Dx=diagnosis; FH=family history; MI=myocardial infarction; n=number of subjects; 

PD=Parkinson’s Disease; y=years 

95 
96 

Tab ccuracy g of FH fo er diseases (continued) 

Study Design/ Sample Accuracy

le 11. A of self-reportin

Population/ 

r relatives with oth

Size Reference Standard 

Index Test (FH) 

Diabetes in Relatives (Affected and Unaffected)

Sensitivity(95%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ]

Bensen

nth 

 of the 

ersonal history 

) 

Sibling 

0.72 (p=0.021) 

κ=0.72 

Sibling 

0.98 (p=0.002) 

κ=0.72 

124

1999

U.S. 

Sample from the 

NHLBI Family 

Heart Study 

(n=3020) selected

randomly and no

randomly 

(oversampled wi

CHD). Some

probands had 

CHD, diabetes, 

hypertension, and 

asthma 

Index Test: 

Mailed questionnaire 

including p

and FH (1DR and 

spouses) 

Reference Standard: 

Same questionnaire as 

probands

Diabetes 

Proband vs 

Parent 

0.87 (p=0.032

κ=0.83 

Proband vs 

Diabetes 

Proband vs 

Parent 

0.98 (p=0.005) 

κ=0.83 

Proband vs

Murabito123

2004 

U.S. 

d 

Index Test: 

Structured questionnaire 

including personal history 

father and 

m 

t contained 

Diabetes 

Within Fathers 

 Mothers 

Diabetes 

Within Fathers 

 Mothers 

Participants from 

Framingham 

Offspring study 

(males = 791,

females 837) Some

probands had high 

blood pressure, 

diabetes, high 

cholesterol, heart 

attack <55 yrs, an

stroke < 65 yrs. 

and FH (1DR 

mother separately) 

Reference Standard: 

Research database 

(original Framingha

cohort) tha

medical records of both 

parents 

56 (50-62) 

Within

65 (59-71) 

97 (96-98) 

Within

97 (96-98) 

Bochud121

2004 

Switzerland 

ational register of 

ypertension 

(n=384) and 

diabetes (n=404) 

eference Standard: 

Clinical assessment 

rt of 

] 

-

rt of 

] 

6-

Case series of 

families selected 

from an ongoing 

n

h

who attended 

primary health care 

centers 

Index Test: 

Structured questionnaire 

including personal history

and FH (1DR) 

R

Diabetes 

Sibling repo

history: [0.534

(0.433-0.633) 

Clinical status: 

[0.614] (0.501

0.719) 

Diabetes 

Sibling repo

history: [0.982

(0.971-0.989) 

Clinical status: 

[0.978] (0.96

0.986) 

Karter

1999 

U.S. 

Subgroup of 

African American 

(and non-Hispanic) 

participants 

(n=206) from 

population 

(n=43,533) survey 

study; probands 

had diabetes and 

one additional 

relative affected 

Index Test: Telephone 

interview – FH 

questionnaire (1DR, 2DR)

Reference Standard: 

Telephone interview with 

relative to complete 

pedigree 

Overall concordance [κ]: 

Diabetes in paternal grandfathers: 

=0.76 

Diabetes in mother: =0.90 

122
Table 11. Accuracy of self-reporting of FH for relatives with other diseases (continued) 

Study Population/ 

Design/ Sample 

Size

Index Test (FH) 

Reference Standard Accuracy 

 Sensitivity(95 Specificity(95%) 

%) d/

a/a+c; value[ ]

 b+d; value [ ]

Hypertension, Stroke, and Cardiovascular Disease in Relative d and Un s (Affecte affected) 

Bochud121

Switzerland 

n 

d FH 

ypertension 

eport of 

913) 

s: 

0.866-

Hypertension 

S of 

hi

(0

C

[0.554] (0.514-

0.

2004 

Case series of 

families selected 

from an ongoing 

national register of 

hypertensio

(n=384) and 

diabetes (n=404) 

who attended 

primary health care

centers 

Index Test: Structured

questionnaire including 

personal history an

(1DR) 

Reference Standard: 

Clinical assessment 

H

Sibling r

history: [0.89] 

(0.864-0.

Clinical Statu

[0.898] (

0.924) 

ibling report

story: [0.776] 

.732-0.816) 

linical Status:

595) 

Murabito

2004 

U.S. 

123

estionnaire 

on 

ithin Mothers 

holesterol 

Within Fathers 

Hyperte n 

Within Fathers

[0

Within Mothers 

[0.90] (88-92) 

H erol 

Within Fathers 

[0.92] (90-94) 

Within Mothers 

[0

Participants from 

Framingham 

Offspring study 

(males=791, 

females 837) Some 

probands had high 

blood pressure, 

diabetes, high 

cholesterol, heart 

attack <55 yrs, and

stroke <65 yrs 

Index Test: 

Structured qu

including personal history 

and FH (1DR father and 

mother separately) 

Reference Standard: 

Research database 

(original Framingham 

cohort) that contained

medical records of both 

parents

Hypertensi

Within Fathers 

[0.44] (41-47) 

W

[0.57] (54-60) 

High 

C

[0.19] (17-21) 

Within Mothers 

[0.18] (16-20) 

nsio

.88] (86-90) 

igh Cholest

.95] (93-97) 

Bensen124

1999 

U.S. 

 with 

s, 

and 

tory 

and FH (1DR and 

spouses) 

aire as 

 vs 

arent 

.76 (p=0.021) 

κ=0.58 

ibling 

H

P s Parent 

0.84 (p=0.018) 

κ=0.58 

Proband vs Sibling 

0.006) 

κ

Sample from the 

NHLBI Family 

Heart Study 

(n=3020) selected 

randomly and nonrandomly

(oversampled

CHD). Some of the

probands had 

CHD, diabete

hypertension, 

asthma 

Index Test: 

Mailed questionnaire 

including personal his

Reference Standard: 

Same questionn

probands 

Hypertension 

Proband

P

0

Proband vs 0.91 (p=

S

0.56 (p=0.013) 

κ=0.47

=0.47 

ypertension 

roband v

97 
Table 11. Accuracy of self-reporting of FH for relatives with other diseases (continued) 

D Re d Accuracy Study Population/ Index Test (FH) esign/ Sample 

Size ference Standar

 Sensitivity(95

a/a+c; e[ ]

Specificity(95%) 

%) d

 valu

/ b+d; value [ ]

Hypertension, Stroke, and Cardiovascular Disease in Relatives (Affected and Unaffected) 

France126 Undergraduate Index Test: FH Hypertension Hypertension

1998 

U.S. 

student voluntee

(age 19 to 50 y) 

(n=493) 

participated in a 

health survey 

rs l 

eference Standard: FH 

biological parents; 

telephone interview 

aternal aternal history: 

9] 

questionnaire on parenta

blood pressure 

information (1DR) 

R

questionnaires on blood

pressure mailed to 

M

history: [0.604] 

Paternal 

history: [0.737]

Both parents 

combined: 

[0.682] 

M

[0.963] 

Paternal history:

[0.890] 

Both parents 

combined: [0.92

Murabito123 nts from 

y 

me 

rt 

Index Test: 

estionnaire 

eference Standard: 

Heart Attack 

ithin Mothers 

eath by heart 

e 

ithin Fathers 

2 (65-79) 

2 (32-52) 

rs 

) 

Heart Attack 

ithin Mothers 

eath by heart 

ithin Mothers 

troke <65 yr 

6 (95-97) 

2004 

U.S. 

Participa

Framingham 

Offspring stud

(males = 791, 

females 837) So

probands had high 

blood pressure, 

diabetes, high 

cholesterol, hea

attack <55 yrs, and

stroke <65 yrs. 

Structured qu

including personal history 

and FH (1DR father and 

mother separately) 

R

Research database 

(original Framingham

cohort) that contained

medical records of both

parents

<55 yr 

Within Fathers 

74 (64-84) 

W

Too few events 

D

diseas

W

81 (77-85) 

Within Mothers

7

Stroke <65 yr 

Within Fathers

4

Within Mothe

51 (40-62

<55 yr 

Within Fathers 

91 (90-92) 

W

Too few events 

D

disease 

Within Fathers 

86 (84-88) 

W

91 (90-92) 

S

Within Fathers

9

Within Mothers 

98 (97-99) 

98 
Table 11. Accuracy of self-reporting of FH for relatives with other diseases (continued) 

Study Population/ 

Design/ Sample 

Size

Index Test (FH) 

Reference Standard Accuracy 

Sensitivity(95

%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ]

Hypertension, Stroke, and Cardiovascular Disease in Relatives (Affected and Unaffected) 

Silberberg128

lia 

tion study 

coronary event 

Controls (n=248) 

population controls 

from the same 

ified FH 

eference Standard: 

r 1DRs 

5] 

83] 

0) 

ontrols: 

99) 

ll heart 

DRs 

0] 

.71-0.87) 

76] 

HD: [0.80] 

ll heart 

DRs 

.59] (0.49-

[0.70] (0.58-0.80) 

Controls: 

.65-

ll heart disease: 

) 

eported for 2DRs 

8] (0.61-

.75) 

: 

-0.86) 

 (0.60-

.71) 

e: 

.74] (0.67-0.80) 

1998 

Austra

Cases: 

patients (n=432) 

with CHD enrolled

in popula

that registered all

suspected of 

region 

Index Test: Mod

questionnaire from 

literature 

R

Death certificates 

CJD reported 

fo

Cases: 

CHD: [0.8

(0.74-0.92) 

All heart 

disease: [0.

(0.75-0.9

C

CHD: [0.95] 

(0.84-0.

A

disease: [0.90] 

(0.80-0.96) 

Reported for 

2

Cases: 

CHD: [0.8

(0

All heart 

disease: [0.

(0.69-0.82) 

Controls: 

C

(0.72-0.86) 

A

disease: [0.76] 

(0.70-0.81) 

CHD reported for 

1

Cases: 

CHD: [0

0.69) 

All heart disease: 

CHD: [0.74] (0

0.82) 

A

[0.83] (0.73-0.90

R

Cases: 

CHD: [0.6

0

All heart disease

[0.80] (0.72

Controls: 

CHD: [0.65]

0

All heart diseas

[0

Bensen124

1999 

U.S. 

Sample from the 

NHLBI Family 

Heart Study 

(n=3020) selected 

randomly and nonrandomly 

(oversampled with 

CHD). Some of the 

probands had 

CHD, diabetes, 

hypertension, and 

asthma 

Index Test: 

Mailed questionnaire 

including personal history 

and FH (1DR and 

spouses) 

Reference Standard: 

Same questionnaire as 

probands 

Proband vs 

Parent 

0.85 (p=0.023) 

κ=0.76 

Proband vs 

Sibling 

0.81 (p=0.015) 

κ=0.80 

Proband vs Parent 

0.93 (p=0.010) 

κ=0.76 

Proband vs Sibling 

0.98 (p=0.002) 

κ=0.80 

CHD CHD 

99 
Table 11. Accuracy of self-reporting of FH for relatives with other diseases (continued) 

Study Population/ 

Design/ Sample 

Size

Index Test (FH) 

Reference Standard Accuracy 

 Sensitivity(95

%) 

a/a+c; value[ ]

Specificity(95%) 

d/ b+d; value [ ]

Hypertension, Stroke, and Cardiovascular Disease in Relatives (Affected and Unaffected) 

Klungel125

1999 

The 

Netherlands 

h 

sed 

ation 

ascular 

iseases with question on 

eference Standard: 

edial records 

rda

I in father: [0.07] (0.04-0.10) 

ther: [0.0 (0.02-0.07) 

Probands wit

hypertension 

(n=899) subjects 

from a crosssectional 

population-ba

study (n=36,000)

Index Test: 

Self reported inform

on cardiov

d

FH 

R

M

Overall conco nce [κ] (95% CI): 

M

MI in mo 5]

100 
Question 3. What is the Direct Evidence That Routinely 

Getting a Family History Will Improve Health Outcomes for 

the Patient and/or Family? 

General Approach 

s ecte r

tion of F on-s e

ia outc g 

intention, uptake of and adherence to screening tests and procedures, preventative 

health behavio oph ent and surgery.167

Our focus at ual

W

c

e el d studies that identif

H in a typical, n

te health related 

r,129,130,162 and pr

 was on the system

ied the impact on health

elected primary care/gen

omes identified from stud

elated outcomes of systematic 

colle

Appropr

158

ral population. 

ies included patients’ screenin

136,158-166

ylactic preventive treatm

ic collection of individ FH information, and communication 

of personal risk of one or more of f interest, in populations considered 

representative of primary care populations. In line with the decision to identify the highest level 

of evidence, only published intervention studies (RCTs, controlled trials, and uncontrolled 

before-after studies), where the intervention was the systematic collection of FH and this was 

compared to current or control clinical practice, were included for this question. Webtable 30 

identifies those studies excluded, primarily because the design was not the specified intervention 

study design. 

Studies Reviewed 

Only two studies were identified for data abstraction after full text review of 34 studies.129,130

Both were uncontrolled before-after studies and focused on breast cancer risk assessment, 

including FH collection, as the target intervention. 

The employer study focused on telephone based risk assessment (including systematic FH 

collections) in female patients at their place of work. In the study,129 all 8,900 women employees 

were sent electronic mail and there was a poster campaign about the breast cancer telephone risk 

assessment service. Five percent (444) took up the service and 343 completed the telephone 

survey, with 189 agreeing to divulge their names and addresses, enabling followup. These 189 

subjects were sent a followup postal questionnaire at 8 months, achieving a response rate of 72 

percent (136). The baseline telephone survey and followup postal survey enquired about the 

outcome measure of mammography, as well as reporting clinical breast exam (CBE) and breast 

self exam (BSE). 

In the other study130 participants were recruited, on a walk-in basis, through six community 

pharmacies and two health promotion events for women aged 18 years or older. Prior to 

intervention, respondents completed a baseline survey (as indicated in Table 12). The risk factor 

data (including FH) was input into a breast cancer risk assessment tool. This tool used the Gail 

model for risk calculation, which requires information on the number of 1DRs with breast 

cancer. This was followed by a pharmacist consultation to discuss individual breast cancer risk, 

supplemented by written information. All women, irrespective of risk status, were encouraged by 

the pharmacist to follow American Cancer Society (ACS) guidelines for BSE, CBE and 

mammography. As with the employer study, the baseline and followup surveys enquired about 

adherence to mammography, (together with adherence to CBE and BSE). 

 

the conditions o

101 
Out

factors (including FH) wom e, moderately increased, 

r markedly increased breast cancer risk. All women were advised to perform CBE and regular 

en had a similar age range to the general U.S. population but 

a hi men 

R diagnosed with 

bre nd 

as 

mography 

scre

nt in BSE 

isk of breast cancer in 5 years), which appears higher than would be expected for 

 unselected female population in this age group. In addition, the high baseline rates of 

ompared with published figures for the general population may 

ited external validity. 

lative 

1) to 71 percent (15/21), although this did 

not

se 

comes 

The study findings are summarized in Table 12. In the employer study, based on 12 risk 

en were classified as being at low to averag

o

BSE and mammography. 

The original cohort of 343 wom

gher proportion reported recent mammography. Further, a high proportion of the 343 wo

initially recruited had a FH of breast cancer with 10 percent (34) having a 1D

ast cancer before the age of 50. Of the 136 women who completed both telephone survey a

followup postal survey, 52 percent (70) reported changing breast screening behavior. There w

a statistically significant improvement in the two risk reducing behaviors: Mam

ening improved from 76 to 93 percent but the matched sample was small (29) and the change 

in screening did not reach statistical significance (p=0.057). There was also improveme

(34 to 62 percent; P<0.001) and CBE (82 to 92 percent: p<0.0137). There was no differentiation 

of the improvement in breast screening habits between the different risk strata. 

The community pharmacy study drew participants from women attending pharmacies and 

heart health events, and no specific data were presented regarding representativeness. Their 

analyses indicate that 21 of 140 (15 percent) participants were assigned to the high risk category 

(≥1.7 percent r

an

mammography and CBE c

indicate that this study has lim

There was limited improvement in adherence to mammography in all women (p=0.796) and 

each age group (40-49; >= 50 years old). Further, in high breast cancer risk women (with re

risk >=1.7) the adherence fell from 81 percent (17/2

 reach statistical significance (p<0.317). Results were also presented for other process 

measures: the proportion of women performing BSE increased from 31 to 56 percent, while 

mean BSE performed over 6 months increased from 2.79 to 4.1. Both metrics identified 

statistically significant changes (p<0.001). Changes in CBE were less dramatic with an increa

from 86 to 91 percent (p<0.09). However, in younger women (aged 40-49) the change was 

slightly more significant with improvement in CBE from 81 to 99 percent (p<0.025). 

102 
Table 12. Descrip

e patient and/or

tion of studies with evidence that routinely getting a FH will improve health outcomes for 

 family 

Author 

th

Year 

Design 

Setting 

Target 

Behavior 

Population

n 

Followup 

FH Collection 

Component of 

Intervention 

Who 

Delivered 

Intervention 

Outcome 

Measures Findings 

Kadison129

1998

Screening Female Telephone- Automated Compl with Proportions

Before-after 

Two large 

employers, 

Boston, MA, 

U.S. 

mammo 

BSE 

Clinical 

breast 

exam 

employees 

invited by 

electronic 

mail 

n=343 

recruited 

n=136 

followup 

at 8 months

administered 

survey for 12 

Risk factors. 

1. Number of 

1DRs with 

breast cancer 

(inc. age of 

diagnosis); 

Relatives with 

bilateral breast 

cancer. 

2. Other risk 

telephone 

based Breast 

Cancer Risk 

Assessment 

System: real 

time risk 

information 

and option of 

paper copy of 

risk 

assessment 

and advice 

monthly 

BSE, CBE 

by a 

healthcare 

practitioner 

and 

mammo 

comply with 

screening 

BSE 

Pre: 40/119

Post: 74/119 

p<0.001 

CBE 

Pre: 98/119 

Post: 

110/119 

p<0.0137 

Mammo 

factors: 

age at 

menarche, 

pregnancy 

history, age 

and weight at 

menopause; 

history of 

ovarian/uterin

Pre: 22/29

Post: 27/2

(in 6 mo

following 

assessment)

p<0.0572 

e 

9 

nths 

cancer; chest 

radiotherapy 

Abbreviations: 1DR=first degree relative; ACS=American Cancer Society; BSE=breast self exam; CBE=clinical breast exam; 

Compl=Compliance; FH=family; Mammo=Mammography; n=number of subjects; y=years 

103 
Table 12. Description of studies with evidence that routinely getting a FH will improve health outcomes for 

the patient and/or family (continued) 

Author 

Year 

Design 

Setting

Target 

Behavior

Population

n 

 Followup

FH Collection 

Component of 

Intervention

Who 

Delivered 

Intervention

Outcome 

Measures Findings

Giles130

 2001 

Before-after 

ealth 

screening 

event, 

Richmond, 

VA, 

U.S. 

months 

er 

ber of 

f 

SE, 

y 

E, ines 

/137 

8)) 

7 

)) 

)) 

1 

(87-96)) 

p<0.09 

Mammo 

≥50y 

Pre: 33/44 

Post: 31/44 

(70 (57-84)) 

p<0.48 

40-49y 

Pre: 18/32 

(56 (39-73)) 

Post: 21/32 

(66 (49-82)) 

p<0.257 

Community 

pharmacies 

and h

Screening 

mammo 

BSE 

Clinical 

breast 

exam 

Women 

≥18y 

invited by a

walkup 

basis

 

n=188 

recruited 

n=140 

followup 

at 6 

Intervieweradministered 

survey: 

1. Number of 

1DRs with 

breast canc

2. Other risk 

factors: 

age at 

menarche, 

age at first live 

birth, num

breast biopsies 

3. Other:

history o

practicing B

formal 

instruction in 

BSE, 

confidence in 

performing

BSE, 

history of 

mammograph

Community 

Pharmacist

Adherence 

with ACS

guidelines 

for BS

CBE, and 

mammo 

Proportions 

following 

ACS 

guidel

(selfreporting) 

(% (95% 

CI*) 

BSE 

Pre: 42

(31 (23-3

Post: 77/13

(56 (48-64

p<0.001 

CBE 

Pre: 121/140 

(86 (81-92

Post: 

128/140 (9

(75 (62-88)) 

Quality Assessment of Studies 

In the before and after employer study there appears to be selection bias, with recruited 

participants being younger and having higher breast cancer risk than the U.S. general population, 

and with higher proportions reporting recent mammography. If it is assumed that the 4 percent 

(343) of invited patients who participated and completed the baseline survey were more health 

conscious, then there is also a potential for recall bias. Over the 8 months of the study response 

rate fell from 77 percent of the 444 participating women completing the baseline telephone 

survey, to 31 percent (136) at followup. The telephone-based breast risk assessment intervention 

took place at the same time as a Breast Cancer Awareness Month at one employer, making it 

difficult to determine whether the improvement in breast screening behavior was a direct 

consequence of the telephone-based service. 

104 
The community pharmacy study was described as a ‘randomized, paired, pre-post study’, 

which is misleading. In our assessment, it was an uncontrolled pre-post study in which beforeafter outcomes f idu ts as p ata. N group was 

used and therefore no random n h r stu 

given that no assessment co e o e o tors, or placebo or 

rne ef tu ted ampl lati u

baseline ce ra e us, e u gh 

0-80 percent BE and p esting a possible c t).

onclusio

e e for a Q3 ed to two studies. This was primarily due to 

 on study design o, clearly defining the population as representative

cluded the numerou in a g. In both studies, familial bre

t considered in ut ifactorial risk assessment too

ble to disentangle the f the ent from the other risk facto

s, the interventions did not really r he routine, personal interaction, wh t 

ary care professional and an individual patient. In the employer

assessment was offered to all women em s of two large U.S. organizations. It m

expected that such a recruitment procedu representative of the general population, 

however, the recruited patients were more representative of a high risk population (in

high familial risk). Similarly, the recruit re different from the general po in 

other ways: baseline mammography screening le atched data indicated 

population already had a high BSE rate. The external validity of the results was also affected by 

non-response to followup survey and, as by authors, the study was und

for some of the outcome measures. The low participation rate (5 percent) is a weakne

study, but it probably represents a realistic situation when an open invitation for risk 

is offered to the general uninformed population. Both uptake of this service and follo

screening would be improved if recommended by the woman’s usual physician. In th

community pharmacy study, the subjects were recruited through a local screening campaign, and 

no data was available on the representativeness of the recruited women. Like the employer study, 

the proportion of women at high breast cancer risk and the baseline screening behavio

higher than expected for an unselected U.S. population. As well as concerns about the external 

alidity of both studies, they were only able to assess process measures (mammography 

screening being the only outcome with evidence of 

ited improvement in mammography 

scre

or indiv al participan were analyzed

 was possible. T

f the influenc

aired d

e potential fo

f external fac

o control 

 a atio bias in this 

uld be mad

lloc dy is high,

Hawtho fects. The s

adheren

dy indica

tes may hav

 mammogra

an a priori s

 been erroneo

e size calcu

 as they wer

on; their ass

nusually hi

eiling effec

mptions 

about at around

7 for C hy (also sugg

C n 

The evid nce bas

restrictions

care ex

risk was no

ddressing is limit

 but als

s studies 

 of primary 

 specialist settin ast cancer 

as part of a mult

ssessm

isolation b

impact o

l. It was not 

possi h 

tudie

 FH risk a rs. In bot

s igh

occur between a prim

esemble t

ployee

re would be 

ed patients we

vels and the m

ich m

 study, risk 

ight be 

cluding 

pulation

the 

 acknowledged erpowered 

ss of the 

assessment 

wup 

e 

r was 

v

screening; BSE; CBE), with mammography 

improved health outcomes. In both studies, there was lim

ening however, the sample sizes were small. Further, in the community pharmacy study 

subanalyses suggested those identified at high breast cancer risk adhered less to mammography, 

however this change was not statistically significant, with high baseline screening rates. 

105 
Question 4. What is the Direct Evidence That Routinely 

Getting a Family History Will Result in Adverse Outcomes fo

the Patient and/or Family? 

General Approach 

We reviewed published studies, which assessed negative impacts of systematically

r 

 collecting 

FH information and providing patients with familial risk information for any medical condition. 

The focus was on systematic collection of individual FH information, and communication of 

personal risk of one or more of the conditions of interest, in populations considered 

rep

133

e 

ety, 

f-

 the 

consultation. 

The two other studies131,132 were both uncontrolled before-after studies with different 

interventions. One131 evaluated the psychological impact of collecting cancer FH information 

through a postal questionnaire distributed to all patients in the 35 to 65 age group, followed by 

individualized assessment of their genetic risk of CRC and breast cancer (where appropriate). 

General anxiety and cancer worry were assessed at baseline and 4 to 6 weeks after risk 

information feedback using the STAI and a multidimensional cancer worry scale, respectively. 

resentative of primary care populations. 

The adverse psychological outcomes of interest identified at full text review included 

perceived risk,158,160,162,166,168,169 and perceived vulnerability and worry.131-133,158,162,168 

In line with our decision to identify the highest level of evidence, only published intervention 

studies (RCTs, controlled trials, and before-after studies), where intervention was the systematic

collection of FH and this was compared to current or control clinical practice, were included for

this question. Webtable 30 identifies those studies excluded, primarily because they were not the 

required intervention study design. 

Studies Reviewed 

After reviewing 38 studies at full text, only three studies met all eligibility criteria.131-

These studies recruited patients from single British primary care offices with the number of 

respondents recruited varying from 100 to 666 and response rates of 19, 29, and 64 percent. 

Descriptions of each study are given in Table 13. A sample size calculation was provided in on

of the studies.133 The proportion of recruited patients completing survey items at all time points 

was 91, 89, and 76 percent respectively.131-133

One paper133 described a randomized controlled trial (RCT) comparing general anxi

health status and specific FH measures between control patients receiving a general health check 

and intervention patients who completed a FH risk assessment with the health check. Outcomes 

were measured using the self-administered short form (six items) Spielberger State-Trait 

Inventory (STAI) and the five item Perception of Health Questionnaire at baseline, 1 week, 2 

weeks and 3 months after first visit. The 12-item FH concerns measure (adopted from sel

administered Psychological Consequences Questionnaire) was also completed at 2 weeks and 3 

months. The health check comprised two visits: baseline to record standard health check 

variables and, in the intervention arm, the self-completed FH questionnaire. Two weeks later

results of the health check and FH questionnaire were reported back to the patient, including 

recommended action. The 2 week outcome survey was completed immediately after this 

106 
T g 

immediately before and afte with the short form 

STAI. 

Outcomes 

six 

I score at 

d falling back to 37.1 at 2 weeks; in the control 

gro

ion group 

at 1

ne and 1 week post-visit to questions about risk to future 

health, compared to the control group (26 vs. 7 percent; p=0.025). There was no significant 

 groups regarding FH concerns at 2 weeks and 3 months. 

Lower risk’ (those at no more than 

slig k 

e 

erception of their own risk (p<0.01). 

 led 

y and 

oup 

 with 

d for 

ning. In the clinic, a three generation FH was recorded using a standard proforma 

and

a 

r 12 

he other study132 assessed the impact of offering a familial risk assessment and counselin

clinic to identify genetic and preconceptual issues in patients of child-bearing age (20 to 34). As 

well as identifying the uptake and acceptability of the clinic, general anxiety was assessed 

r the clinic appointment and 12 weeks later

 In the first study133 156 patients were randomly assigned to control and intervention 

groups, with 100 patients attending doctor’s office for routine physical examination. Seventycompleted outcome surveys at all 4 time points. In the intervention group, mean STA

baseline was 36.7, rising to 39.4 at 1 week an

up STAI mean score was similar at baseline but fell at 1 and 2 weeks (to 32.5 and 33.0 

respectively). This corresponded to a significantly higher anxiety score for the intervent

 and 2 weeks post clinic visit (p=0.014). The mean scores for the intervention and control 

groups at 3 months were not significantly different (34.2 and 34.8 respectively). When 

comparing perception of health scores at different time points, the only significant change 

between the groups was that a larger proportion of the FH intervention group gave a more 

pessimistic response between baseli

difference between the two

he second study131 T analyzed participants in two groups. 

htly elevated risk) participants, for whom no followup was necessary, were given feedbac

by letter only. The outcomes for this group are summarized in Table 14. The STAI at baselin

and 4-6 week followup were similar (35.8 and 35.1 respectively), corresponding to no 

statistically significant difference observed in anxiety. Similarly, most other cancer worry 

measures identified no statistically significant change following the intervention, with the 

exception of a small reduction in participants’ p

Of the remaining participants, most were interviewed to clarify details of their FH, which

to further designation into ‘higher risk’ and ‘false positive’ groups, the latter comprising patients 

deemed not actually to be at high risk after further enquiry. For both ‘higher risk’ and ‘false 

positive’ groups, no difference between baseline and followup responses to general anxiet

cancer worries scales was observed. However, both of these groups showed higher baseline 

cancer risk perception scores compared to the lower risk group (p<0.001 for ‘higher risk’ gr

and p=0.003 for ‘false positive’ group). 

In the third study132 124 patients attended the primary care office-based genetic clinic,

121 completing the pre- and post-clinic STAI and 91 returning the 12th week. Eighty-nine 

patients completed the survey at all 3 time points. Fifty-four percent (67/124) of patients 

attended clinic due to concerns about possible familial illness, and 35 percent (43) attende

pregnancy plan

 risk was assessed by primary care providers (family doctor and health visitor) against 

regional guidelines, literature, and standard texts. Forty percent (50) of patients had a FH with 

genetic component, however only 7 percent (9) required specialist input. Based on all the 

completed surveys at each time point, the mean STAI score at baseline was 34.8, falling 

significantly to 30.1 (p<0.001) right after the consultation, returning to initial levels afte

weeks (33.0). As commented by the authors, a significant proportion of the genetic counseling 

107 
108 

inv

s for 

uthor 

Design 

se Population 

n 

Time 

Points 

for 

Analysis 

Duration / 

Nature of 

Interventio

n 

Who 

delivered 

Interventio

n 

Method of 

FH 

Collection 

Other 

Intervention 

olved reassuring patients that they were at “low” familial risk. In the study publication, there 

was no differentiation of anxiety scores between the different risk strata. 

Table 13. Description of studies with evidence that routinely getting a FH will result in adverse outcome

the patient and/or family 

A

Year 

Setting Disea

Leggatt1

31

2000 

U.K. 

Before - 

After 

ucon 

study 

Colorectal/

colon/rectal 

Breast 

cancer 

Unselected 

patients 

aged 35 to 

65 years 

registered 

at one 

general 

practice 

Recruited= 

666 (29% 

response) 

Completed

=604 

Baseline 

1-1.5 

months 

N/A 

Postal FH 

question 

Lower risk 

group: 

letter from 

family 

doctor 

Potential 

increased 

risk groups: 

family 

doctor 

and/or 

Oncologist/

geneticist 

Postal 

cancer FH 

question 

Participants

provided wi

risk 

informa

th 

tion 

Qureshi1

33

Generic Random Baseline Two FH In-office 

2001 

U.K. 

RCT 

covered all 

conditions 

identified 

by 

respondent 

selection of 

patients 

aged 18-60 

registered 

at one 

general 

practice for 

at least 2 

1 week 

2 weeks 

3 months 

consults, 

two weeks 

apart 

(completing 

FH 

question 

and health 

check in 1st

screening 

question 

intervention 

only: 

self-admin, 

results 

reviewed 

by a clinical 

self-admin 

FH 

question 

with prompt 

sheet of 

relevant 

conditions 

years, and 

who had 

not 

received a 

health 

check in 

that time 

Recruited= 

consult) geneticist 

Health 

Check 

(control + 

intervention

): 

Researcher 

100 

(64% 

response) 

Completed

=76 

results 

reviewed 

by a GP 

Abbreviations: FH=family history; FHQ=family history questionnaire; GP=general practitioner; Immed=Immediate; N/A=not 

applicable; question=questionnaire; RCT=randomized controlled trial; ucon study=uncontrolled study
Table 13. Description of studies with evidence that routinely getting a FH will result in adverse outcomes for 

the patient and/or family (continued) 

Duration / Author 

n

Time 

for 

sis

Who 

Interventio Collection Intervention

Year 

Setting Disease Population Points Nature of 

Interventio delivered Method of 

FH Other 

Design Analy n n

Rose132

ll 

conditions 

tients 

aged 20-34 sult 

g a 3 

ration 

question) 

itor. 

in 

ants 

lessons on 

formation 

garding 

familial risk 

1999 

U.K. 

Before 

and 

After 

uncon

study 

Generic 

covered a

identified 

by 

respondent 

Unselected 

pa

years 

registered 

at one 

general 

practice, 

excluding 

pregnant

women 

Recruited= 

124 (18.9% 

response) 

Completed

=91 

Baseline

Immed 

postconsult 

12 weeks

30 minute 

genetic 

con

(takin

gene

FH and 

completion 

of 

GP and 

health 

vis

the latter 

had 

previously 

worked as 

a clinical 

nurse 

specialist 

genetics 

Recorded 

on a pro 

forma 

during 

clinic appt 

Particip

provided with 

pregnancy 

planning, 

lifestyle 

factors, and

general 

in

re

109 
Table 14. Findings from studies with evidence that routinely getting a FH will result in adverse outcomes for 

the patient and/or family 

Author Measur

Descr

u

a

e(s) of S in Find

An

iption 

bjects 

lyzed 

Subjects Main Find gs Other ings 

L 131 eggett

2000 

Anxiety 

er w

ve

sk o

developin

-freq. of c

related 

thoughts 

- effect 

performan

daily task

- effect on

mood 

“Lowe

Group

n=568 No an

ch e 

ine an

p for

asur

o 

significant 

ge

eline

p

k gro

U.K. Canc

scales 

- percei

own ri

cancer 

orry 

d 

f 

g 

ancer 

ce 

s 

r risk” signific

ang

t Also n

between 

basel

followu

d 

es 

chan

bas

followu

both me ris

 between 

 and 

 in other 

ups 

Qureshi133

001 

U.K. 

Spielberg 

State-Trait 

Anxiety 

Inventory 

(STAI) – short 

form 

Perception of 

Health 

Psychological 

Consequences 

Questionnaire 

(FH Concern) 

All enrolled 

patients aged 

18-60 years in 

single primary 

care office 

completing 

questionnaires 

at all 4 time 

points. 

Complete 

data at all 4 

time points 

Control: 

n=42 

Intervention: 

n=34 

State Anxiety 

score (at 

weeks 1 and 2) 

higher in the 

intervention 

group than 

control 

(p=0.014), but 

did not persist 

(no significant 

difference at 3 

months) 

Perception of 

health measure: 

significant result 

at week 1, the 

intervention 

group having a 

more pessimistic 

response to the 

question eliciting 

pts concerns 

about future 

health (p=0.025) 

FH concern 

measure: no 

significant 

difference at 2 

weeks or 3 

months 

2

Rose132

1999 

U.K. 

Spielberg 

State-Trait 

Anxiety 

Inventory 

(STAI) – short 

form 

All enrolled 

patients aged 

20-34 years in 

single primary 

care office 

Complete 

baseline 

STAI: 121 

+12 weeks: 

n=91 

State Anxiety 

score fell 

immediately 

after the 

consultation 

(p<0.001) and 

rose to preclinic levels at 

12 weeks 

Main lessons 

learnt by pts 

during 

consultation 

related to 

pregnancy 

planning and lifestyle advice, as 

well as genetics 

related topics 

Abbreviations: FH=family history; Freq=frequency; n=number of subjects; p=probability; pts=patients 

110 
Quality Assessment of Studies 

Two of the e es w lled er s il

was a RCT.133 All took place in s

dard ality asse klist ployed ha

mized tr 133 he ed Jadad scores were 5 o r this s

ndomization procedure was described in the paper, the al edu

Similarly, crit ipant inclusion were given, but no e eria

A sample size was reported for the primary outcom se 

events of the intervention was not scored but the objective of the study was to identify such 

factors. Further, the study did not report measures to achieve blinding. 

No formal ent checklists were employed on the two uncontrolled before-after 

studies.131,132 Neither study compared respondents and non-respondents to the familial risk 

assessment invitation. However, both did attempt to elicit profiles of non-responders in other 

ways. In one study, respondents were compared to the overall practice population, identifying 

that more older subjects took up the offer.131 The other study noted 81 percent of invited subjects 

did not respond, and a fifth (n=144) of these non-responders were sent a postal survey. One 

hundred and ten subjects replied with nearly 50 percent stating their reason for non-attendance 

was inconvenient time or lack of time, while another 40 percent were not motivated or 

 as releva ethe orte cal

clusio

The evidence base for addressing Q4 is limi three stu mize

trial133 and two uncontrolled be es 31,132 s ct

collection and am rma el olo

the medium term ho p the FH Le

identified the tween breast cancer familial risk s o t. 

There was no deleterious psychological effect in any of the risk while in

were at or just above average risk, the FH risk assessment may have led to appropriate reductions 

in perceived r

The most common psychological measure in all three studies was the short f AI. 

However, the clinical significance of the score remains unclear. The baseline sc H 

intervention arms did vary between the three studies from 34.8132 to 36.7.133 The three studies 

ed differ rm im en stu s a e in 

y score seco e th as n ther 

1 ies did te sco low risk 

groups. In this as in the ty and ca n bo ups at 

4 and 6 weeks after cancer FH assessment. However, the findin se f 

these psychological measures in the groups who went on to ha ssm o 

explain and may reflect the effects of having a positive FH in i n 

information collected and assessed. Of the three studies only Leggatt et al.,131

 u

ific measure was 

dopted from a validated instrument (PCQ) but it did not demonstrate any significant impact of 

e FH collection intervention.133

ligible studi ere uncontro before-aft tudies,131,132 wh e the third study 

ingle primary care offices. 

A stan ized qu ssment chec was em on the study t

ut of 8 fo

location proc

xclusion crit

e measure. Ident

t used a 

tudy. Although 

re was not clear. 

 were described. 

ifying adver

rando

the ra

ial design. T modifi

eria for partic

 calculation

 quality assessm

considered sessment ir

n 

nt to them. N

fore after studi

ilial risk info

r study rep d sample size 

dies, a rando

uggest that stru

eterious psych

 intervention. 

tatus and psych

 groups,

culations. 

d controlled 

ured FH 

gical effects in 

ggatt further 

logical impac

 women who 

Con

ted to 

.

1 These

tion had no d

took u

 feedback of f

 (6-12 weeks) on patients w

relationship be

isk. 

orm of the ST

ores in the F

show ent short te

while in the

31 the stud

 study, there w

pacts of interv

nd,132 the score f

 not differentia

 no change 

tion, in one

ell and in th

dy,133 there wa

ird131 there w

res between

ncer worry i

g of higher ba

ve further asse

tself, rather tha

 short tem ris

o change. O

er and higher 

th risk gro

line levels o

ent is difficult t

having FH 

sed a validated 

anxie

than Leggatt,

t

 the anxiety 

 anxie

context-specific measure (cancer worry scale). In another study a context-spec

a

th

111 
Question 5. What are the Factors That Encourage or 

r 

een 

w, 

he 

another two studies the population was derived from patients being screened in the general 

ere cross-sectional.135,136,138,139 The remaining two studies were a direct 

obs 34

en were included). Of 2,715 women in the sampling 

Discourage Obtaining and Using a Family History? 

General Approach 

Initially there was limited clarity on the breadth and depth of this research question. After 

extensive review of the diverse literature in this area and a series of discussions with the 

technical expert panel, we focused the reviewed publications on studies that clearly identified the

association between factors that facilitate or inhibit the process of collecting, discussing, and/o

using FH. Within the group of studies collecting FH, studies evaluating the association betw

self reported FH and other factors were separately collated. The process of FH collection, 

discussion and use can be influenced by attributes of the patient, the health care professional, and 

the setting in which the FH is identified. In line with the overall scope and purpose of the revie

the patients were from populations representative of a primary care setting, while the 

practitioners would have been primary care providers (as discussed in Chapter 2). 

Studies Reviewed 

Of the six studies identified, four were undertaken in primary care offices134-137 and in t

population.138,139 

Four studies w

ervational study137 and a prospective cohort study with a baseline cross-sectional survey.1

Factors associated with FH collection or discussion were the primary outcomes of interest of

three studies.136,137,139 This relevant data from the other three studies were retrieved from 

subanalyses presented in these publications.134,135,138 Two studies only recruited female 

patients.136,138

The cross-sectional surveys recruited between 500 and 149,332 subjects. The direct 

observational study followed 4454 patient visits and the cohort study surveyed 163 patients. 

In Murff et al.,136 patients with at least one visit to the primary care provider over the 

previous year were randomly selected from 11 primary care practice sites in the Greater Boston 

area. As well as medical record review, the consenting patients completed a telephone survey. 

This survey identified sociodemographic factors and satisfaction with health care. Only 2,858 

women were included in the sampling frame for the study. The average age of the women was 

47.6. The response rate was 62 percent (1,803) with responders more likely to have had a 

mammogram performed in the last 5 years. Fletcher et al.,135 also randomly mailed 

questionnaires to 6,807 of 31,959 patients aged 35 to 55 years old in a single large multispecialty 

group practice about FH of colorectal cancer and screening experience. Twenty-eight per cent 

(1,854) of this sample completed the postal survey, with 19 percent (355) of these respondents 

reporting a FH of colorectal cancer. 

In Karliner et al.,138 the sample was derived from 14,490 women in the San Francisco area 

who had had a mammographic screening in the previous 2 years and completed a baseline 

questionnaire at the time of screening. The questionnaire identified women’s familial risk using 

the Gail model. In the sampling frame, women were randomly sampled according to risk status 

(although all higher risk minority wom

112 
frame, 

collecte sk 

and cre f the 

74 years. The publication reports on the 149,332 subjects who 

f the baseline survey in a national multi-cancer screening trial. The 

expected prevalence rates of various cancer types were compared to observed levels for different 

rela

l 

oston. 

ong 1,098 subjects contacted by mail, 17 percent (189) consented to participate in the study, 

pleting a postal survey that incorporated a structured format to obtain 

FH information. As well as the survey, consenting subjects agreed to have their electronic 

med he 

Ou

tor, 

,170 The 

are summarized in Table 15. 

risk 

ver

r 

s identified 

etter identified by systematic FH surveys. Compared to 

EH

ily 

ween 

63 percent (1,700) completed a followup telephone survey. The telephone survey 

d information on sociodemographic data, as well as, information on breast cancer ri

ening behavior. Pinsky et al.,139 s also sampled from a large cross-sectional survey o

general population aged 55 to 

completed the FH section o

tives and gender of respondents. Further, the relationship with various socio-demographic 

factors was also identified. 

In Acheson et al.,137 researchers directly observed consultations of 138 community family 

physicians over 2 separate days (4 months apart), with a standardized consultation encounter too

(modified Davis Observation Code). The study was restricted to family physicians practicing in 

North East Ohio, although the profile of the physicians was representative of physicians 

throughout the U.S. The observation was supplemented by a review of medical records, 

physician surveys, and field notes. Full details of the FH information was only extracted from 

medical records in the latter half of the study. 

The study by Volk et al.,134 also recruited from a single primary care office in B

Am

with 15 percent (163) com

ical records scrutinized for FH information and compared to the information collected on t

survey. 

 

tcomes 

In the six studies, the FH outcome was predominantly a dichotomized variable. The 

outcomes of interest were: FH documented in medical records;134,136 FH discussed by doc

either confirmed by direct observation137 or patient survey;135,138 and self reported FH.139

study findings 

FH recorded in medical records. Murff et al.,136 noted a comprehensive cancer FH 

assessment was more likely to be documented in white patients’ medical records (84 percent 

sus 67 percent in non whites), and in patients where English was the first language (94

percent English versus 85 percent), both with p<0.001. When dichotomized by age (less than 40 

or 40 years and older) the ethnic difference remained. In the under 40 group, FH of breast cance

interviews occurred in 30 percent of white women, compared to 15 percent of African 

Americans and 11 percent of Hispanics (p<0.001). No information was presented on provider 

factors (practitioner and setting). 

Volk et al.,136 identified a different factor in FH collection, the type of condition

in electronic health records (EHR) in U.S. primary care practice. Forty-seven percent of EHRs 

had a FH recorded (93/189). Compared to the postal FH survey, the EHR collected FH of 

diabetes, breast cancer, CHD, but 90 percent of positive family histories of glaucoma, 

osteoporosis, and colon cancer were b

Rs, the survey also identified further FH details on glaucoma, osteoporosis, and diabetes 

leading to alteration in their familial risk status (94.7, 95.0, and 73.8 percent of positive fam

histories, respectively, changed risk status). 

FH discussed in consultation. Acheson137 identified the FH information discussed in 

consultations. FH was discussed in 24 percent of consultations. This study differentiated bet

113 
factors that influenced discussion of FH between newly registered patients at the doctors’

and established patients. Recently appointed physicians (as indicated by being in practice for 

fewer years) were more likely to discuss FH with established patients (p=0.02). In addition, 25 

percent of residency trained practitioners discussed FH with established patients compared to 

percent of non-residency trained practitioners (p=0.06). There was no association with 

practitioners who offered prenatal care. 

In the case of patient factors: the age, gender, health and marital status were explored for 

established and new patients

 office 

70 

. The only significant association was that older established patients 

wer

ts, 

le 

 being addressed in the consultation in 

bot

y or 

n with younger women (p<0.0001), women who had had a routine physical 

exa (p=0.0001), and women concerned about breast cancer (p=0.006). In 

5

 women younger than 50 were less likely to be asked about their FH of colon or 

rectal cancer with 39.1 percent asked [95 percent CI: 36.1-42.0%] compared to 72.2 percent 

ask

t (11.8 percent), lung (10.1 percent), colorectal (9.4 

per ) 

d 

r 

rveyed 

e less likely to discuss FH than younger established patients (age 15 to 44, 24.8 percent; 65

years or over, 17.6 percent; p<0.001) Further, patients with Medicare insurance were less likely 

to be asked about FH. 

Family history was discussed in 61 percent of physical examinations with new patien

compared to 44 percent of such checks in established patients. During these checks, fema

patients were more likely to discuss FH. When FH was discussed this seemed to extend the 

consultation time and be associated with other problem

h new and established patients. 

Kartliner et al.,138 surveyed women who had attended mammography screening. The study 

explored multiple factors associated with clinicians discussing cancer FH. Jewish ancestry, 

education, language of interview, insurance status, previous cancer investigations, and worr

risk perception were not associated with clinicians discussing cancer FH. However there was an 

associatio

mination in the last year 

Fletcher et al.,13

ed in those 50 years and older [95 percent CI: 70.0-76.4%]. 

Factors associated with self-reporting FH. Pinsky et al.,139 noted in a cross-sectional 

survey that male respondents reported less FH of cancer than female respondents. The most 

common family histories reported were breas

cent), and prostate cancer (7.3 percent), with lymphoma (0.6 percent), vaginal (0.1 percent

and testicular cancer (0.4 percent) being less commonly reported. Further, it appeared liver an

bone cancers were over-reported while lymphoma, melanoma, bladder cancer, and testicula

cancer were under-reported. Minority groups (Black, Asian, Hispanic) reported lower rates of 

FH compared to the non-Hispanic white group (p<0.01). Respondents with less than 8 years 

education also had lower rates but this group only represented about 1 percent of the su

population. 

 

114 
Table. 15 Factors associated with improved FH collection and utilization 

Factors Associated 

With Improved FH 

Collection in Medical 

Records 

Factors Associated 

With Medical 

Practitioner Discussing 

FH 

Factors Associated 

With Improved Selfreporting of FH 

Patient factors: White (compared to 139

rtery disease)

Not on state health 

Age: mixed picture, in 

age group for colorectal 

Women

Higher education status

cers: 

other ethnic groups)136

Certain medical 

conditions (diabetes, 

breast cancer, coronary 

a 134

insurance137

Patients who worry about 

breast cancer138

White non-Hispanics 

(compared to other ethnic 

groups)139

139

one study more likely to 

discuss in younger age 

group for all 

conditions,137 while in 

another study in older 

Certain common can

breast, lung, and 

colorectal139

cancer135

Practitioner factors: 

 

Practitioners in same 

practice for fewer years 

137

Resident-trained137

Setting: 

 

Routine physical 

examination in 

established patients,137

particularly women137,138

Abbreviations: FH=family history 

Quality Assessment of Studies 

In three of the identified studies the characteristics of respondents and non-respondents wer

identified with the respondents being older than non-respondents.134-136 One study examined 

other sociode

e 

mographic factors, noting respondents were more likely to be Caucasian,135 while 

 another survey, respondents had slightly more FH recorded in their medical charts and were 

more likely to have performed BSE and mammography screening.136 Of the five studies that 

used cross-sectional surveys, the response rate was 80 percent or over in three studies, two of 

which were based in primary care,134,136 and the other was a population-based survey.139 Of the 

remaining two studies, a telephone survey had a 63 percent response rate138 and a primary carebased postal survey achieved a 27 percent response.135 In most studies the nature of the FH 

discussed or reported was not clearly identified, often just reported as dichotomous variables. 

Only four of the six studies actually took place in primary care offices, and three of these were 

based in practices within the greater Boston area.135,136,138 Representativeness of these surveys is 

also limited by response bias and recall bias, for example Murff et al.,136 recruited older women 

and the responders were more likely to have had mammography screening. Collectively, these 

in

115 
116 

on is urged in applying this 

formation to clinica car

Conclusion 

 base het ited to ie exploring 

e association betwee d FH , cumentation and discussion. There 

i

care, for instance, pro to im . Howev certain 

patterns that maybe in si al examinations offer an appropriate screening 

“turnstile” to collect F m n appea han

appointed physicians were more enthusiastic ab re

FH collection and reporting in underserved gro hit

those with lower educational status,139 and thos ranc robably 

due to a combination of factors including poor difference in the nature of 

practitioners’ consultations with different grou

pragmatic resource issues: the potential of inco g the family history in electronic health 

ecords136 and extent to which discussing FH extended consultation time

ting family histories still n

issues limit the generalizability of the study findings; hence, cauti

in l situations in primary e. 

The evidence for addressing Q5 is 

 various factors an 

erogeneous and lim

reporting do

six stud s

th

was a paucity of evidence to help “operationali

n

ze” family history collect

prove collection

on and use in primary 

cedures and systems er, there are

formative. Routine phy

H. Further, wo e

c

red better informants t

out discussing FH. The

ups, specifically non-w

e on state health insu

recall by patients and

ps. Two studies also briefly considered other 

poratin 

 men did and recently 

 are also disparities in 

e ethic groups,136,139

e.137 This is p

r

r . The opportunity cost of 

systematically collec eeds to be explored. 
 

Chapter 4. Discussion 

Overview 

s 

r 

, 

s 

Q1. What are the Key Elements of a Family History in a 

Primary Care Setting for the Purposes of Risk Assessment 

for Common Diseases? 

As discussed in Chapter 1, for FH to be useful in chronic disease risk assessment, it is not 

enough for patients to report, and professionals elicit, FH information accurately: it is necessary 

to clarify which elements of FH are most useful for disease prediction.150 In specialist genetics 

settings, the gold standard, comprehensive, three generation pedigree forms the foundation for 

identifying specific potential disease inheritance patterns, such as autosomal recessive or Xlinked dominant.171,172 However, in a primary care context, the goal is usually to identify an 

individual’s overall level of familial risk, without necessarily seeking out specific patterns, 

though this is not precluded. Since, by definition, complex disorders are not likely to display an 

easily discernable, high penetrance pattern of inheritance, it is reasonable to take a simpler 

approach in which FH elements (e.g., type of relative, closeness of relationship, gender, age of 

onset, etc.) are combined and their predictive validity examined empirically. In principle, the FH 

definition which combines useful predictive power with least effort to obtain is likely to be the 

one best suited for routine application. Some insight into the ‘information value’ of different FH 

definitions might be useful in developing evidence-based, primary care-oriented FH tools,151

which could then be evaluated against appropriate control interventions for the effect of their use 

on health outcomes. 

 A large number of studies were identified that provided data relevant to this question, 

although they were mostly not designed for the analyses performed here. Only a very few reports 

were designed to examine different definitions of ‘positive FH’, and almost all assessed FH as a 

possible risk factor for disease in classical epidemiological approaches. Many of the cross-

 

This review was designed to inform a broad range of questions (Q) which ultimately addres

the clinical value of using family history (FH) in chronic disease risk assessment and prevention 

in primary care. 

The evidence derived from questions (Q) 1, 2, and 5 was designed to inform primary care 

providers of the most efficient elements of FH information, and approaches to collection, which

might be best suited to routine application, given the constraints that are faced such as limited 

time availability. This draws together the most informative components of an individual’s FH fo

future or current disease risk, the factors, which influence accuracy of reporting, and the factors

which stand in the way of, or promote, the actual collection of FH data. In addition, if primary 

care providers are to be persuaded that systematically collecting and interpreting FH is a 

beneficial activity, they need to be provided with the most robust evidence of the benefits of thi

intervention in improving patients’ health outcomes, and any significant adverse effects. The 

evidence for these issues was derived from questions 3 and 4. 

Appendixes and Evidence Tables for this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/famhistimprov/famhimp.pdf.

117 
sectional studies were potentially subject to

outcomes: it is possible that some participan

 information bias, in relation to both exposures and 

ts knew their FH more accurately because they were 

affected by the condition in question, and most all studies, the strength of 

association between FH and disease frequency was assessed at a population level, using relative 

risks, odds ratios, and related metrics. However, assessing the utility of FH for risk assessment in 

ind

en FH to develop a disorder compared to those who do not have the FH. Rather, 

the n 

e 

e issue 

ough some analyses covered a 

wide range of FH definitions, we observed that most studies defined FH largely in terms of first 

degre y 

fe

th

A pragmatic approach wa finitions. For example, 

rather than separating out mutually exclusive FH categories (e.g., ‘affected brother only’ versus 

‘aff at 

ing 

 in 

ich needs to be considered, is whether the way in which FH was captured 

in t e 

ation. 

The factors influencing accuracy of reporting were examined as part of Q2. 

 vice versa. In al

ividual patients requires examination of discriminatory accuracy metrics: sensitivity, 

specificity, and predictive values. The question is not so much ‘how many times more likely” are

people with a giv

question is more of the nature, ‘What is the chance that, given this FH, this person will go o

to develop this disease in the time period of interest?” Even for the most common complex 

disorders, most people ‘at risk’ do not actually go on to develop the disease, therefore even larg

relative risks may actually be associated with very small absolute risks over a 5 or 10 year 

period. 

Even though most studies included did not report predictive metrics, or were not even 

designed to address Q1, it was still possible to extract sufficient data to begin to explore th

of interest. We examined FH definitions in longitudinal and cross-sectional studies, appreciating 

that they provided different insights: the former are designed to address prediction of future 

disease, and the latter reflect screening for current disease. Alth

e relatives (1DRs), and only a few drew in information on a broader set of relatives. Ver

w reports provided a rationale for the specific FH definition, and it was not possible to assess 

e value of criteria such as age of onset or lineage in any meaningful way. 

s used in approaching individual FH de

ected brother and sister’) for analysis, we combined categories and compared presence of th

FH characteristic versus absence of that FH characteristic (e.g., ‘affected brother, irrespective of 

status of other relatives’ versus ‘no affected brother, irrespective of status of other relatives’). 

This permitted the assessment of that single FH characteristic (‘affected brother’ or ‘unaffected

brother’) as if it were the only question that a health professional asked the patient, thus allow

some sense of its predictive ability as a simple screening or triage question in and of itself. 

Overall, the discriminatory accuracy was generally modest, for most FH definitions used

isolation. This is not surprising – as noted previously, complex disorders do not have a strong or 

highly penetrant genetic component, and therefore it would be illogical to expect a very high

predictive value for FH, however defined. Also not surprisingly, the most sensitive FH 

definitions were usually those, which were very loose, (e.g., a minimum of one affected relative, 

whether or not further specified). From a theoretical perspective, it would be expected that a 

simple, loose definition such as this would have highest chance of picking up people genuinely at

high risk, but would also identify many false positives. The more elements required to define 

‘positive’ FH, the less sensitive and more specific the definition, again to be expected. 

Another factor, wh

hese studies was reflective of routine clinical practice. For some studies, for example, th

multigenerational cohort studies, it is clear that FH ascertainment was in no way typical of 

primary care practice. However, many of the definitions were simple and probably reflect the 

types of answers that would be received even if elicited verbally as part of an office consult

118 
As part of this review, we developed a notional categorization system (Table 2) to reflect the

effort required to obtain the minimum information implied by any given FH definition. We 

wished to take account of the time constraints under which many primary care practitioner

work, and the possible limitations of immediate knowledge, which patients might bring to a 

consultation. The use of electronic medical records (EMR) might permit the easy assembly of 

more extensive FH and render the distinctions in the table irrelevant. Also, decision-suppo

systems based on EMRs would facilitate the implementation of FH scoring systems, which 

represent the next ‘step up’ in FH assessment, taking into account information on factors such as 

family size, time at risk, etc.173 In contrast, a practitioner who may only have time to use a few 

‘screening questions’ might be well served by knowing the absolute minimum level of 

information that needs to be elicited for a given level of predictive accuracy. While the category 

A-E framework is not intended to be definitive, we were able to provide some evidence tha

type of a

s 

rt 

t this 

pproach might be useful. For example, for prevalence studies of diabetes, the AUC 

valu and 

e. However, if a 

pos

t 

on 

wit

ent 

ary 

ic (lack of disease in 

relatives is correctly identified). 

e for category D showed no improvement in discriminatory accuracy over categories B

C. If these observations are valid, it would indicate that simple, targeted questions about first 

degree relatives would be as informative as more extensive enquiry for identifying individuals at 

risk of undiagnosed diabetes. While these analyses can only be regarded as preliminary, they

suggest an approach for future research. 

Having gained some insight into the performance of specific FH definitions in predictive 

chronic diseases, the appropriate question is to ask next, is how they perform when considered 

with information on other risk factors. Depending on the disease in question, a clinician is 

unlikely to disregard other risk factors and base a risk assessment on FH alon

itive FH significantly improved the predictive ability of other established factors, then it 

might make the difference in the choice of preventive interventions, and/or in promoting risk 

reducing health behaviors. It was beyond the scope of this review to model the incremental 

predictive value of particular FH definitions combined with other risk factor variables, but this 

would be a logical extension of this enquiry. 

It is impossible to draw an overarching conclusion from the analyses conducted for Q1, and i

was not possible to assess the performance of FHs across a range of disorders. The tables 

detailing predictive value alongside disease prevalence were constructed to permit comparis

h different clinical contexts, and to give a sense of the highest likely achievable predictive 

utility, within the constraints of the data. In considering these data, it is necessary to clarify the 

underlying prevalence of the condition in the population of interest, whether the purpose is 

stratification of future disease risk (and the time frame) or triaging for screening for curr

disease, and the way in which FH information may or may not be combined with other risk 

factor information for a holistic assessment of an individual patient. 

Q2. What is the Accuracy of the Family History, and Under

What Conditions Does the Accuracy Vary? 

In order for FH to be of value in clinical decision making, patients must possess, and prim

care practitioners be able to ascertain, accurate family health information. Assessing accuracy 

requires a clear idea of an appropriate gold standard—what patients ‘should’ know, and what 

clinicians ‘should’ be able to obtain. In simple terms, an ‘accurate’ FH could be considered to be 

one which is sensitive (disease in relatives is correctly identified) and specif

119 
In order to fully explore the question of accuracy of reporting we did not restrict the 

population to those within a primary care setting as we correctly anticipated that there would

few accuracy studies within this population. In this regard, the majority of studies evaluated 

subjects with the disease or first degree relatives (1DRs) who are by definition at high risk. 

Overall, the applicability of these findings from specialized clinical settings to primary care 

settings may be limited; the high risk of spectrum bias would tend to cause overestimation in 

accuracy. Although, the attributes of the probands (or informants) were described, those of t

relatives (for example, gender or even the relation to the proband) were not, particularly in 

studies within the mental health area. 

Overall, the few rigorous studies, which fully evaluated accuracy consistently, sugge

informants are more accurate in identifying which relatives are free of the disease (specificity) 

than in identifying relatives who have been affected by cancer (sensitivity). This trend was 

generally consistent across all disease groups, except heart disease; there was some variation 

the rates for sensitivity. For example, in the mental health area, rates of sensitivity were 

consistently very low (>40) but in cancer FH they were higher (~ 80 percent). Similarly, in tho

studies that reported sensitivity for both cases and controls, there is variation between the 

different disease areas; for example, sensitivities in relatives of controls probed for Parkinson’

disease were much lower than those obse

 be 

he 

sted that 

in 

se 

s 

rved in assessments of controls in breast cancer studies 

at 

ld 

t 

ore complete information on their FH after their 

init

be 

re 

s 

ust 

s). It was challenging to 

isentangle medical history and FH in some of the studies within mental health; similarly, in this 

ar

ev

i presence of 

disease with

e 

Our findings also suggest that FH reporting may be more accurate for 1DRs than second 

degree or beyond, although few studies examined accuracy in the latter. Similarly, attributes of 

the informants and relatives have not been consistently evaluated; in those limited studies th

did examine this factor, there was no clear pattern in the attributes of the informant or those of

the relative that influence accuracy results. The methods used to collect FH and the disease 

category is likely to account for this inconsistency. We also have little insight into which 

informant characteristics are associated with more accurate reporting; future evaluations cou

consider formally examining factors such as sex, age, and cultural background. It is possible tha

informants affected by cancer may seek out m

ial diagnosis, but we were unable to confirm this within this literature. 

The accuracy of reporting by probands, members of the population or relatives cannot 

completely separated from the performance of tools to gather such data. We observed great 

variation in methods used to collect FH that ranged from simple dichotomous questions, to mo

complex standardized tools that had established psychometric properties. In the area of mental 

health, FH is an important component in establishing the presence of disease, and as such wa

included in both the index test and the reference standard; that is the FH of the relative (not j

medical history) formed part of the case definition of what was also collected in order to 

establish the presence of the disorder (for example in bipolar disorder

d

ea FH included a broader conceptualization which included relatives such as “spouses”. Future

aluation within mental health studies would be strengthened by clarifying these differences. 

Most stud es evaluating accuracy used a multimodal approach to establishing the

in the relatives. In part, this was necessitated by the status of the relatives; for 

example, clinical examination could only be undertaken in relatives that are alive. As such, there 

will always be a high risk of bias for differential verification irrespective of the different diseas

categories evaluated. It is impossible to comment on which gold standard is ‘best’ for judging 

accuracy, but we recognize that multiple strategies are necessary to capture the status of all 

relatives. 

120 
Future efforts to improve accuracy of reporting would be improved by explicit consid

of whether sensitivity or specificity is the primary goal, which is dependent on the clinical 

context and purpose of a FH oriented strategy. For example, maximizing sensitivity prioritize

the goal of missing as few ‘at risk’ family histories as possible, and is consistent with a polic

which the potential benefits from finding potential cases carry more weight than the potentia

costs and harms of investigating individuals or families with false positive histories. In contras

maximizing specificity prioritizes avoiding the potential costs and harms of false positives, and 

consistent with a policy that directs limited resources towards only identifying individuals o

families with the greatest likelihood of

eration 

s 

y in 

l 

t, 

is 

r 

 being at significant disease risk, at the cost of missing 

som

ether 

 a 

 a 

f 

tivity in 

that

ns 

se 

ice. Anonymous telephone-based risk assessment services may attract patients already 

aware of their strong family histories (and/or other risk factors) due to concerns about insurance 

e true positives. 

In general, we might expect that the accuracy of FH reporting will improve in future, as 

current initiatives lead to more awareness on the part of the general public. It is not clear wh

this will be countered by the effect that increased population mobility has on people’s abilities to

keep up to date with the health of more distant family members. 

Q3. What is the Direct Evidence That Routinely Getting

Family History Will Improve Health Outcomes for the Patient 

and/or Family? 

AND 

Q4. What is the Direct Evidence That Routinely Getting

Family History Will Result in Adverse Outcomes for the 

Patient and/or Family? 

These two research questions were identified as being complementary, and were therefore

approached together in this discussion. 

While the literature contains many observational studies examining the association between 

awareness of familial disease risk and patient risk behavior, psychological distress and uptake o

services (see Webtable 30 for list of observational studies) they do not identify the temporal 

sequence from risk awareness to change in relevant outcomes. Thus, they do not provide clear 

evidence that family history collection and/or risk identification as a deliberate clinical ac

itself leads to changes in health outcomes. As demonstrated in the review, there is very limited

information available from such robust intervention studies. 

The focus of this review was to inform primary care practice, and we identified few studies 

conducted in a general population or non-specialist context. This is not surprising, considering 

 when familial risk assessment is offered to general populations (not specially selected for 

risk), the response rate is usually low. In the reviewed studies, the FH collection interventio

were predominately integrated in multifactorial risk assessment tools particularly in the two 

studies examining improvements in health outcomes (Q3). Although these studies were not in a 

primary care office setting, they did approach the general population through respondentinitiated enquiry. These models suggest that the modality of risk assessment may affect the u

of this serv

121 
disc

the 

nt 

e adverse effects of FH collection and risk assessment (Q4), only three 

sma

individuals are aware that 

ey are at low familial risk, confirmation of status on familial risk assessment would be 

exp

g

p

However, to fully assess the psyc llection and use as an approach to 

chronic disease risk prediction, validated context-specific tools need to be developed. Further, 

other than psychological distress, studies of o erse outcomes were not identified (e.g., 

reduction in screening behavior).130

Finally, it is important to note that, even if FH collection and risk assessment had a positive 

net 

redu

Q5. What are the or Discourage 

r 

nterpretation of the data. 

, 

e 

is 

ion, 

 (e.g., 

rimination. This may be particularly the situation if the assessment is associated with 

similarly anonymous telephone based genetic counseling. However, in patients unaware of 

implications of their FH, in-office assessment followed by their personal physician’s 

recommendation may be the preferred option. 

Irrespective of the mode and type of FH assessment, the impact on risk-reducing behavior 

remains unclear. We identified evidence that suggests that incorporating FH collection into 

multifactorial risk assessment increased screening rates for breast cancer risk, but direct evidence 

for other conditions is lacking. Incorporating FH collection into a multifactorial risk assessme

tool leads to difficulties in disentangling the effect of the FH intervention from other factors. 

When considering th

ll studies were identified. They suggest that FH collection and risk assessment increases 

general anxiety in the short term, with scores returning to pre-intervention levels by 6 to 12 

weeks. While the short term impact of intervention is increased anxiety, the process of reviewing 

the FH may also reassure the clinic attendees. On the other hand, if 

th

ected to make no difference to the score. To some extent, these findings mirror those of 

enetic testing for adult onset disorders, in which the consistent finding is that genetic test results 

rovoke short-term increases in anxiety which return to baseline levels within 1-2 months.174,175 

hological effect of FH co

ther adv

effect on risk reducing behavior, this does not provide evidence that the prescribed riskcing behavior leads to improved health outcomes. 

 Factors That Encourage

Obtaining and Using a Family History? 

Although ‘taking a FH’ is a core activity in primary care,176 little is known about the factors 

that encourage or inhibit it. We identified only a few studies that addressed this question and 

they were very heterogeneous and did not provide a clear understanding of the factors that 

improve the appropriate collection and use of FH information in non-specialist settings, whethe

for general application in complex disease risk assessment or screening patients with more 

evident familial disease who require more focused FH collection. In many cases FH collection 

and use is presented as a dichotomized variable, limiting the i

Despite the difficulty of synthesizing these studies, some observations are possible. To do so

it is necessary to consider together studies which examined the likelihood that FH was discussed

with those which examined whether FH was recorded in patient records as a proxy for the sam

underlying activity, (i.e., that FH was collected, recorded, and acted upon). On this basis, there 

tentative evidence to support the importance of: 1) patient factors such as gender, age, educat

their ethnic group, the nature of their health insurance, 2) provider factors such as younger or 

older practitioners, whether or not they were residency-trained, 3) the condition of interest

the FH of some cancers appears more likely to be reviewed than other conditions), and 4) the 

context, including whether the consultation focuses on a specific disease or not, physical 

122 
examinations, whether or it is a new patient consultation, whether or not the patient brings

specific disease concerns. 

There is insufficient evidence on whether organizational factors such as electronic

records, make a meaningful difference to FH ca

 health 

pture or recording. In a previous review,145 we 

not

 in 

he 

e cannot consider that these methods 

necessa

prac f 

data points availa ve an indication 

onl of the possib finitive 

ana

 family 

ed that the use of FH tools was associated with more accurate and complete recording of FH

information than non-systematic approaches, but it is not clear whether providing such tools

itself promotes their routine use. 

Limitations 

The studies reviewed in this report were limited to those published in English; however, t

impact of any language bias is offset by the optimal applicability to English speaking countries 

for which this report was prepared. Given the scope of the research questions, we limited our 

search from 1995 to March 2009. We acknowledge that the 1995 publication date cutoff may 

have excluded some studies.177,178 Similarly, due to restraints of time and resources, grey 

literature was explored in a limited manner. 

In considering the elements of FH which provide most value in predicting risk of disease 

(Q1), we re-analyzed data for a large number of studies, most of which were not primarily 

designed to address the goals of this review. We took at face value the definitions of FH as they 

were described in the source reports, and did not contact authors for confirmation. Neither did 

we attempt to assess the likely accuracy of FH reporting, nor take into account the method by 

which it was collected (although t is h was noted as a descriptive item). We grouped together data 

from studies that were very heterogeneous, in terms of study population and definitions of 

disease outcome. While almost all studies indicated that FH information was captured by 

structured interview or self-completion questionnaire, w

rily replicate the quality of information that might be obtained by a primary care 

titioner in a clinical setting. Finally, the AUC calculations were restricted by the number o

ble. The findings presented should therefore be considered to gi

y le predictive ability of different FH items, rather than to be a de

lysis. 

In the context of accuracy (Q2), we did not restrict studies according to the manner in which

FH was collected and considerable variation in the methods used was observed. Almost 

universally, studies included the collection of FH based on self-reporting (from either the 

proband, informant, or relative) and are therefore dependent on the individual respondents’ 

knowledge of their history. This represents a limitation on FH taking in practice rather than a 

limitation specifically of this systematic review. Additionally, eligible studies evaluating the 

accuracy of FH reporting did not use the same method to ascertain FH or verify status within all 

relatives. As such, interpretation of the metrics of accuracy was limited to the methods of FH 

ascertainment and verification used in these studies. Finally, when evaluating and comparing 

quality of studies, we assumed the index and reference tests were similar. 

 In examining the effects of FH taking on behavior (Q3) and adverse effects (Q4), the review 

was limited to populations and setting applicable to primary care. We acknowledge that 

systematic FH collation and interpretation in specialist setting may provide evidence relevant to 

primary care but the scope and pragmatic considerations limited the focus of the review. The 

emphasis on very specific clinical behavioral outcomes also does not allow for exploration of 

other effects on the part of patients, such as seeking out more extensive information from

123 
members as a result of having been asked “the first” set of questions on FH. Further explora

of the ethico-legal and socia

tion 

l aspects would have added a valuable perspective to the review, but 

ther ort 

s 

s; however, we determined that incorporating a comparison of 

ols, in addition to the original questions, was not feasible, and altered the already broad focus 

of the review. FH tools for cancer have revious AHRQ systematic 

review,145 this review identified several -181 Another systematic review has 

also

s, 

 one 

eadily 

to the primary care practitioner. 

itions, 

 be 

e be 

very high risk 

d, 

e was limited information in the quantitative literature; it was beyond the scope of this rep

to examine the extensive and diverse qualitative literature that may have explored these aspects

of FH. 

In consultation with our TEP and partners, we considered the issue of how different FH tool

might relate to the review question

to

 been examined in a p

 generic FH tools.179

 examined cancer and generic tools applicable to primary care settings.146

Conclusion 

Firstly, we explore the implications of the individual questions. 

1. The main analysis drew on data from studies designed to address other primary question

but yielded some useful quantitative information, which indicates the likely upper limit on 

predictive utility of different FH definitions for the diseases of interest, where FH is used in 

isolation as a risk factor. The analysis was constrained by the definitions of FH used in the 

primary studies, but we developed a notional approach to categorizing FH definitions to assist 

interpretation of their workload impact in routine clinical settings. In and of themselves, very few 

of the specific FH items or combinations examined had more than modest ability to predict

future disease risk in individuals. In general, the least constrained definitions (e.g., at least

affected 1DR, with no other information required) were generally associated with higher 

sensitivities and lower specificities. This conclusion is not surprising, since a very high 

predictive ability based on FH alone would imply a disorder with a strong genetic element and 

high penetrance. For complex disorders, even modest independent discriminatory ability might 

provide clinically useful predictive information in combination with other risk indicators r

available 

It is worth noting the importance of considering the complexity of the FH definition itself 

and its relationship with the type of risk information it conveys. The most complex defin

particularly those which incorporate lineage (Category E, Table 2, Chapter 2), appeared to

designed to identify Mendelian-type patterns of inheritance.182 As such, they would therefor

expected to identify rare population subgroups with a “genetic version” of a complex disorder.

Such an approach is, by definition, likely to be highly specific and but rather insensitive. In 

contrast, a positive FH based on a very simple definition might provide a marker which picks out

a higher than average ‘familial loading’ for a disorder, but has no need to consider detailed 

pedigree information. This approach would be characterized by higher sensitivity but lower 

specificity. The purpose of the FH assessment in primary care (to pick out 

subgroups for further genetic assessment or to work out more general familial disease loading) 

merits further discussion. 

Recommendations for direction of future research: 

• Further clarification of the purpose of FH taking in primary care settings is require

so that future assessments of the utility of FH are based on an explicit distinction 

between, for example, disease risk assessment as part of routine preventive care (e.g., 

124 
the routine physical examination) in which other risk information is taken into 

account, triage for screening (e.g., selecting people for formal tests of glucose 

tolerance), or applying genetic referral/testing guidelines in patients who appear to 

have a prominent familial disease history, in whom genetic disease is suspected. 

• The evidence base requires studies designed explicitly for the purpose of examining 

ich 

• FH items should be formally examined alongside other recommended or readily 

accessible risk factors, in or tent to which they provide useful 

independent and/or incremen ility. 

. The accuracy of self reported FH has implications for the correct risk assessment and 

man

ude 

e 

 studies 

ffective mental health disorders, cardiovascular 

e 

vels 

ant, 

s to improved health outcomes. Concurrent qualitative studies should 

the predictive ability of combinations of individual FH items. This requires 

adequately powered, longitudinally designed studies in which detailed, extensive, 

clearly defined and documented FH components comprise the ‘exposures’, in which 

participants are followed up for a period which is clinically meaningful, in wh

adequate measures are taken to control bias, and in which the primary metrics relate

to individual risk prediction. 

der to identify the ex

tal discriminatory ab

2

agement of patients. Accuracy of FH reporting appears to be dependent on the method of 

collection, which is related to the disease area. Accurate reporting of the absence of disease

(specificity) appears to be greater than accurate reporting of presence of disease (sensitivity) 

across different disease areas. Estimates of sensitivity show greater variation and the magnit

varies with different diseases. Although, there is limited evidence, accuracy of recall and 

reporting may be influenced by both patient and informant (relative) factors, and by the method 

used to collect FH. 

Recommendations for direction of future research: 

• Future studies in accuracy should be undertaken in populations reflective of th

primary care setting and representative of the spectrum of disease risk. Future

should endeavor to better characterize the attributes of the informant/proband and 

especially the relatives; the potential of these factors to influence the accuracy of 

reporting should be consistently evaluated. Future evaluation should be undertaken in 

the areas of asthma and atopy, a

diseases, and diabetes. 

3. Within primary care populations, there is very limited evidence to support or refute the 

effect on risk-reducing behavior changes (e.g., lifestyle changes or uptake of recommended 

clinical interventions) of taking a FH and using it to personalize risk of developing respective 

conditions. 

Recommendations for future research: 

• Well-designed trials are required that compare FH-based, personalized risk advic

with standard of care on risk reducing behaviors in populations at different risk le

(including population risk). The outcomes of interest need to be clinically relev

either leading to improved mortality or morbidity or surrogate measures with strong 

evidence of link

also be considered. 

• Proposed trials should be based on evidence from systematic reviews to ensure that 

prescribed risk-reducing behaviors are evidence-based. 

125 
4. In primary care populations, there is very limited information to evaluate direct harm

urred from the routine practice of taking FH and using it to personalize risk information

Recommendations for future research: 

• Trials of FH taking as an intervention should include capture of data to examine th

inc . 

e 

oncurrent 

s 

 the 

factors th of 

FH lection and discussion of FH 

y the population and practitioners, with no factors identified that are associated with the use of 

the ely 

ure that 

hich may be encountered. The most important studies are those which 

are practice, including highlighting 

s

f 

n of 

gs. 

e 

is not absence of effect. The few studies that have examined potential harms of FH 

taki nfounded, and should not hinder the development of 

e 

from

cap

sug

pu

clin

im ntial of the FH” in primary 

care practice.183 The systematic and often graphical collation of this information (e.g., as 

full range of potential impacts on individuals of FH collection and implementation 

strategies based on familial risk identification, both negative and positive. C

qualitative studies should also be considered. Baseline data on psychological status

should be captured so that this can formally be adjusted for use in outcome analyses. 

To enable appropriate evaluation of psychological harm, context-specific measure

need to be developed and validated. 

 

5. In order to assess the content validity of systematic FH tools we need to know not only

at affect the recall of FH (Q2) but also those factors that affect the collection and use

. Thus far, in this population, there is limited information on col

b

FH. There is some suggestion that populations from underserved communities are less lik

to report and have the opportunity to discuss FH, but the level of evidence is weak. 

Recommendations for future research: 

• Further research is required to clarify the most important patient and practitioner 

factors that may affect the collection and use of FH. This likely requires the 

development of theoretical frameworks to guide appropriate design, and to ens

methodologies adequately address the many potential biases and interactions between

factors, w

address factors directly relevant to primary c

patient factors which promote inequity in the application of effective intervention

• Where inequities are identified, interventions should be designed to ameliorate these 

factors in future trials and service provision. Such research could include analyses o

national population and practitioner survey databases. 

• While research should focus on clinically relevant outcomes, it should also include 

process evaluations to identify factors, which affect the successful implementatio

the FH interventions. 

The findings of this systematic review pose as many questions as they answer, but they do 

not undermine the general view that FH taking is a worthwhile activity in primary care settin

The evidence base for FH-based assessment and intervention is not well-developed, but absenc

of evidence 

ng suggest that such concerns may be u

rigorous evaluations of FH taking and FH-based risk interventions. There is consistent evidenc

 a previous report145 that FH tools (albeit for cancer) promote higher quality information 

ture than non-systematic approaches. The findings from this systematic review begin to 

gest how to choose FH items to populate tools and emphasize the importance of considering 

rpose (to what use will FH information be put?) and context (time available, and nature of 

ical encounter). 

Finally, although this systematic review identified the paucity of relevant evidence for many

portant issues, the findings do not negate the “extraordinary pote

126 
127 

gen

def amily practice, in particular, is characterized by the 

wo

inform

an

ograms) in family-oriented clinical practice may be used for purposes which go beyond 

specific disease risk assessment, for example to assess the impact of “family health” (broadly

ined) on an individual’s well-being.184 F

continuity of the relationship between, patients, families, and practitioners. Thus, in the real 

rld, FH may be pieced together over time and decision-making may be incremental as more 

ation emerges. A deeper appreciation of the context in which FH is captured, interpreted, 

d acted upon is important as further FH based interventions are developed and evaluated. 

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n aid: 

th 

 182. ning 

e of 

istory. [Review] [40 refs]. Br Med 

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 184. 

gerWilliams KP, Sheppard VB, Todem D, et

Family matters in mammography screening 

among African-American wom

than or equal to]40. J Natl Med Assoc 

2008;100(5):508-15. 

Gil F, Mendez I, Sirgo A, et al. Perceptio

breast cancer risk and surveillance 

of women with fami

a brief report on a Spanish cohort. 

Psychooncology 2003;12(8):821-7. 

Helfand BT, Loeb S, Cashy J, et al. Tumor 

characteristics of car

the deCODE 8q24 prostate cancer 

susceptibility alleles. J Urol 

2202;179(6):2197-201. 

 164. Longacre AV, Cramer LD, Gross CP. 

Screening colonoscopy use among individua

at higher colorectal cancer risk. J Clin 

Gastroenterol 2006;40(6):490-

 165. Shah M, Zhu K, Palmer RC, et al. Family 

history of cancer and utilization of prostate, 

colorectal and skin cancer screening tests in 

U.S. men. Prev Med 2007;44(5):459-64. 

Petrisek A, Campbell S, Laliberte L. Family 

history of breast cancer: impact on the dis

experience. Cancer Pract 2000;8(3):135-

Madlensky L, Flatt SW, Bardwell WA, et al. 

Is family history related to preven

behaviors and medic

cancer patients? Breast Cancer Res Treat 

2005;90(1):47-54. 

Andersen MR, Peacock S, Nelson J, et al

Worry about ovarian cancer risk and use of 

ovarian cancer screening by women at ri

ovarian cancer.[see comment]. Gynecol On

2002;85(1):3-8. 

Bloom JR, Stewart SL, Oakley-Girvans I, e

Family history, perceived risk, and prostate 

cancer screening among A

men. Cancer Epidemiology Biomarkers

Prevention 2006;15(11):2167-73. 

Cotter MP, Gern RW, Ho GY, et al. Role of 

family history and ethnicity on the mode and 

age of prostate cancer presentation. Prostate 

2002;50(4):216-21. 

 171. Bennett RL. The practical guide to the genetic 

family history. New York: John Wiley; 1999. 

Wattendorf DJ, Hadley DW. Family history: 

The three-generation pedigree. Am

Physician 2005;72(3):441-8. 

Silberberg J, Fryer J, Wlodarczyk J, et al. 

Comparison of family history measures use

identify high risk of coron

Genet Epidemiol 1999;16(4):344-55. 

Janko

and functional impact of DNA testing on 

patients with symptoms of Huntington's 

disease. J Med Genet 1995;32(7):516-8. 

Marteau T, Senior V, Hu

Psychological Impact of Genetic Testing fo

Familial Hypercholesterolemia Within a 

Controlled Trial. Am J Med Genet 

2004;128A:285-93. 

 176. Qureshi N, Modell B, Modell M. Timeline: 

Raising the profile of genetics in primary ca

[Review] [55 refs]. Nature Reviews Genetics

2004;5(10):783-90. 

 177. Waern U, Hedstrand H, Aberg H. What 

middle-aged men know of their parents' cause

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Williams RR, Hunt SC, Barlow GK, et al

Health family trees: a tool for find

helping young family members of coronary 

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Qureshi N, Bethea J, Modell B, et al. 

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evaluating a new family history tool. Fam 

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Frezzo TM, Rubinstein WS, Dunham D

The genetic family history as a risk assessment

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Combining risks estimations and clinical 

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Technol Inform 2003;95:525-30. 

Pharoah PD, Stratton JF, Mackay J. Scree

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Bull 1998;54(4):823-38. 

Qureshi N. Summary of WONCA 98 

workshops: family doctors talk genetics. 

European Journal of General Practice 

1999;5(1):33-4. 

McDaniel SH, Campbell TL, Seaburn DB. 

Family-oriented primary care: a manual for 

medical providers. New York: Sprin

Verlag; 1990. 
Appendix A – Search Strategies Detailed 

Main Review

Medline 

1. Ambulatory care/ 

2. ambulatory care.tw. 

3. Primary health care/ 

4. Physicians, family/ 

5. Family practice/ 

6. primary health care.tw. 

7. primary healthcare.tw. 

8. primary care.tw. 

9. general practi*.tw. 

10. family practic*.tw. 

11. (family adj2 (physician? or doctor? or clinic?)).tw. 

12. family medical care.tw. 

13. gp.ti,ab. 

14. Community health services/ 

15. or/1-14 

16. exp Pedigree/ 

17. limit 16 to humans 

18. Medical History Taking/ 

19. Genetic Predisposition to Disease/ 

20. anamnesis.ti,ab. 

21. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti. 

22. (human adj2 pedigree).ti,ab. 

23. Family Health/ 

24. (family history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

25. (familial history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

26. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

27. ((first or second) adj2 degree relative?).ti,ab. 

28. ((parental or paternal or maternal) adj2 history).ti. 

29. or/17-28 

30. (sensitivity or specificity).ti. 

31. (accura$ or inaccur$ or valid$ or reliability).ti. 

32. under reporting.ti. 

33. underreporting.ti. 

34. exp "Reproducibility of Results"/ 

35. completeness.ti. 

36. consistency.ti. 

37. or/30-36 

38. Risk factors.ti. 

A-1
39. *risk factors/ 

40. or/38-39 

41. family history.tw. 

42. 41 and 40 

43. exp Stroke/ge, ep, pc, et [Genetics, Epidemiology, Prevention & Control, Etiology] 

44. (stroke$ or cerebrovascular$ or cerebral vascular or CVA$).ti. 

45. ((cerebral or cerebellar or brainstem or vertebrobasilar) adj5 (infarct$ or isch?emi$ or 

thrombo$ or apoplexy or emboli$)).ti. 

46. ((cerebral or intracerebral or intracranial or parenchymal or brain or intraventricular 

or brainstem or cerebellar or infratentorial or supratentorial or subarachnoid) adj 

(haemorrhage or hemorrhage or haematoma or hematoma or bleeding or 

aneurysm)).ti. 

47. or/43-46 

48. Asthma/ge, pc, et, ep [Genetics, Prevention & Control, Etiology, Epidemiology] 

49. (asthma or atopy or atopic).ti. 

50. or/48-49 

51. Depression/pc, ep, ge, et [Prevention & Control, Epidemiology, Genetics, Etiology] 

52. Depressive Disorder, Major/pc, ep, et, ge [Prevention & Control, Epidemiology, 

Etiology, Genetics] 

53. (involutional adj2 (depress$ or psychos$ or melancholia)).ti. 

54. ((major or chronic) adj2 depress$).ti. 

55. or/51-54 

56. exp Diabetes Mellitus, Type 1/ge, ep, pc, et [Genetics, Epidemiology, Prevention & 

Control, Etiology] 

57. Diabetes Mellitus/et, pc, ge, ep [Etiology, Prevention & Control, Genetics, 

Epidemiology] 

58. exp Diabetes Mellitus, Type 2/ge, ep, pc, et [Genetics, Epidemiology, Prevention & 

Control, Etiology] 

59. (diabetes or diabetic?).ti. 

60. or/56-59 

61. ((breast or ovar$ or prostate or colon or colorectal or lung) adj3 (cancer$ or 

neoplasm$ or carcinom$ or tumo?r$)).ti. 

62. exp Breast Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention & 

Control] 

63. exp Colorectal Neoplasms/ge, pc, et, ep [Genetics, Prevention & Control, Etiology, 

Epidemiology] 

64. exp Ovarian Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention 

& Control] 

65. exp Prostatic Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention 

& Control] 

66. exp Lung Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention & 

Control] 

67. or/61-66 

68. exp Cardiovascular Diseases/pc, ge, ep, et [Prevention & Control, Genetics, 

Epidemiology, Etiology] 

69. chd.ti. 

A-2
70. thrombo$.ti. 

71. ((coronary or heart or cardiovascular) adj2 disease?).ti. 

72. or/68-71 

73. 60 or 55 or 72 or 50 or 67 or 47 

74. 15 or 37 or 73 

75. 74 and 29 

76. 75 or 42 

77. (note or comment or editorial or letter or congresses).pt. 

78. 76 not 77 

79. animals/ not (humans/ and animals/) 

80. 78 not 79 

81. limit 80 to english language 

82. limit 81 to yr="1995 - 2008" 

EMBASE 

1. general practice/ or primary medical care/ or private practice/ 

2. exp ambulatory care/ or exp primary health care/ 

3. general practitioner/ 

4. exp community care/ 

5. ambulatory care.tw. 

6. primary health care.tw. 

7. primary healthcare.tw. 

8. general practi*.tw. 

9. family practi*.tw. 

10. primary care.tw. 

11. (family adj2 (physician? or doctor? or clinic?)).tw. 

12. family medical care.tw. 

13. gp.ti,ab. 

14. or/1-13 

15. "sensitivity and specificity"/ 

16. exp Validity/ 

17. exp Reproducibility/ 

18. (sensitivity or specificity).ti. 

19. (accura$ or inaccur$ or valid$ or reliability).ti. 

20. under reporting.ti. 

21. underreporting.ti. 

22. consistency.ti. 

23. completeness.ti. 

24. or/15-23 

25. family history/ 

26. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti. 

27. (human adj2 pedigree).ti,ab. 

28. (family history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

29. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

A-3
30. ((first or second) adj2 degree relative?).ti,ab. 

31. ((parental or paternal or maternal) adj2 history).ti. 

32. or/25-31 

33. *risk factor/ 

34. risk factor?.ti. 

35. or/33-34 

36. family history/ 

37. family history.tw. 

38. or/36-37 

39. 38 and 35 

40. exp Asthma/ 

41. (asthma* or atopy or atopic).ti. 

42. Atopy/ 

43. or/40-42 

44. endogenous depression/ or involutional depression/ or major depression/ 

45. (involutional adj2 (depress$ or psychos$ or melancholia)).ti. 

46. ((major or chronic) adj2 depress$).ti. 

47. or/44-46 

48. exp Diabetes Mellitus/ 

49. (diabetes or diabetic?).ti. 

50. or/48-49 

51. exp Breast Cancer/ 

52. exp Ovary Cancer/ 

53. exp Prostate Cancer/ 

54. exp Colorectal Cancer/ 

55. exp Lung Cancer/ 

56. ((breast or ovar$ or prostate or colon or colorectal or lung) adj3 (cancer$ or 

neoplasm$ or carcinom$ or tumo?r$)).ti. 

57. or/51-56 

58. exp cardiovascular disease/ 

59. chd.ti. 

60. thrombo$.ti. 

61. ((coronary or heart or cardiovascular) adj2 disease?).ti. 

62. (stroke$ or cerebrovascular$ or cerebral vascular or CVA$).ti. 

63. ((cerebral or cerebellar or brainstem or vertebrobasilar) adj5 (infarct$ or isch?emi$ or 

thrombo$ or apoplexy or emboli$)).ti. 

64. ((cerebral or intracerebral or intracranial or parenchymal or brain or intraventricular 

or brainstem or cerebellar or infratentorial or supratentorial or subarachnoid) adj 

(haemorrhage or hemorrhage or haematoma or hematoma or bleeding or 

aneurysm)).ti. 

65. or/58-64 

66. 57 or 47 or 65 or 50 or 43 

67. 24 or 14 or 66 

68. 67 and 32 

69. 68 or 39 

70. limit 69 to human 

A-4
71. limit 70 to english language 

72. (conference paper or editorial or letter or note or proceeding).pt. 

73. 71 not 72 

74. limit 73 to yr="1995 - 2008" 

CINAHL 

1. Primary Health Care/ 

2. primary health care.tw. 

3. primary healthcare.tw. 

4. primary care.tw. 

5. Physicians, Family/ 

6. Family Practice/ 

7. general practi*.tw. 

8. family practic*.tw. 

9. (family adj2 (physician? or doctor? or clinic?)).tw. 

10. family medical care.tw. 

11. gp.ti,ab. 

12. (family adj2 (medic* or care)).tw. 

13. Community Health Services/ 

14. or/1-13 

15. exp "Reliability and Validity"/ 

16. "Reproducibility of Results"/ 

17. (sensitivity or specificity).ti. 

18. (accura$ or inaccur$ or valid$ or reliability).ti. 

19. under reporting.ti. 

20. underreporting.ti. 

21. consistency.ti. 

22. completeness.ti. 

23. or/15-22 

24. family history/ 

25. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti. 

26. (human adj2 pedigree).ti,ab. 

27. (family history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

28. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

29. ((first or second) adj2 degree relative?).ti,ab. 

30. ((parental or paternal or maternal) adj2 history).ti. 

31. or/24-30 

32. Stroke/ 

33. (stroke$ or cerebrovascular$ or cerebral vascular or CVA$).ti. 

34. ((cerebral or cerebellar or brainstem or vertebrobasilar) adj5 (infarct$ or isch?emi$ or 

thrombo$ or apoplexy or emboli$)).ti. 

35. ((cerebral or intracerebral or intracranial or parenchymal or brain or intraventricular 

or brainstem or cerebellar or infratentorial or supratentorial or subarachnoid) adj 

A-5
(haemorrhage or hemorrhage or haematoma or hematoma or bleeding or 

aneurysm)).ti. 

36. or/32-35 

37. Asthma/ 

38. (asthma* or atopy or atopic).ti. 

39. or/37-38 

40. Depression/ 

41. (involutional adj2 (depress$ or psychos$ or melancholia)).ti. 

42. ((major or chronic) adj2 depress$).ti. 

43. or/40-42 

44. diabetes mellitus/ or diabetes mellitus, insulin-dependent/ or diabetes mellitus, noninsulin-dependent/ 

45. (diabetes or diabetic?).ti. 

46. or/44-45 

47. exp Breast Neoplasms/ 

48. exp Colorectal Neoplasms/ 

49. exp Ovarian Neoplasms/ 

50. exp Prostatic Neoplasms/ 

51. exp Lung Neoplasms/ 

52. ((breast or ovar$ or prostate or colon or colorectal or lung) adj3 (cancer$ or 

neoplasm$ or carcinom$ or tumo?r$)).ti. 

53. or/47-52 

54. exp Cardiovascular Diseases/ 

55. chd.ti. 

56. thrombo$.ti. 

57. ((coronary or heart or cardiovascular) adj2 disease?).ti. 

58. or/54-57 

59. 46 or 43 or 36 or 39 or 53 or 58 

60. 14 or 59 or 23 

61. 60 and 31 

62. limit 61 to english language 

63. limit 62 to (abstract or "book review" or commentary or doctoral dissertation or 

editorial or exam questions or letter or masters thesis or pamphlet) 

64. 62 not 63 

65. limit 64 to yr="1995 - 2008" 

psycINFO

1. cerebrovascular accidents/ 

2. (stroke$ or cerebrovascular$ or cerebral vascular or CVA$).ti. 

3. ((cerebral or cerebellar or brainstem or vertebrobasilar) adj5 (infarct$ or isch?emi$ or 

thrombo$ or apoplexy or emboli$)).ti. 

4. ((cerebral or intracerebral or intracranial or parenchymal or brain or intraventricular or 

brainstem or cerebellar or infratentorial or supratentorial or subarachnoid) adj 

(haemorrhage or hemorrhage or haematoma or hematoma or bleeding or aneurysm)).ti. 

A-6
5. or/1-4 

6. asthma/ 

7. asthma.ti. 

8. exp major depression/ 

9. (involutional adj2 (depress$ or psychos$ or melancholia)).ti. 

10. ((major or chronic or severe) adj2 depress$).ti. 

11. or/8-10 

12. diabetes mellitus/ 

13. (diabetes or diabetic?).ti. 

14. or/12-13 

15. exp Ovaries/ 

16. exp Colon Disorders/ 

17. exp Prostate/ 

18. lung disorders/ 

19. or/15-18 

20. exp Neoplasms/ 

21. cancer.ti. 

22. or/20-21 

23. 22 and 19 

24. Breast Neoplasms/ 

25. ((breast or ovar$ or prostate or colon or colorectal or lung) adj3 (cancer$ or 

neoplasm$ or carcinom$ or tumo?r$)).ti. 

26. or/23-25 

27. exp cardiovascular disorders/ 

28. chd.ti. 

29. thrombo$.ti. 

30. ((coronary or heart or cardiovascular) adj2 disease?).ti. 

31. or/27-30 

32. 11 or 26 or 31 or 14 or 6 or 7 or 5 

33. primary health care/ 

34. general practitioners/ 

35. family medicine/ 

36. family physicians/ 

37. primary health care.tw. 

38. primary healthcare.tw. 

39. primary care.tw. 

40. family practic*.tw. 

41. (family adj2 (physician? or doctor? or clinic?)).tw. 

42. general practi*.tw. 

43. family medical care.tw. 

44. gp.ti,ab. 

45. or/33-44 

46. exp statistical validity/ 

47. (sensitivity or specificity).ti. 

48. (accura$ or inaccur$ or valid$ or reliability or completeness or consistency).ti. 

49. under reporting.ti. 

A-7
50. underreporting.ti. 

51. exp statistical analysis/ 

52. psychometrics/ 

53. or/46-52 

54. or/46-50 

55. at risk populations/ or predisposition/ or "susceptibility (disorders)"/ 

56. anamnesis.ti,ab. 

57. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti. 

58. (human adj2 pedigree).ti,ab. 

59. (family history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

60. (familial history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

61. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

62. ((first or second) adj2 degree relative?).ti,ab. 

63. ((parental or paternal or maternal) adj2 history).ti. 

64. or/55-63 

65. 53 or 32 or 45 

66. 64 and 65 

67. limit 66 to human 

68. limit 67 to english language 

69. limit 68 to (abstract collection or bibliography or "column/opinion" or 

"comment/reply" or editorial or encyclopedia entry or letter) 

70. 68 not 69 

71. limit 70 to yr="1995 - 2008" 

CCTR 

1. Ambulatory care/ 

2. ambulatory care.tw. 

3. Primary health care/ 

4. Physicians, family/ 

5. Family practice/ 

6. primary health care.tw. 

7. primary healthcare.tw. 

8. primary care.tw. 

9. general practi*.tw. 

10. family practic*.tw. 

11. (family adj2 (physician? or doctor? or clinic?)).tw. 

12. family medical care.tw. 

13. gp.ti,ab. 

14. Community health services/ 

15. or/1-14 

16. exp Pedigree/ 

17. limit 16 to humans 

18. Medical History Taking/ 

A-8
19. Genetic Predisposition to Disease/ 

20. anamnesis.ti,ab. 

21. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti. 

22. (human adj2 pedigree).ti,ab. 

23. Family Health/ 

24. (family history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

25. (familial history adj3 (taking or collect$ or tool? or questionnaire? or form? or 

algorith?m or assessment)).ti,ab. 

26. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

27. ((first or second) adj2 degree relative?).ti,ab. 

28. ((parental or paternal or maternal) adj2 history).ti. 

29. or/17-28 

30. (sensitivity or specificity).ti. 

31. (accura$ or inaccur$ or valid$ or reliability).ti. 

32. under reporting.ti. 

33. underreporting.ti. 

34. exp "Reproducibility of Results"/ 

35. completeness.ti. 

36. consistency.ti. 

37. or/30-36 

38. Risk factors.ti. 

39. *risk factors/ 

40. or/38-39 

41. family history.tw. 

42. 41 and 40 

43. exp Cerebrovascular Accident/ge, ep, pc, et [Genetics, Epidemiology, Prevention & 

Control, Etiology] 

44. (stroke$ or cerebrovascular$ or cerebral vascular or CVA$).ti. 

45. ((cerebral or cerebellar or brainstem or vertebrobasilar) adj5 (infarct$ or isch?emi$ or 

thrombo$ or apoplexy or emboli$)).ti. 

46. ((cerebral or intracerebral or intracranial or parenchymal or brain or intraventricular 

or brainstem or cerebellar or infratentorial or supratentorial or subarachnoid) adj 

(haemorrhage or hemorrhage or haematoma or hematoma or bleeding or 

aneurysm)).ti. 

47. or/43-46 

48. Asthma/ge, pc, et, ep [Genetics, Prevention & Control, Etiology, Epidemiology] 

49. (asthma or atopy or atopic).ti. 

50. or/48-49 

51. Depression/pc, ep, ge, et [Prevention & Control, Epidemiology, Genetics, Etiology] 

52. Depressive Disorder, Major/pc, ep, et, ge [Prevention & Control, Epidemiology, 

Etiology, Genetics] 

53. (involutional adj2 (depress$ or psychos$ or melancholia)).ti. 

54. ((major or chronic) adj2 depress$).ti. 

55. or/51-54 

A-9
A-10

56. Diabetes Mellitus/et, pc, ge, ep [Etiology, Prevention & Control, Genetics, 

Epidemiology] 

57. exp Diabetes Mellitus, Type 1/ge, ep, pc, et [Genetics, Epidemiology, Prevention & 

Control, Etiology] 

58. exp Diabetes Mellitus, Type 2/ge, ep, pc, et [Genetics, Epidemiology, Prevention & 

Control, Etiology] 

59. (diabetes or diabetic?).ti. 

60. or/56-59 

61. ((breast or ovar$ or prostate or colon or colorectal or lung) adj3 (cancer$ or 

neoplasm$ or carcinom$ or tumo?r$)).ti. 

62. exp Breast Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention & 

Control] 

63. exp Colorectal Neoplasms/ge, pc, et, ep [Genetics, Prevention & Control, Etiology, 

Epidemiology] 

64. exp Ovarian Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention 

& Control] 

65. exp Prostatic Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention 

& Control] 

66. exp Lung Neoplasms/et, ge, ep, pc [Etiology, Genetics, Epidemiology, Prevention & 

Control] 

67. or/61-66 

68. exp Cardiovascular Diseases/pc, ge, ep, et [Prevention & Control, Genetics, 

Epidemiology, Etiology] 

69. chd.ti. 

70. thrombo$.ti. 

71. ((coronary or heart or cardiovascular) adj2 disease?).ti. 

72. or/68-71 

73. 60 or 67 or 55 or 50 or 72 or 47 

74. 73 or 15 or 37 

75. 29 and 74 

76. 75 or 42 

77. limit 76 to yr="1995 - 2008" 
Appendix B - Forms 

Level 1 – Title and Abstract Screening 

Level 2 – Title and Abstract Screening 

Level 3 – Title and Abstract NQ & BW Screening 

B-1
Level 4 – Full Text Screening 

B-2
Review Question 1: QUALITY ASSESSMENT QUESTIONS 

ALL STUDIES 

1. Was the same method of ascertainment of disease outcome applied to all participants, 

regardless of family history? 

 a) Yes 

 b) No 

 c) Unclear 

2. Was ascertainment of disease outcome completely blind to participants’ family history 

status? 

 a) Yes 

 b) No 

 c) Unclear 

3. Was the same method of ascertainment of family history applied to all participants? 

 a) Yes 

 b) No 

 c) Unclear 

4. Was ascertainment of family history status completely blind to disease outcome? 

 a) Yes 

 b) No 

 c) Unclear 

B-3
LONGITUDINAL DESIGNS ONLY 

5. Were participants with the disease outcome excluded at the start of the study? 

 a) Yes 

 b) No 

 c) Unclear 

 e) Not applicable (cross-sectional design) 

 

6. Was there adequate follow up of all participants? 

 a) at least 80% follow up 

 b) Less than 80% follow up, adequate description of those lost 

 c) Less than 80% follow up, inadequate or missing description of those lost 

 d) Unclear 

 e) Not applicable (cross-sectional design) 

 

CROSS-SECTIONAL DESIGNS ONLY 

7. Was the sampling method representative of the population intended to the study? 

 a) Yes (probability sampling) 

 b) No (non-probability sampling) 

 c) Unclear 

 e) Not applicable (longitudinal design) 

8. Was the participation rate adequate? 

 a) Yes, response rate at least 80% 

 b) Response rate less than 80%, adequate description of non-participants 

c) Response rate less than 80%, inadequate or missing description of nonparticipants 

 d) Unclear 

 e) Not applicable (longitudinal design) 

B-4
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

1) Was the spectrum of 

patients’ representative of the 

patients who will receive the 

test in practice? 

(Selection) 

We are interpreting this to be representative of the spectrum of 

patients seen within family practice or primary care, which should 

include all levels of severity or disease duration. The population 

would be representative of those seen in practice where the test 

is likely to be applied (primary care settings and providers). 

Note that this criterion speaks more to generalizability than to a true 

selection bias. 

We considered issues of generalisability in terms of a) demographic 

features (prevalence, age, gender, b) disease characteristics (severity 

and duration), and c) co-morbidities or differential diagnosis. Note 

method of recruitment and characteristics of those recruited. 

YES: Subjects represent spectrum of subjects seen within primary 

care settings. 

NO: Not that case control studies are considered by QUADAS to be a 

NO for this item, but we do not consider this to be a fatal flaw. 

Subjects that appear to represent a limited portion of the spectrum of 

patients with respect to disease severity, or duration, or risk for 

positive family history. Our review did not exclude studies that 

included subjects from specialty clinics or relatives of persons with 

the disease. As such, these relative may also be considered to be 

“high risk” for the disease (as the subjects 

patients may appear to be recruited because of high risk for family 

history and are scored NO. 

UNCLEAR: Description of participants is partial and there is 

uncertainty of the severity or duration of the disease. 

2) Were the selection criteria 

clearly described? 

(Selection) 

Look for a clear definition of the eligibility criteria (both inclusion and 

EXCLUSION criteria). 

Note the criteria used to select BOTH the proband/control and the 

relatives/ informants. 

YES: Appears that sufficient description of the eligibility criteria, the 

process of recruiting for both the probands/ informants and the 

relatives. 

NO: All relevant information for selection processes is not reported. 

The following information may be omitted or poorly described: 

a) how the probands/ informants were selected (possibly how 

the proxy informants were selected) 

b) how the relatives were selected 

UNCLEAR: Only partial information is reported and don’t feel you 

have enough information to score this item. 

B-5
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

3) Is the reference standard 

likely to correctly classify the 

target intervention? 

(Misclassification) 

The reference standard is the method used to determine the 

presence or absence of the target condition. The reference standard 

is therefore an important determinant of the diagnostic accuracy of a 

test. Estimates of test performance are based on the assumption that 

the index test is being compared to a reference standard which is 

100% sensitive and specific. 

Not applicable to this systematic review as we limited this review to 

including studies that used methods of the reference standard that we 

consider to correctly classify the target condition. 

4) Is the reference standard 

and index test short enough to 

be reasonably sure the target 

condition did not change 

between the two tests? 

(Misclassification) 

This problem may lead to misclassification bias as the disease may 

progress to a more advanced stage or there may be spontaneous 

recover. We do not anticipate that this is the context for family history, 

whereby the interval within which testing occurs will cause family 

history to be altered. 

Not applicable to this systematic review. 

B-6
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

5) Did the whole sample or a 

random selection of the 

sample receive verification 

using a reference standard of 

diagnosis? 

(Partial Verification bias) 

This item concerns to partial verification bias which occurs when 

not all of the study participants receive the reference standard (in our 

context, confirmation of the TRUE disease status). This is a form of 

selection bias. Sometimes the reason only a part of the sample 

receives the reference standard is because knowledge of the index 

test results influence the decision to perform the reference standard. 

Please note that in the context of family history, the reference 

standard can only be applied to the family members or relatives. The 

probands or informants are in essence the “index test” even though 

we are interested in the accuracy of the probands/ informants. 

 

We consider the whole sample to be ALL relatives for which the 

proband or informant provided information (including “Don’t know” 

status). 

YES: All relatives that the proband identifies/ reports upon represent 

the whole sample of relatives. As such, some form of verification is 

attempted for all identified relatives. 

NO: Not all relatives receive verification via the reference standard. 

As such, we consider partial verification bias to be present in the 

following situations: 

1) Knowledge of the index test will determine which relatives are 

reported to have the disease status. Often UNAFFECTED 

relatives do not have their disease status verified by any 

method (assume proband/informant report is the truth of the 

disease status); in this case, the disease status is verified in 

the AFFECTED relatives only. In this situation the outcomes 

of sensitivity and specificity cannot be computed. 

2) Relatives for which the proband/ informant indicates “Don’t 

know status” are excluded and do not have their disease 

status verified (no reference standard testing). 

3) Relatives that are DECEASED; as such they are excluded 

from having any verification undertaken (no reference 

standard testing). 

4) Relatives that are UNABLE TO PARTICIPATE in interviews 

or further clinical testing are excluded from having any 

verification method (no reference standard testing). 

UNCLEAR: Insufficient information to determine whether partial 

verification was present. 

B-7
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

B-8

6) Did the patients receive the 

same reference standard 

regardless of the index test? 

(Differential Verification Bias) 

“Differential verification bias occurs when some of the index test 

results are verified by a different reference standard. This is 

especially a problem if multimodal types of reference standards are 

used. For example, differential verification bias usually occurs when 

relatives who are testing positive (have the disease) based on the 

proband report “index test receive” a more invasive or extensive 

reference standard than those with a negative test result. 

In most accuracy studies evaluating the reporting of family history, 

there is the use of more than one method to verify the disease status 

of the relative and we have restricted these to interview with relative, 

medical record, disease or death registry, and contact with the 

subject physician. Using multi-modal approaches to verification of 

disease status seems to be necessary for this area of research; 

relatives may be deceased, live afar, or are incapacitated because of 

disease or frailty. It is expected that most studies will be unable to use 

a single reference standard method (for example interview with the 

relative) for all identified relatives. 

Verification can occur by different methods for different relatives or 

verification using multiple methods on the SAME relative (and a 

hierarchy of selection for disease status is used) [See Elbaz 20032

 In 

the latter case, some authors state decision rules at which of the 

multiple tests will be considered to reflect the truth of the disease 

status of the relative. In the area of mental health disorders, they will 

often consider “multiple informants” as the “reference” standard” and 

only include relatives for which there were “verification” reports from 

more than one informant. 

YES: All relatives received the SAME reference standard (for 

example, all living relatives were interviewed, and all deceased 

relatives had a proxy informant (for example interview with a spouse 

of the deceased relative). 

NO: All relatives did NOT receive the same references standard: 

1) This item can indicate that some of the relatives received a 

DIFFERENT reference standard. For example, consider the case 

where: 

 a) UNAFFECTED relatives have their disease status checked 

with medical records alone 

 rather than interview or disease or death registry 

 b) POSITIVE SCREEN relatives get a physical examination but 

those screening negative 

 do NOT get a physical examination. 

 c) DECEASED relatives have their disease status checked 

through medical records or 

 interviews of other relatives (rather than neurological exam 

received by living relatives). 

c) From all informants/relatives who were identified and 

provided some initial information, 

only those available for direct interview are provided with more 

extensive testing (for example with diagnostic mental health 

instruments); these relatives/ informants receive more extensive 

evaluation (i.e. different and additional reference standard tests). 

UNCLEAR: Some information provided but insufficient to determine 

this item. 
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

7) Was the reference standard 

independent of the index test 

(i.e. the index test did not form 

part of the reference 

standard)? 

(Incorporation bias) 

“When the result of the index test is used in establishing the final 

diagnosis, incorporation bias may occur. This incorporation will 

probably increase the amount of agreement between index test 

results and the outcome of the reference standard, and hence 

overestimate the various measures of diagnostic accuracy.” This item 

is not applicable in tests that do not use multiple tests as part of the 

reference standards. 

The index test in this systematic review is the reporting of family 

history by the probands or informants. There are some special 

situations where informants are unable to provide family history 

information (for example they are too ill); in these situations, proxy 

family members are asked to provide the family history. These same 

family members, who served as proxy informants, may also be asked 

about their own disease status and may have knowledge of the 

responses they gave on behalf of the informant. We view this as an 

issue of masking bias, not incorporation bias. 

In the mental health area, family history is often included as part of a 

list of criteria to determine the disease status of either the proband 

OR the relative. In addition to inquiring about family history, the 

verification of the disease is established by asking probands or 

relatives a checklist of symptoms or other questions related to 

establishing diagnostic criteria. Thus, in this situation, there is the 

potential for incorporation bias, as the knowledge of the family history 

OR details of the presence or absence of symptoms (provided by the 

informant or proband) may be used to establish the mental health 

disorder within the relative. 

In some studies evaluating probands with mental health disorders, 

the authors make it very clear that different instruments were used to 

collect family history from the probands and from the relatives. In this 

case, although family history is collected from both the 

proband/informant and the relative, we are assuming this is NOT 

incorporation bias. The response of the proband/ informant is 

independent and is not included in the information collected to 

establish disease within the relative. 

YES: The index test (proband/ informant) reporting of family history is 

NOT included in the determination of the disease status of the 

relatives. 

NO: The index test (proband/ informant) reporting of family history is 

included in the determination of the disease status of the relatives. 

UNCLEAR: Some information provided but insufficient to determine 

this item. 

B-9
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

8) Was the execution of the 

index test described in 

sufficient detail to permit 

replication of the test? 

(Incorporation bias) 

We are looking for sufficient detail for REPLICATION of the index 

test. This should include details of the “questions” used to probe 

family history, and if possible the degree of relative (for example 1DR, 

2DR, etc). Additionally, in studies evaluating probands with mental 

health disorders, note the sequence when family history was 

collected. We fully anticipate that there will be differences in the ways 

in which family history is collected across studies. If reported, 

evaluate the manner in which “don’t know” information was captured 

and classified. 

NB: We are aware that even if the method is replicable, it may not 

capture the quality of the manner in which FHx was captured; that is 

the study describes in detail the question used to probe family history, 

but the question is not well structured and may lead to poor or 

erroneous responses from the proband/informant. In this case, 

although the method was “replicable”, we do not evaluate this as NO 

for QUADAS; rather we comment on the nature of the question. 

YES: If the manner in which FHx was collected is well specified (for 

example, standardized questions, or instrument are detailed). 

NO: There is no information about the manner in which FHx was 

probed (for example the questions asked) or the methods used to 

collect the information (not clear if a standardized format was used). 

UNCLEAR: Indicate that a standardized instrument was used, but do 

not know what was probed. Partial information is provided but not 

enough to score this item. 

9) Was the execution of the 

reference standard described 

in sufficient detail to permit its 

replication? 

(Incorporation bias) 

In the case of the reference standard, we are looking for sufficient 

detail to be able to REPLICATE how disease status was established. 

In the case where interview of the relative is used as a reference 

standard, any additional probing (for example questions to establish 

presence of mental health disorder) should also be described. 

Note that in most studies multi-modal approaches were used to 

establish the disease status of the relative. As such it is important that 

the authors describe how 1) deceased versus living relatives had 

their disease status verified, 2) positive versus negative status 

relatives (based on index test) had their disease status verified, 3) 

relatives that were unable to be contacted or participate, and 4) 

relatives for which no additional information could be obtained. If 

reported evaluate how “don’t know” information was captured and 

classified. 

YES: Indicate the manner in which the disease status was 

established in relatives (self report, medical chart, linkage with 

registry, physical examination, etc). Note how missing information or 

“don’t know” (due to inability to get records for example) are handled. 

NO: The information is insufficient to replicate the reference standard. 

UNCLEAR: Indicate methods for some of the multiple sources used 

to verify the disease status within relatives but insufficient information 

to score this item. 

B-10
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

10) Were the index test results 

interpreted without knowledge 

of the results of the reference 

standard? 

(Blinding) 

We assume this bias to be associated with the collection of data from 

the researchers and is related to “review bias” or blinding. Family 

history collection from probands/ informants generally precedes 

contact with relatives for subsequent verification. As such the data 

collectors would typically not be aware of the true disease status of 

the relative when collecting family history from the informant. 

However, for some diseases, proxy informants (often relatives) are 

used when informants are incapacitated or deceased). In the context 

of this systematic review, bias can occur when the proxy members 

used to provide family history are also the relatives who are used to 

verify their own or others disease status. They are not blind to their 

previous report of the disease status of their own health or that of 

other relatives. 

YES: Index test results were interpreted without knowledge of the 

relatives’ disease status. If proxy informants (i.e. relatives) had their 

disease status verified by means other than interview (for example 

medical record linkage or clinical assessment), OR the proxy 

informants who are relatives were excluded from the pool of relatives 

in the analysis, then score YES for this item. 

NO: Index test are not interpreted without knowledge of the reference 

standard. Also, the potential for masking bias is likely, when the proxy 

informants (i.e. relatives) were used and then these SAME relatives 

were then asked to confirm their own or other relatives disease status 

by interview only. 

UNCLEAR: Partial description is provided but not enough information 

to score this item. 

B-11
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

11) Were the reference 

standard results interpreted

without knowledge of the index 

test? 

(Blinding) 

We assume this bias to be associated with the collection of data from 

the researchers and is related to “review bias” or blinding. Contact 

with the relatives is dependent on some minimal information or 

screening provided by the proband/informant. However, there is the 

possibility that the data collectors who contact the relatives (or 

check their medical records, etc.) are not blind to the report given by 

the proband/informant. Specifically, we look for a description 

specifying the masking of the data collectors of the reference 

standard. 

In the mental health area, data collectors ask relatives a series of 

screening questions to determine the presence of a mental health 

disorder. Subsequently, their responses to these questions are used 

by an EXTERNAL diagnostician to determine the status of the 

disease. Although, in some cases it is not clear if the data collector 

was blind to the report from the index test (proband/informant report), 

we do accept the external diagnostician as being blind in this case. 

YES: Study reports or methods describe blinding of data collectors or 

diagnostician verifying the disease status of the relative. 

NO: Study reports or methods confirm lack of blinding of the data 

collector to their disease status base don the informant report of 

family history. 

UNCLEAR: Blinding for some of the verification methods but not all 

of the methods is provided or there insufficient information to judge 

this item. 

12) Were the same clinical 

data available when test 

results were interpreted as 

would be available when the 

test is used in practice? 

(Misclassification) 

QUADAS instructions suggest that if the interpretation of the index 

test is fully automated and involves no interpretation then this item 

may not be relevant and can be omitted from the quality assessment 

tool. However, the interpretation of the family history collection (index 

test) may require some judgement and depends on what is asked of 

the proband/informant or relative. 

Clinical data in the context of family history collection in primary care, 

could refer to information from direct observation, or access to proxy 

informants (such as a 1DR who may accompany the proband). It is 

unlikely that a primary care physician may have access to medical 

records, disease registries and death registries with information about 

the status of the relatives. 

In the context of this systematic review, this item will not discriminate 

between studies; we will omit this item. 

B-12
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

13) Were un-interpretable/ 

intermediate test results 

reported? 

(Misclassification) 

In the context of family history collection it was difficult to define what 

results were “uninterpretable”. We assume that this item is interpreted 

to apply to disease status classification when the proband/informant 

(index test) did not know the disease status of the relative. Similarly, 

the disease status of the relative (reference standard) is not known or 

cannot be confirmed (for example, medical records may not have 

been easily obtained, or were inconclusive with regards to the 

disease status, or self report was unclear). 

In many studies (particularly mental health disorders) many of the 

relatives were excluded from the analysis and as such this is an issue 

of partial verification or a case of differential verification. 

In the context of this systematic review this item could not be 

disentangled from partial and differential verification bias and was not 

applicabled

B-13
Modified Quality Assessment of Diagnostic Accuracy Studies (OUADAS) 1

QUADAS ITEM 

(Topic/Bias) 

Interpretation for Family History OMAR Review 

14) Were withdrawals for the 

study explained? 

(Misclassification) 

“This occurs when subjects withdraw from the study before the 

results of either the index test or reference standard test are known. 

Note that the subjects considered in the context of the review include 

both the proband/informant sample AND the relatives/proxy sample. If 

patients differ systematically from those that remain in the analysis, 

then there is the potential for bias. 

We consider the sample of relatives to be those reported from the 

probands/ informants during the index test. As such, some studies do 

not specify the total sample of relatives reported; rather they report 

the number of relatives/ informants for which data was available. 

Potential subjects recruited can include those that are 1) alive, 2) 

deceased and a best proxy is found, 3) incapacitated to be 

interviewed and a best proxy is found, 

Potential recruited subjects are likely to be excluded if 1) they refuse 

to participate, or b) a proxy informant is not found. 

In some studies, subjects were further excluded if there was not a 

match 9 

YES: If all probands/ informants are accounted for in a flow diagram 

or reporting details; this includes the number of subjects as follows: 

1) those recruited 

2) providing consent or refusing consent 

3) for which a proxy respondent could not be provided 

4) unable to complete the family history collection (for example 

due to frailty) 

5) number not able to contact 

If all relatives (identified by the proband/ informants/ or registry) are 

accounted for in a flow diagram or reporting details; this includes the 

number of subjects as follows: 

1) ALL relatives identified by the probands/ informants/ registry 

2) relatives who gave consent or those refusing consent 

3) unable to complete family history 

4) for which a proxy informant could not be found 

5) who were deceased 

6) could not be contacted 

7) unable to get verification of disease status 

NO: If all informants who entered the study are not accounted for. 

UNCLEAR: Partial information is provided, but insufficient to judge 

this criteria. 

B-14
Modified QUADAS form 

REF ID# AUTHOR/ YEAR 

QUADAS ITEM RESPONSE COMMENTS 

1) Was the spectrum of patients’ representative of the 

patients who will receive the test in practice? 

YES 

NO 

UNCLEAR 

2) Were the selection criteria clearly described? YES 

NO 

UNCLEAR 

3) Is the reference standard likely to correctly classify 

the target intervention? 

YES 

NO 

UNCLEAR 

4) Is the reference standard and index test short 

enough to be reasonably sure the target condition did 

not change between the two tests? 

YES 

NO 

UNCLEAR 

5) Did the whole sample or a random selection of the 

sample receive verification using a reference 

standard of diagnosis? 

YES 

NO 

UNCLEAR 

6) Did the patients receive the same reference 

standard regardless of the index test? 

YES 

NO 

UNCLEAR 

7) Was the reference standard independent of the 

index test (i.e. the index test did not form part of the 

reference standard)? 

YES 

NO 

UNCLEAR 

8) Was the execution of the index test described in 

sufficient detail to permit replication of the test? 

YES 

NO 

UNCLEAR 

9. Was the execution of the reference standard 

described in sufficient detail to permit its replication? 

YES 

NO 

UNCLEAR 

10) Were the index test results interpreted without 

knowledge of the results of the reference standard? 

YES 

NO 

UNCLEAR 

11) Were the reference standard results interpreted 

without knowledge of the index test? 

YES 

NO 

UNCLEAR 

12) Were the same clinical data available when test 

results were interpreted as would be available when 

the test is used in practice? 

YES 

NO 

UNCLEAR 

13) Were uninterpretable/ intermediate test results 

reported? 

YES 

NO 

UNCLEAR 

14) Were withdrawals for the study explained? YES 

NO 

UNCLEAR 

B-15
B-16

References 

Elbaz A, McDonnell SK, Maraganore DM, et al. Validity 

of family history data on PD: evidence for a family 

information bias. Neurology 2003;61(1):11-7. 

 Whiting PF, Weswood ME, Rutjes AW, et al. Evaluation of 

QUADAS, a tool for the quality assessment of diagnostic 

accuracy studies. BMC Med Res Methodol 2006;6:9 
Webtable 1. General data for cancer studies 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Ahn 2008 

AlphaTocopherol, Beta-Carotene Cancer Prevention Study, cohort of Finnish male smokers 

prospective cohort 

19,652 male smokers 

and their 1DRs 

questionnaire histologically 

confirmed prostate cancer 

nar

Byeon 2007 

Seoul, Korea Asymptomatic adults aged 20 - 90 y 

prospective cohort 

860 all subjects questionnaire histologically 

confirmed colon or rectal cancer, adenoma≥10mm, 

villous adenoma, or adenoma with high grade dysplasia 

s

Cauley 2007 

women with osteoporosis, ≤80 y 

analysis of MORE and CORE RCTs 

2,576 all subjects 

followed for up to 8 y 

self-completion questionnaire 

incidence of breast cancer, histological confirmation 

sm

Cerhan 1996 

populationbased, Iowa, U.S. 

prospective cohort 

1,494 males aged 

67.9 ± 9.7 y 

questionnaire ICD oncology code 

61.9 

pthr

Chen 2008 

health professionals in U.S. 

cohort 51,525 age, clinical 

stage, Gleason score 

questionnaire histologically 

confirmed prostate cancer excluding stage T1a 

sth

Denic 2001 

married women who are United Arab Emirates nationals, ages 40 to 65 y 

crosssectional 1,445 women, ages 40 to 65 y interview physician- confirmed breast 

cancer 

sm

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; CORE=Continuing Outcomes Relevant to Evista; CRC=Colorectal cancer; FH9=International Classification of Diseases-Ninth Edition; MORE=Multiple Outcomes of Raloxifene Evaluation; n=number of subjects; PSA=prostate 

RCT=randomized controlled trial; y=years 

C-1
Webtable 1. General data for cancer studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Halapy 2005 

Ontario Breast Screening Program; women in Ontario 

retrospective cohort 

115,460 women aged 

50-69y with no personal history of breast cancer or augmentation mammoplasty, and free of acute breast symptoms 

interview histologically 

confirmed invasive breast cancer 

smr

Kalish 2000 

Massachusetts Male Aging Study mean age 54.1 ± 8.4 y 

prospective cohort 

1,149 all subjects questionnaire prostate cancer, 

not further specified

Prr

Kerlikowske 1997 

women accrued from a screening mammographic examination at the University of California San Francisco Mobile Mammography Screening Program 

crosssectional 39,542 women aged 30 y and older 

with no history of breast cancer and no previous mastectomies 

interview histologically 

confirmed invasive breast cancer 

smppd

Mäkinen 2002 

Finnish prostate cancer screening trial, Finland, men aged 55 to 67 y 

crosssectional 20,311 males aged 55 to 67 y questionnaire histologically confirmed prostate 

cancer 

P

C-2
Webtable 1. General data for cancer studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Rodriguez 1997 

male participants in U.S. Cancer Prevention Study II 

prospective cohort 

481,011 all subjects questionnaire ICD-9 code 185 

recorded as underlying cause of death 

binIn

Sandhu 2001 

East Anglian component of the European Prospective Investigation into Cancer, UK, men and women aged 45-74 y 

crosssectional 30,353 men and women aged 

40-79 y 40-49 y 50-59 y 60-69 y 70-79 y Women aged 40-79 y 40-49 y 50-59 y 60-69 y 70-79 y Men aged 40-79 y 40-49 y 50-59 y 60-69 y 70-79 y 

questionnaire registered in 

regional cancer registry with ICD-9 diagnosis codes 153.0-153.9, 154.0, 154.1 

r

Wei 2004 

patients from Nurses' Health Study and Health Professionals Followup Study 

combined prospective cohort 

134,365 women 

men 

questionnaire histologically 

confirmed colon or rectal cancer 

sthpIn

C-3
Webtable 2. Predictive values associated with FH definitions for breast cancer in longitudinal analyses 

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

C 

≥1 1DR female 

N N Cauley 2.5 12.5 0.05 0.98 

E 

≥1 1DR breast 

≥50 

OR 1 1DR ovarian 

N N Halapy 0.6 14.6 0.01 0.99 

E 

≥2 1DR breast and/or ovarian any age OR ≥1 1DR breast <50 y OR ≥1 1DR both breast and ovarian 

Y N Halapy 0.6 5.0 0.01 0.99 

Abbreviations: 1DR=first degree relative; FH=family history; FU=followup; mo=months; HR=hazard ratio; N=no; NPV=negative predictive value; P

RR=relative risk; y=years; Y=yes 

1 RR=relative risk, metric reported unless otherwise stated 

C-4
Webtable 3. Predictive values associated with FH definitions for breast cancer cross-sectional analyses 

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

C ≥1 1DR N N Denic 5.4 3.0 0.09 0.95 

Kerlikowske 0.7 9.9 0.01 0.99 

E consgs 

parents 

N N Denic 5.4 40.1 0.04 0.94 

Abbreviations: 1DR=first degree relative; consg=consanguineous; FH=family history; N=no; NPV=negative predictive value; NR=not reported; OR=predictive value; RR=relative risk 1 OR=odds ratio, metric reported unless otherwise stated 

C-5
Webtable 4. OR, HR and RR presented in each report for review question 1 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Ajlouni 2008 

diabetes (family history) 

diabetes OR 

(multivariate) 

3.09 2

prostate cancer (1DR family history) 

AhnJ prostate cancer age & trial intervention RR 1.91 12008 

prostate cancer (1DR family history) 

prostate cancer (advanced disease (stage

≥3) 

age & trial intervention RR 4.16 2

Alford 2004 

asthma (paternal history) 

asthma- current (seroatopy) 

sex of the study child, parental education, parental smoking, multiple pet ownership, firstborn status, and history of disease in other parent. 

OR 8.35 1

Annis 2005 

diabetes diabetes (1DR 

relative) 

NR crude 

odds ratio 

5 N

Bener asthma (father) asthma NR RR. 2.3 12005 asthma (mother) asthma NR RR. 2.1 1Bergmann 1997 

atopy dermatitis (father history) 

atopy - early adjusted OR 4.92 2

Bindraban 2008 

diabetes (1DR relative) 

diabetes NR OR 

(multi) 

2.7 1

diabetes type 2 (maternal) 

diabetes type 2 NR HR 2.65 1

diabetes type 2 (paternal) 

diabetes type 2 NR HR 1.79 0

Bjornholt 2000 

diabetes type 2 (both) diabetes type 2 NR HR 6.89 2

Abbreviations: 1DR=first degree relative; AMI=acute myocardial infarction; B=any family history; BMI=body mass index; BP=blood pressure; CI=co

CHD=coronary heart disease; CVD=cardiovascular disease; DBP=diastolic blood pressure; F=father’s side of family; FH=family history; HDL=high C=high density lipoprotein-cholesterol; HOMA-R=homeostasis model assessment; HR=hazard ratio, HRT=hormone replacement therapy; IGT=impaiLADA=latent autoimmune diabetes in adults; LDL=low density lipoprotein; MI=myocardial infarction; multi=multivariate; NGT=normal glucose tole

OR=odds ratio; POR=prevalence odds ratio; RR=relative risk; S=sibling; SBP=systolic blood pressure; SOB=shortness of breath; TG=triglycerides 

C-6
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Byeon 2007 

colorectal cancer (FH) 

proximal advanced neoplasm without polyps 

NR OR 6.0 1

Carlsson 2007 

diabetes(family) LADA 

Type2 Type1 

age, sex OR 3.92 

4.20 2.78 

231

Cauley 2007 

breast cancer (FH) breast cancer NR HR 2.83 1

prostate cancer prostate cancer 

(father or brother) 

age, alcohol intake, nutrients or food 

RR 3.7 1

prostate cancer prostate cancer 

(father 

age, alcohol intake, nutrients or food 

RR 2.3 0

Cerhan 1999 

prostate cancer prostate cancer 

(brother) 

age, alcohol intake, nutrients or food 

RR 6.5 2

Chen 2008 

prostate cancer (father & brother) 

prostate cancer ethnicity, BMI, total calories, 

vigorous activity, cigarette smoking, consumption of tomato sauce, calcium, alpha linolenic acid, fish, red meat 

RR 2.34 1

Chatkin 2003 

asthma or allergy (family history) 

current wheeze adjusted RR 1.85 1

Chatkin 2005 

asthma (FH) asthma smoking during pregnancy and 

confounding variables? 

RR 2.8 1

Denic 2001 

breast cancer breast cancer 

(consgs) 

none RR 0.66 0

C-7
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Djousse 2008 

MI (parental history) heart failure in 

male physician 

mutual adjustment for age (< 45, 45–49, 50–54, 55–59, 60–64, 65 + y), smoking (never, past, and current smokers), body mass index (< 25, 25–29, 30 + kg m–2), exercise (0, 

≤ 1, 2–4, 5 + per 

week), alcohol (< 1, 1–4, 5–7, and 8 + drinks/week), breakfast cereals (

≤ 1, 2–6, 7 + 

servings/week), cereal and history of hypertension, diabetes, left ventricular hypertrophy, atrial fibrillation, aspirin, fruit and vegetable consumption (< 3, 3–4, 5–6, 7–13, 14 + servings/week), and multivitamin use. 

HR 1.32 1

Dodani 2005 

coronary artery disease (FH) 

coronary artery disease 

NR OR 1.7 1

Ebbesson diabetes diabetes age and obesity OR 4.4 11998 diabetes glucose 

intolerance 

age and obesity OR 3.3 1

Garcia-Marcos 2005 

asthma (maternal & paternal) 

atopic wheezing male gender, mould stains, 

dog, cat 

OR 2.16 1

Gikas 2004 

diabetes (FH) diabetes age OR 6.91 5

C-8
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

allergic disease wheezing total number of people in the 

house, total number of rooms in the house, owning a pet, having a damp, musty smell, dampness or mold in the bedroom, having an open fireplace, maternal smoking, type of flooring in the bedroom 

Gillespie OR 1.67 12006 

allergic disease rash total number of people in the 

house, total number of rooms in the house, owning a pet, having a damp, musty smell, dampness or mold in the bedroom, having an open fireplace, maternal smoking, type of flooring in the bedroom 

OR 2.10 1

Granstrom 2008 

breast cancer (mother) 

breast cancer NR RR 1.75 1

Halapy 2005 

breast cancer (strong FH) 

breast cancer age, HRT, prior screen RR (rate 

ratio) 

2.14 0

Hariri 2006 

diabetes (FH) (moderate & high familial risk) 

diabetes all other demographic 

characteristic 

OR 3.6 2

Hariri 2006 

diabetes (high FH) diabetes demographic variables & BMI OR 4.6 1

Haron 2006 

diabetes (FH) diabetes NR OR 2.47 1

Hedlund 2006 

asthma symptom complex (FH) 

asthma socio economic class, 

occupational exposure to dust, gases or fumes, SOB 

OR 2.9 2

Hennis 2002 

diabetes (FH) diabetes adjusted (confounding 

variables) 

OR 2.85 2

Hilding diabetes (FH) diabetes in men age, BMI, physical activity OR 3.1 12006 diabetes (FH) diabetes in 

women 

age, BMI, physical activity OR 1.7 1 

C-9
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

MI MI age, population study of origin, 

cholesterol BMI, diabetes (women) 

Hippe RR 1.42 01999 

MI MI age, population study of origin, 

cholesterol BMI, diabetes (men) 

RR 1.30 1

diabetes (FH) diabetes (glucose 

tolerance) 

Jorgensen age, sex OR 2.46 12002 

diabetes (FH) diabetes & IGT age, sex OR 3.17 1

premature coronary heart disease (either parent) 

AMI age (men) RR 1.61 1

premature coronary heart disease (either parent) 

AMI age (women) RR 1.85 1

premature coronary heart disease (either parent) 

AMI age, study year, cardiovascular 

risk factors (men) 

RR 1.54 1

premature coronary heart disease (either parent) 

AMI age, study year, cardiovascular 

risk factors (women) 

RR 1.80 1

premature coronary heart disease (either parent) 

AMI age, study year, and 

cardiovascular risk factors, and socioeconomic indicators (men) 

RR 1.55 1

Jousilahti 1996 

premature coronary heart disease (either parent) 

AMI age, study year, and 

cardiovascular risk factors, and socioeconomic indicators (women) 

RR 1.80 1

stroke stroke (any type) age, study year, multifactorial 

double dagger adjustments 

RR (Men) 

Jousilahti 1.89 11997 

stroke stroke (any type) age, study year, multifactorial 

double dagger adjustments 

RR (women) 

1.80 1

Kadota 2008 

hypertension (FH) all stroke age, systolic BP, blood glucose, 

total cholesterol, smoking, drinking 

HR 1.36 0

Kalish 2000 

prostate cancer (F) prostate cancer (S) prostate cancer (B) 

prostate cancer age RR 2.59 

3.87 3.29 

111

C-10
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Kalyoncu 2001 

atopy (family) asthma 

current wheeze seasonal rhinitis 

NR POR 1.99 

2.18 2.20 

111

Kerlikowske 1997 

breast cancer (1DR relatives (mother, sister or daughter) 

ductal carcinoma In situ 

NR OR (30-

49 year old) 

2.4 1

Khan 2002 

NR NR NR NR NR N

Kim 2008 

diabetes (family history) 

diabetes NR RR 2.12 1

Krakowiak 2007 

atopy occupational 

asthma 

NR OR 5.9 1

Kulig  2000 

NR NR NR NR NR N

asthma (maternal history) 

Kurukulaaratc atopic wheeze NR OR 2.9 1hy 2004 asthma (paternal 

history) 

atopic wheeze NR OR 2.59 1

Lack 2003 

asthma (maternal) peanut allergy NR OR 1.55 0

Levitt 1999 

diabetes (Family history) 

diabetes NR RR (risk 

ratio) 

2.31 1

London 2001 

allergy and asthma combined (parental history) 

early-onset persistent asthma

NR RR 17.60 1

Lopez 1999 

NR NR NR NR NR N

Magno 2008 

MI (parental) CVD age, exercise, parental history, 

LDL, HDL, hypertension, microalbuminuria, adiponectin 

OR 2.81 1

prostate cancer (family history) 

prostate –specific antigen 

NR RR (rate 

ratio) 

1.3 0

prostate cancer (1DR relative(s)) 

prostate –specific antigen 

NR RR 1.26 0

Makinen 2002 

prostate cancer (father) 

prostate –specific antigen 

NR RR 1.18 0

C-11
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Meigs 2000 

diabetes type 2 (mother) diabetes type 2 (father) diabetes type 2 (both) 

diabetes type 2 age OR 3.4 

3.5 6.1 

222

Melbostad 1998 

asthma (parents or sibling) 

asthma (started in last 10 years) 

NR OR 3.1 2

Montnemery asthma asthma NR OR 3.71 32000 chronic bronchitis/ 

emphysema 

asthma NR OR 5.19 4

stroke subclinical stroke 

(cerebral infarct) 

age, gender, race, multiple stroke risk factors 

Morrison OR 1.64 12000 

stroke subclinical stroke 

(cerebral infarct) 

age, gender, race, OR 1.67 1

Motala 2008 

diabetes diabetes NR OR 3.5 -

Mohan 2003 

NR NR NR NR NR N

diabetes type 2 diabetes type 2 age, SBP, DBP, TG, HDL-c, 

NGT, IGT 

HR (women) 

1.86 1

diabetes type 2 diabetes type 2 age, SBP, DBP, TG, HDL-c, 

NGT, IGT, and BMI 

HR (women) 

1.84 1

diabetes type 2 diabetes type 2 age, SBP, DBP, TG, HDL-c, 

NGT, IGT, HOMA~R 

HR (women) 

1.81 1

Nakanishi 2003 

diabetes type 2 diabetes type 2 age, SBP, DBP, TG, HDL-c, 

NGT, IGT, BMI, and HOMA~R 

HR (women) 

1.79 1

Nyenwe 2003 

diabetes type 2 (FH) diabetes type 2 NR OR 9.45 3

Ones 1997 

asthma (1DR relatives) 

asthma NR OR 2.49 1

Ozdemir 2005 

diabetes (FH) diabetes NR OR 1.20 0

Park asthma (FH) asthma (Current) sex, race, education OR 3.3 21995 asthma (FH) asthma 

(physician reported) 

sex, race, education OR 3.1 2

Patrzalek 2003 

allergy (maternal/paternal) 

allergic disease NR OR 11.2 N

C-12
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Piros 2000 

MI (mother or father MI NR RR 2.45 1

Pohlabeln 2007 

NR NR NR NR NR N

Rahman 2008 

diabetes (parent & sibling) 

diabetes crude OR 3.30 1

Reinherz 2003 

psychiatric disorders (sibling) 

depression NR OR 

adjusted 

2.88 1

prostate cancer (≥1DR relatives) 

prostate cancer age at enrolment, race, years of 

e index, physical activity, intake of vegetables and fat, smoking status at study < vasectomy 

RR (rate ratio) 

Rodriguez 3.19 11997 

prostate cancer (FH) prostate cancer age at enrolment, race, years of 

e index, physical activity, intake of vegetables and fat, smoking status at study < vasectomy 

RR (rate ratio) 

1.60 1

colorectal cancer colorectal cancer age, smoking OR 

(women) 

2.77 1

colorectal cancer (one or more 1DR relatives) 

colorectal cancer age, smoking OR 

(women) 

2.11 1

Sandhu 2001 

colorectal cancer (two or more 1DR relatives) 

colorectal cancer age, smoking OR 

(women) 

5.29 1

Saquib 2005 

NR NR NR NR NR N

CHD (1DR relatives) CHD age, race, marital status, 

education, income, selfreported obesity, hypercholesterolemia, hypertension 

Scheuner OR 3.8 22006 

stroke (1DR relatives) stroke age, race, marital status, 

education, income, selfreported obesity, hypercholesterolemia, hypertension 

OR 1.5 1 

C-13
Webtable 4. OR, HR and RR presented in each report for review question 1 (continued) 

Author 

Year

Family 

history 

Outcome Confounder 

adjustment 

OR/HR 

/RR 

OR/HR 

/RR 

Sesso 2001 

MI (parental history maternal and/or parental) 

CVD, MI, stroke age, RR 

(women, MI) 

2.86 1

Shera 2007 

NR NR NR NR NR N

Sugimori 1998 

diabetes diabetes NR HR 1.65 1

C-14
Webtable 5. Quality items for cancer studies for review question 1 

Author Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Breast cancer Cauley 2006 

Yes Yes Yes Yes Yes At least 80% 

followup

Not applicable (longitudinal design)

Halapy 2005 

Yes Yes Unclear Yes Yes At least 80% 

followup

Not applicable (longitudinal design)

Denic 2001 

Unclear Unclear Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Unclear 

Kerlikowske 1997 

Yes Yes Unclear Yes Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling) 

C-15
Webtable 5. Quality items for cancer studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

CRC Byeon 2007 

Yes Unclear Yes Yes Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

No (nonprobability sampling) 

Sandhu 2001 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling) 

Wei 2004 

Yes Unclear Yes Unclear Yes Unclear Not 

applicable (longitudinal design) 

Prostate cancer Ahn 2008 

Yes Yes Yes Yes Yes Unclear Not 

applicable (longitudinal design)

Cerhan 1996 

Yes Yes No Yes Yes at least 80% 

followup 

Not applicable (longitudinal design)

Chen 2008 

Yes Unclear Yes Unclear Unclear Unclear Not 

applicable (longitudinal design)

C-16
Webtable 5. Quality items for cancer studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Kalish 2000 

Yes No Yes Yes Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Makinen 2002 

Yes Unclear Yes Yes Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Rodriguez 1997 

Yes Unclear Yes Yes Yes Unclear Not 

applicable (longitudinal design)

C-17
Webtable 6. Predictive values associated with FH definitions for colorectal cancer in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

Wei, M 1.31 8.51 0.021 0.992 

C ≥1 1DR N N 

Wei, F 1.01 7.91 0.021 0.992 

Abbreviations: 1DR=first degree relative; F=female; FH=family history; FU=followup; M=male; NPV=negative predictive value; N=No; PPV=positi

RR=relative risk 

1 RR=relative risk, metric reported unless otherwise stated 2 Colon and rectal cancer outcomes combined  3 Reported for males and females combined 

C-18
Webtable 7. Predictive values associated with FH definitions for colorectal cancer in cross-sectional analyses 

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

Sandhu, M&F 0.5 6.8 0.01 1.00 Byeon, M&F 4.5 12.7 0.07 0.96 Sandhu, M 0.6 6.1 0.01 0.99 Sandhu, F 0.4 7.4 0.01 1.00 Sandhu, M&F, premature(<50) 

0.0 5.1 0.00 1.00 

Sandhu, M&F, premature(<60) 

0.2 6.1 0.00 1.00 

Sandhu, M, premature (<60) 

0.3 5.6 0.00 1.00 

Sandhu M, premature (<50) 

0.0 4.2 0.00 1.00 

SandhuF, premature (<60) 

0.1 6.5 0.00 1.00 

C ≥1 1DR N N 

Sandhu, F, premature (<50) 

0.0 5.7 0.00 1.00 

C ≥2 1DR N N Sandhu, M&F 0.5 0.3 0.03 1.00 C ≥1 1DR, 

onset <65 

Y N Sandhu,M&F 0.5 2.4 0.02 1.00 

C ≥1 1DR, 

onset <45 

Y N SandhuM&F 0.5 0.3 0.02 1.00 

Abbreviations: 1DR=first degree relative; F=female; FH=family history; M=male; N=no; NPV=negative predictive value; NR=not reported; OR=odd

predictive value; Y=yes 

1 OR=odds ratio, metric reported unless otherwise stated 

C-19
Webtable 8. Predictive values associated with FH definitions for prostate cancer in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

B father N N Cerhan 6.5 3.0 0.13 0.94 B 

≥1 brother N N Cerhan 6.5 1.8 0.26 0.94 

B father and/or 

brother 

N N Chen 8.7 12.4 0.14 0.92 

Rodriguez 0.4 3.0 0.01 1.00 Ahn 5.7 3.0 0.11 0.95 

C 

≥1 1DR N N 

Cerhan 6.5 4.8 0.18 0.94 

C 

≥2 1DR N N Rodriguez 0.4 0.1 0.03 1.00 

Abbreviations: 1DR=first degree relative; FH=family history; FU=followup; NPV=negative predictive value; N=No; PPV=positive predictive value; R1 RR=relative risk, metric reported unless otherwise stated 

C-20
Webtable 9. Predictive values associated with FH definitions for prostate cancer in cross-sectional analyses 

FH category 

Specific definition 

age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

A any relative N N Kalish 5.0 9.6 0.14 0.96 B Father N N Makinen 2.4 3.5 0.03 0.98 B ≥1 brother N N Makinen 2.4 1.3 0.04 0.98 C ≥1 1DR N N Makinen 2.4 4.7 0.03 0.98 C ≥1 1DR, 

onset <60 

Y N Makinen 2.4 0.4 0.03 0.98 

D ≥1 1DR or 

2DR 

N N Makinen 2.4 7.7 0.03 0.98 

E paternal 

grandfather or ≥1 paternal uncle 

N Y Makinen 2.4 1.7 0.02 0.98 

E maternal 

grandfather or ≥1 maternal uncle 

N Y Makinen 2.4 1.8 0.03 0.98 

Abbreviations: 1DR=first degree relative; FH=family history; N=no; NPV=negative predictive value; NR=not reported; OR=odds ratio PPV=positive 1 OR=odds ratio, metric reported unless otherwise stated 

C-21
Webtable 10. General data for cardiovascular and stroke studies 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Djousse 2008 

association between parental history of MI & incident HF in PHS, U.S. 

RCT 20187 age questionnaire independently 

validated heart failure 

a

Dodani 2005 

Aga Khan University Hospital in Karachi, Pakistan recruited Pakistanis >18 y 

crosssectional study 

580 men and 

women >18 y; mean age of 46 y with 78.5% male 

questionnaire 

≥1 of documented myocardial infarction, angiographically confirmed coronary artery disease, or history of typical angina with positive treadmill test 

c

Hippe 1999 

Copenhagen Centre for Prospective Population Studies, men and women, age 20 to 93 y 

prospective cohort 

24,664 women 

men 

questionnaire ICD-8 code 410 s

dnd

Abbreviations: 1D=1DR; 1DR=first degree relative; 2DR=second degree relative; AMI=acute myocardial infarction; CAD=coronary artery disease; Cdisease; CVD=cardiovascular disease; FH=family history; FPG=fasting plasma glucose; HDL=high density lipoprotein; HF=heart failure; LDL=low dMI=myocardial infarction; MRI=magnetic resonance imaging; n=number of subjects; PHS=physician’s health study; RCT=Randomized Controlled S

attack; U.S.=United States of America; WHO=World Health Organization; y=years 

C-22
Webtable 10. General data for cardiovascular and stroke studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome H

a

Jousilahti 1997 

random sample of 25 to 64 y in Finland 

cohort 14,371 gender 

type of stroke 

questionnaire fatal or non-fatal 

stroke coded to ICD-8 432, 433, 436 or ICD-9 431, 432 

nnd

Jousilahti 1996 

Finland, males and females, 30 to 59 y 

prospective cohort 

15,620 (7,605 males, 8,015 females) 

Male Female 

questionnaire cause of death 

coded to ICD-8 410-414 or hospitalizations coded to ICD-8 410-411 

nnd

Kadota 2008 

cohort study of the National Survey on Circulatory Disorders, Japan 

longitudinal prospective cohort 

8,037 gender Survey, not 

further specified 

underlying cause of death coded to ICD-9 430-438, ICD-10 I60-I69 

n

Magno 2008 

community dwelling Filipino American women aged 40 to 86 y 

crosssectional 266 all subjects questionnaire hospitalization for CVD episodes or 

procedures OR ECG abnormalities (Minnesota codes 1.1, 1.2, 1.3, 4.1-4.4, 5.3 or 7.1.1), Rose angina, selfreport of physiciandiagnosed myocardial infarction 

c

C-23
Webtable 10. General data for cardiovascular and stroke studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome H

a

Morrison  2000 

the Atherosclerosis Risk in Communities Study, Houston, Texas, aged 45 to 64 y 

cohort 15,792 cerebral MRI 

on 1931 subjects 

≥55 

y 

interview clinical ischemic 

stroke not further specified 

rrd

Piros 2000 

railway engine drivers, Sweden, males aged 25-59 y 

prospective cohort 

1,409 males aged 

25 to 59 y 

Not specified, likely questionnaire 

hospital-diagnosed myocardial infarction with 

≥2 of 

typical chest pain, typical enzyme changes, ECG findings OR autopsy evidence OR sudden death with history of ischemic symptoms and no evidence for non-coronary death 

hnd

Scheuner 2006 

HealthStyles 2003 survey administered to American adults (male and female) with a mean age of 48.8 y 

crosssectional study 

3,956 stratified 

random sample of participants from 2003 survey 

questionnaire positive report of 

doctor-diagnosed CHD 

qr

Sesso 2001 

The Physician's Health Study (PHS) trial in the prevention of CVD and cancer 

prospective cohort study 

men n=20,515 Women n=37,985 

U.S. male physicians aged 40-84 y female health professionals aged 

≥45 y 

questionnaire events meeting 

WHO criteria for myocardial infarction, confirmed by independent committee 

a

C-24
Webtable 11. Predictive values associated with FH definitions for CHD in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

Djousse, M 5.1 31.1 0.06 0.69 Sesso, M 3.2 34.5 0.04 0.66 Hippe, M 9.0 19.3 0.11 0.81 Sesso, F 0.4 34.1 0.01 0.66 

B ≥1 parent N N 

Hippe, F 4.3 23.2 0.05 0.77 

Sesso, M 3.2 28.8 0.04 0.71 Piros, M 3.0 2.2 0.06 0.98 

B father N N 

Sesso, F 0.4 26.2 0.00 0.74 

Sesso, M 3.2 9.1 0.05 0.91 Piros, M 3.0 2.7 0.08 0.97 

B mother N N 

Sesso, F 0.4 12.3 0.01 0.88 

B both parents N N Sesso, M 3.2 3.5 0.05 0.97 

Sesso, F 0.4 4.4 0.01 0.96 

B ≥1 parent, 

onset <65y 

Y N Djousse, M 5.1 15.2 0.05 0.85 

Djousse, M 5.1 9.7 0.05 0.90 Jousilahti, M 

10.4 22.4 0.13 0.78 

B ≥1 parent, 

onset <60y 

Y N 

Jousilahti, F 

4.4 24.6 0.09 0.77 

B ≥1 parent, 

onset <55y 

Y N Djousse, M 5.1 5.7 0.05 0.94 

Jousilahti, M 

B father, onset 10.4 16.5 0.13 0.84 

<60y 

Y N 

Jousilahti, F 

3.2 17.4 0.03 0.83 

Abbreviations: 1DR=first degree relative; CHD=coronary heart disease; F=female; FH=family history; FU=followup; M=male; N=no; NPV=negative 

PPV=positive predictive value; RR=relative risk; y=years; Y=yes 

1 RR=relative risk, metric reported unless otherwise stated 2 Reference=no family history 

C-25
Webtable 11. Predictive values associated with FH definitions for CHD in longitudinal analyses (continued)

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

B mother, 

onset<60y 

Y N Jousilahti, 

M 

10.4 8.5 0.12 0.92 

Jousilahti, 

F 

3.2 10.4 0.05 0.90 

Jousilahti, M 

B both parents, 10.4 2.6 0.12 0.97 

onset <60y 

Y N 

Jousilahti, F 

3.2 3.1 0.03 0.97 

C-26
Webtable 12. Predictive values associated with FH definitions for CHD in cross-sectional analyses 

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

Nss

Scheuner, M&F premature 

B ≥1 parent N N 4.5 13.2 0.08 0

Magno, F 20.7 25.2 0.31 0

B father N N Scheuner, 

M&F, premature 

4.5 9.3 0.09 0

B mother N N Scheuner, 

M&F, premature 

4.5 6.3 0.10 0

B ≥1 sibling N N Scheuner, 

M&F, premature 

4.5 5.3 0.16 0

B both parents N N Scheuner, 

M&F, premature 

4.5 2.4 0.16 0

B ≥1 parent + ≥1 

sibling 

N N Scheuner, 

M&F, premature 

4.5 2.6 0.13 0

C ≥1 1DR N N Scheuner, 

M&F, premature 

4.5 38.8 0.08 0

C ≥2 1DR N N Scheuner, 

M&F, premature 

4.5 5.1 0.14 0

C ≥1 1DR, early 

onset 

Y N Scheuner, 

M&F, premature 

4.5 9.3 0.11 0

D ≥1 1DR + ≥1 

2DR, any age 

N N Scheuner, 

M&F, premature 

4.5 18.7 0.10 0

E fr, br, grfr<55, 

mr, sis, gmr<65 

Y N Dodani, M&F 19.1 49.5 0.23 0

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; br=brother; CHD=coronary heart disease; F=female; FH=family history; fr=fa

grmr=grandmother; M=male; mr=mother; N=no; NPV=negative predictive value; NR=not reported; OR=odds ratio; PPV=positive predictive value; s

C-27
Webtable 13. Quality items for CVD and stroke studies for review question 1 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

CVD Jousilahti 1996 

Yes Yes Yes Yes Yes At least 80% 

followup 

Not applicable (longitudinal design)

Sesso 2001 

Yes Unclear Yes Yes Yes Unclear Not 

applicable (longitudinal design)

Piros 2000 

Yes Unclear Unclear Unclear Unclear At least 80% 

followup 

Not applicable (longitudinal design)

Hippe 1999 

Yes Yes Yes Yes Yes Unclear Not 

applicable (longitudinal design)

Djousse 2008 

Yes Unclear Yes Yes Yes Unclear Not 

applicable (longitudinal design)

Abbreviations: 1DR=first degree relative; CHD=coronary heart disease; F=female; FH=family history; FU=followup; M=male; N=no; NPV=negative 

PPV=positive predictive value; RR=relative risk; y=years; Y=yes

C-28
Webtable 13. Quality items for CVD and stroke studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Magno 2008 

Yes No Yes No Not 

applicable (crosssectional design) 

Not applicable (crosssectional design) 

No (nonprobability sampling) 

Dodani 2005 

Yes No Unclear No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

No (nonprobability sampling) 

Scheuner 2006 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling) 

Stroke Morrison 2000 

Unclear Unclear Unclear Yes Yes Unclear Not 

applicable (longitudinal design)

Jousilahti 1997 

Yes Yes Yes Yes Yes Unclear Not 

applicable (longitudinal design)

Kadota 2008 

Yes Yes Yes Yes Yes At least 80% 

followup 

Not applicable (longitudinal design)

C-29
Webtable 14. Predictive values associated with FH definitions for stroke in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion Studies

Disease prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

Morrison 1.9 29.1 0.02 0.98 Jousilahti, M, premature disease 

3.4 4.9 0.07 0.97 

Kadota, M 3.9 20.4 0.03 0.96 Jousilahti, F, premature disease 

2.6 6.2 0.06 0.98 

B 

≥1 parent N N 

Kadota, F 2.7 20.7 0.03 0.97 

Jousilahti, M, premature disease 

B father N N 3.4 2.1 0.08 0.97 

Jousilahti, F, premature disease 

2.6 2.8 0.06 0.98 

Jousilahti, M, premature disease 

B mother N N 3.4 2.6 0.07 0.97 

Jousilahti, F, premature disease 

2.6 3.2 0.06 0.98 

Abbreviations: 1DR=first degree relative; F=female; FH=family history; FU=followup; M=male; N=no; NPV=negative predictive value; PPV=positiv

RR=relative risk; y=years 

1 RR=relative risk, metric reported unless otherwise stated 

C-30
C-31

Webtable 15. General data for diabetes studies 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Ajlouni 2008 

study of diabetes and performance risk score in Hindustani Surinamese, African Surinamese, and Dutch aged 35-60, Amsterdam Netherland 

crosssectional 1,415 age interview clinical evaluation c

Annis 2005 

National Health and Nutrition Examination Survey (NHANES) of the civilian, not institutionalized U.S. population over the age of 20 y 

retrospective cohort 

10,283 10,067 analysed 

men and women 320y 

interview self-report of 

physician diagnosis 

s

Bindraban 2008 

study of Jordanian aged 25 y and above, Jordan 

crosssectional 1,121 Gender, age interview fasting glucose>7.0mmol/l 

or self-reported diabetes 

c

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; DM=diabetes mellitus; EPIC=European prospective investigation of cancer; F

FPG=fasting plasma glucose; GTT=glucose tolerance test; LPG=level of plasma glucose; n=number of subjects; OGTT=oral glucose tolerance test; W

Organization; y=years 
Webtable 15. General data for diabetes studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Bjornholt 2000 

accruement from a cardiovascular screening survey in Oslo, Norway 

prospective followup study 

1,947 healthy nondiabetic men 

aged 40 to 59 years with fasting blood glucose levels <110 mg/dl at baseline 

questionnaire diabetes confirmed 

from ≥2 of: fasting glucose≥120 mg/dl/2-h glucose ≥180mg/dl OR hospital diagnosis of diabetes OR death coded to ICD-9 diabetes codes 

c

Boer 1996 

Zutphen Elderly Study - a longitudinal study on the risk factors for chronic diseases 

crosssectional study 

468 men aged 69 

to 90 y 

interview fasting 

glucose≥7.8mmol/l OR 2-h glucose ≥11.1mmol/l or known diabetes 

c

Carlsson 2007 

Nord-Trøndelag Health Study, Norway 

crosssectional study 

64,498 men and 

women >20 y 

questionnaire incompletely 

described but likely self-report of physician diagnosis 

c

Ebbesson 1998 

residents of Alaska, U.S. men and women aged ≥25 y 

prospective cohort 

391 men and 

women aged ≥25 y women only men only 

interview fasting glucose≥7.8 

mmol/l or WHO 1985 criteria 

c

Gikas 2004 

Salamis, Greece, age 20-94y 

crosssectional 2,805 all subjects interview self-report of doctor diagnosis of 

diabetes or hypoglycemic therapy 

s

C-32
Webtable 15. General data for diabetes studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Hariri 2006 

National Health and Nutrition Examination Survey, United States population, males and non-pregnant females ≥20 y 

cohort study 

3,823 non-pregnant 

adults, ≥20 y 

interview self-report of 

physician diagnosis OR fasting glucose ≥126mg/dl 

se

Hariri 2006 

HealthStyles 2004 mail survey of health-related attitudes and beliefs 

crosssectional study 

4,345 U.S. adult 

population, aged 18 and over 

questionnaire self-report of 

physician diagnosis of diabetes 

s

Haron 2006 

Northern Israeli Circassian men and women, aged 35 y and older 

retrospective cohort 

740 men and 

women >35y 

interview hypoglycemic 

therapy OR fasting glucose ≥126mg/dl 

on two occasions OR 2-hr glucose ≥200mg/dl 

c

Hilding 2006 

Stockholm Diabetes Prevention Programme, men and women aged 35 to 56 y from the outskirts of Stockholm 

crosssectional study 

7,949 total 3,128 men and 4,821 women

men and women, aged 35-56y, half with a FH of diabetes 

questionnaire WHO 1998 criteria c

Meigs 2000 

Framingham Offspring Study aged 12 to 58 y at baseline 

cohort 2,527 all subjects Original clinical 

evaluation data from first generation of parent-offspring cohort study 

fasting glucose≥7.8mmol/l or self-report of hypoglycemic therapy 

c

C-33
Webtable 15. General data for diabetes studies (continued)

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Mohan 2003 

Chennai Urban Population Study, Chennai, India, men and women aged >= 20 

prospective cohort 

1,262 men and 

women aged >= 20 y 

interview hypoglycemic 

therapy OR fasting glucose ≥126mg/dl 

OR 2-hr glucose ≥200mg/dl 

c

Nakanishi 2003 

JapaneseAmericans, Hawaii and Los Angeles, CA, U.S. 

prospective Cohort 

403 men 557 women 

men aged 61.2±1.9 y (FH+); 67.2±1.0 y (FH-) women aged 60.7±1.4 y (FH+); 61.9±0.8 y (FH-) 

survey, not further specified 

1998 WHO criteria for diabetes on basis of oral GTT 

 c

Nyenwe 2003 

Nigeria, age >40y crosssectional 491 all subjects questionnaire WHO 1999 criteria or self-report of 

physician diagnosis 

c

Rahman 2008 

European Prospective Investigation (EPIC) of Cancer-Norfolk, age 40 to 79 y 

prospective cohort 

24,495 all subjects questionnaire incompletely 

described but likely physician diagnosis OR receiving hypogycemic therapy OR elevated nonfasting glucode OR elevated HBA1c 

shpdhp

Shera 2007 

random sample of subjects >24 y in Pakistan 

crosssectional 5,433 gender unclear fasting glucose >140 mg/dl or 2 h 

glucose >200 mg/dl 

c

C-34
Webtable 16. Predictive values associated with FH definitions for diabetes in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

B 

≥1 parent N N Meigs, M&F 8.7 23.7 0.17 0.94 

Bjornholt, M 7.3 10.6 0.15 0.94 

B father N N Meigs, M&F 8.7 13.2 0.16 0.92 

Bjornholt,M 7.3 3.9 0.13 0.93 

B mother N N Meigs, M&F 8.7 12.1 0.20 0.93 

Bjornholt, M 7.3 7.2 0.16 0.93 

B both Meigs, M&F 8.7 1.7 0.26 0.92 

parents 

N N 

Bjornholt,M 7.3 0.5 0.30 0.93 

Boer, M 16.2 9.3 0.38 0.86 Nakanishi, M 14.4 15.1 0.20 0.87 

C 

≥1 1DR N N 

Nakanishi, F 12.2 16.3 0.21 0.89 

C 

≥1 parent or sibling 

N N Rahman, 

M&F 

1.3 12.2 0.02 0.99 

C 

≥1 parent and 

≥1 

sibling 

N N Rahman, 

M&F 

1.3 0.8 0.04 0.99 

Abbreviations: 1DR=first degree relative; FH=family history; FU=followup; N=no; NPV=negative predictive value; NR=not reported; PPV=positive 

risk; y=years 

1 RR=relative risk, metric reported unless otherwise stated 2 Male and female data combined 

C-35
Webtable 17. Predictive values associated with FH definitions for diabetes in cross-sectional analyses 

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

Nyenwe, M&F 

6.9 7.7 0.26 0.95 

Annis, M&F 9.6 24.1 0.19 0.93 Carlsson, M&F 

2.1 10.4 0.05 0.98 

B ≥1 parent N N 

Mohan, M&F 12.0 19.7 0.18 0.89 

B father N N Annis, M&F 9.6 10.4 0.17 0.91 

Carlsson, M&F 

2.1 4.3 0.04 0.98 

B mother N N Annis, M&F 9.6 16.2 0.22 0.93 

Carlsson, M&F 

2.1 6.6 0.06 0.98 

B ≥1 sibling N N Annis, M&F 9.6 13.1 0.28 0.93 

Carlsson, M&F 

2.1 3.1 0.08 0.98 

B brother N N Annis, M&F 9.6 7.5 0.30 0.92 

Carlsson, M&F 

2.1 2.5 0.10 0.98 

B sister N N Annis, M&F 9.6 8.2 0.31 0.92 

Carlsson, M&F 

2.1 2.2 0.10 0.98 

B ≥1 child N N Carlsson, 

M&F 

2.1 0.8 0.06 0.98 

B father or 

brother 

N N Carlsson, 

M&F 

2.1 5.7 0.05 0.98 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; FH=family history; N=no; NPV=negative predictive value; NR=not reported; 

value; RR=relative risk; y=years; Y=yes 

1 OR=odds ratio, metric reported unless otherwise stated 2Type 2 diabetes 3Data for males and females combined

C-36
Webtable 17. Predictive values associated with FH definitions for diabetes in cross-sectional analyses (continued)

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

B mother or 

sister 

N N Carlsson, 

M&F 

2.1 7.5 0.06 0.98 

Carlsson, M&F 

2.1 15.2 0.06 0.99 

Bindraban, M&F 

13.7 59.9 0.19 0.94 

Shera, M 9.3 11.0 0.22 0.92 

C ≥1 1DR N N 

Shera, F 8.4 10.3 0.18 0.93 

Gikas, M&F 8.7 23.3 0.24 0.96 Annis, M&F 9.6 31.5 0.19 0.95 Haron, M 14.9 27.0 0.18 0.86 

C ≥1 parent 

or sibling 

N N 

Haron, F 10.6 29.9 0.14 0.91 

C ≥2 1DR N N Carlsson, 

M&F 

2.1 1.9 0.13 0.98 

C ≥2 1DR 

(parents or sibling) 

N N Annis, M&F 9.6 8.2 0.32 0.92 

C ≥3 1DR 

(parents or sibling) 

N N Annis, M&F 9.6 2.2 0.52 0.91 

Ebbesson, M&F 

6.2 19.0 0.12 0.95 

Ebbesson, M 4.2 15.4 0.09 0.97 

D ≥1 1DR, 

aunt or uncle 

N N 

Ebbesson, F 8.8 20.0 0.17 0.93 

D ≥1 1DR or 

≥1 2DR 

N N Ajlouni, M&F 17.4 43.4 0.23 0.87 

D ≥1 1DR or Hilding, M 2.3 50.1 0.04 0.99 

≥2 2DR 

N N 

Hilding, F 1.4 52.7 0.02 0.99 

C-37
Webtable 17. Predictive values associated with FH definitions for diabetes in cross-sectional analyses (continued)

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

E ≥1 1DR 

and 1 2DR, same lineage OR 1 1DR OR both parents OR 2 2DR, same lineage 

N Y Hariri, M&F 10.4 35.8 0.21 0.96 

E ≥2 1DR, 

same lineage OR ≥11DR and ≥2 2DR, same lineage OR ≥3 2DR same lineage 

N Y Hariri, M&F 10.4 16.4 0.29 0.93 

C-38
Webtable 18. Quality items for diabetes studies for review question 1 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Diabetes Bjornholt 2000 

Yes Yes Yes Yes Yes At least 80% 

followup 

Not applicable (longitudinal design) 

Mohan 2003 

Yes No Unclear No Not 

applicable (crosssectional design) 

Not applicable (crosssectional design) 

Yes (probability sampling) 

Rahman 2008 

Yes No Yes Yes Yes At least 80% 

followup 

Not applicable (longitudinal design)

Sugimori 1998 

Yes Yes Unclear Yes Yes Unclear Not 

applicable (longitudinal design)

Meigs 2000 

Yes Unclear Yes Yes Yes At least 80% 

followup 

Not applicable (longitudinal design)

C-39
Webtable 18. Quality items for diabetes studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Shera 2006 

Yes Unclear Unclear Unclear Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Bindraban 2008 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Ajlouni 2008 

Yes No Unclear No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Boer 1996 

Yes Unclear Yes Yes Yes Less than 

80% followup, inadequate or missing description of those lost 

Not applicable (longitudinal design)

Nakanishi 2003 

Yes Yes Unclear Yes Yes Unclear Not 

applicable (longitudinal design)

C-40
Webtable 18. Quality items for diabetes studies for review question 1 (continued)

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Hariri 2006 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Haron 2006 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Gikas 2004 

Yes No Unclear No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

No (nonprobability sampling) 

Hilding 2006 

Yes Yes Yes Yes Not 

applicable (cross sectional design) 

Not applicable (crosssectional design) 

Unclear 

Nyenwe 2003 

Yes No Unclear No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

C-41
Webtable 18. Quality items for diabetes studies for review question 1 (continued)

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Carlsson 2007 

Unclear Unclear Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Ebbesson 1998 

Yes No Unclear No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Annis 2005 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Hariri 2006 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

C-42
Webtable 19. General data for asthma studies 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Alford 2004 

relationship between parental onset and duration of disease and the risk of paediatric atopic disease in children from birth to 6/7 y old, U.S. 

835 childhood 

and adulthood 

maternal interview 

asthma: self-report symptoms within previous 12 mo and currently using asthma medication Atopy: positive skin prick test 

ppa

Bener 2005 

government primary schools in the State of Qatar 

crosssectional study 

3,204 school 

children living in urban and semi-urban areas, 51.9% boys and 48.1% girls, with a mean age of 8.92 y 

parental interview ISAAC criteria for 

self-report of physician diagnosis of asthma OR asthma treatment OR hospital admission 

p

Bergmann 1997 

evaluation of parental history and cord bloodIgE for the appropriate atopic phenotypes in the infants in 6 German obstetric department, Germany 

cohort 1,314 gender, cord 

blood IgE, family history (father, mother) 

parental questionnaire 

self-report of physician diagnosis of atopic disease OR diagnosis on basis of research clinical examination or reported symptomatology OR computer algorithm diagnosis on basis of specific criteria for symptomatology and clinical signs 

qina

Abbreviations: 1DR=first degree relative; FH=family history; IgE=immunoglobin E; ISAAC=international study of asthma and allergies in childhood

y=years; U.S.=United States of America 

C-43
Webtable 19. General data for asthma studies (continued) 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Chatkin 2003 

children age 4 to 5 y in Brazil 

cohort 981 all subjects maternal 

interview 

ISAAC criteria for current asthma 

p

Chatkin 2005 

male and female children age 6 to 7 y in southern Brazil 

crosssectional 494 all subjects maternal interview ISAAC criteria for current asthma p

GarciaMarcos 2005 

evaluation of environmental and family risk factors for atopic and non-atopic wheezing among school children 9-12 y of age (ISAAC phase II), Spain 

crosssectional 2720 atopic and non-atopic 

wheezing 

questionnaire ISAAC criteria for 

current wheezing 

p

Hu 1995 

Los Angeles & San Diego California young adults ages 20 to 22 y 

cross sectional 

2,041 all subjects questionnaire physician-reported 

asthma plus one of: asthma medication in previous 12 months or coughing, wheezing, shortness of breath lasting >3 days in previous 12 months 

sq

C-44
Webtable 19. General data for asthma studies (continued) 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

London 2001 

a schoolbased study of Southern California children 

crosssectional 5,046 presence of a sibling, 

maternal smoking 

parents or guardians completed a selfadministered questionnaire during the school year 

 “yes” response to the question, has a doctor ever diagnosed this child as having asthma? 

pcaqd

Lopez 1999 

study of genetic and environmental influences on atopic immune response in term neonates born in women’s health care center, Brazil 

cohort 114 sex, ethnicity maternal 

questionnaire 

atopic dermatitis according to criteria of Hanifin & Rajka OR wheezing on at least 2 occasions with good response to beta agonist OR history of immediate urticaria, vomiting, diarrhea and or wheezing in response to specific food at least twice. Single manifestations of symptoms indicating probable disease included 

ppa

Melbostad 1998 

Norway, farmers and spouses 

crosssectional 8,482 all subjects Never/ever 

smoker animal production/no animal production 

questionnaire unclear 

data analyzed for ''current asthma' 

sqs

C-45
Webtable 19. General data for asthma studies (continued) 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Montnemery 2000 

study of familial related riskfactors in the development of chronic bronchitis/emphysema in 20-59 y old population Sweden 

crosssectional 12073 age, gender questionnaire positive response to question, 'have 

you now, or have you had asthma?' 

s

Õneş1997 

Istanbul, Turkey schoolchildren aged 6 to 12 y 

crosssectional 2,216 six randomly selected 

primary schools 

parental questionnaire 

ISAAC criteria for self-report of physician diagnosis of asthma 

p

Patrzalek 2003 

children age 0 to 3 y, Warsaw, Poland 

prospective cohort 

141 all subjects parental 

questionnaire 

atopic dermatitis OR recurrent wheeze OR food allergy, not further defined 

pcIg

Pohlabeln 2007 

relationship between pet ownership at time of birth and prevalence of atopic diseases approximately 2 years later in 5 hospitals in three cities. Germany 

Cohort 3,132 sex, parental 

education, study center, family history (maternal & paternal, sibling) 

maternal questionnaire 

ISAAC criteria for atopic disease 

p

C-46
Webtable 19. General data for asthma studies (continued) 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Sugiyama 2002 

Japanese schoolchildren, 13 to 14 y, part of International Study of Asthma and Allergies in Childhood, Phase One 

crosssectional 4,466 all subjects with complete 

data 

questionnaire ISAAC criteria for 

mild, moderate or severe wheezing 

sq

C-47
Webtable 19. General data for asthma studies (continued) 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Tariq 1998 

babies born on the Isle of Wight 

prospective cohort 

1,218 infants at 

ages 1, 2, and 4 y 

interview asthma: ≥3 

episodes of wheeze, each lasting ≥3 days; 

Atopy: ≥3 separate episodes of wheeze, each lasting at least 3 days or recurrent, scaly, pruritic, erythematous rash in typical distribution lasting >6 weeks OR two of thee nasal symptoms (discharge, blockage, recurrent sneezing) accompanied by eye symptoms OR skin rasj or respiratory or abdominal symptoms within 4 hours of ingestion of particular food on 2 occasions 

ps

C-48
Webtable 20. Predictive values associated with FH definitions for atopic disease in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

B atopy, both 

parents 

N N Bergmann 

M&F, onset ≤2y 

0.4 NA 0.25 0.84 

Tariq, M&F, onset ≤4y 

B atopy, father N N 26.8 25.5 0.29 0.74 

Pohlabeln onset

≤2y 

23.0 19.8 0.27 0.78 

Tariq, M&F onset 

≤4y 

B atopy, mother N N 26.8 33.7 0.29 0.74 

Pohlabeln onset

≤2y 

23.0 23.4 0.29 0.79 

Tariq, M&F, onset 

≤4y 

B atopy, 

≥1 27.3 36.9 0.34 0.76 

sibling 

N N 

Pohlabeln onset

≤2y 

23.0 10.6 0.33 0.78 

Tariq, M&F, onset 

≤4y 

C atopy, 

≥1 26.8 58.5 0.29 0.77 

1DR 

N N 

Pohlabeln onset

≤2y 

23.0 43.1 0.28 0.81 

D atopy, 

≥1 of 

parents, siblings, grandparents 

N N Lopez, 

onset 

≤1y 

38.6 53.5 0.46 0.70 

Abbreviations: 1DR=first degree relative; FH=family history; FU=followup; N=no; NPV=negative predictive value; NR=not reported; PPV=positive 

risk; y=years 

1 RR=relative risk, metric reported unless otherwise stated 

C-49
Webtable 21. Predictive values associated with FH definitions for atopic disease cross-sectional analyses 

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV fostudy sample 

B atopy, 

≥1 

parent 

N N Patrzalek, 

M&F, 

≤13y 

36.2 22.0 0.52 0.68 

B atopy, 

father 

N N Alford, M&F, 

onset 6-7y 

30.5 37.2 0.38 0.74 

B atopy, 

father, childhood 

Y N Alford, M&F, 

onset 6-7y 

30.5 22.6 0.40 0.72 

B atopy, 

mother 

N N Alford, M&F, 

onset 6-7y 

30.9 45.5 0.33 0.71 

B atopy, 

mother, childhood 

Y N Alford, M&F, 

onset 6-7y 

30.9 25.4 0.28 0.68 

Abbreviations: 1DR=first degree relative; F=female; FH=family history; FU=followup; M=male; N=no; NPV=negative predictive value; OR=odds ra

value; y=years; Y=yes 

1 OR=odds ratio, metric reported unless otherwise stated 

C-50
Webtable 22. Predictive values associated with FH definitions for asthma in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV for study sample

B asthma, 

mother 

N N Tariq, 

M&F, onset ≤4y 

14.9 10.4 0.25 0.86 

B atopy, mother N N Tariq, 

M&F, onset ≤4y 

14.8 33.7 0.18 0.87 

C atopy, 

≥1 

sibling 

N N Tariq, 

M&F, onset ≤4y 

15.9 36.9 0.21 0.87 

C atopy, 

≥1 

1DR 

N N Tariq, 

M&F, onset ≤4y 

14.8 58.5 0.17 0.89 

Abbreviations: FH=family history; FU=followup; N=no; NPV=negative predictive value; PPV=positive predictive value; RR=relative risk; y=years 1 RR = relative risk, metric reported unless otherwise stated 

C-51
Webtable 23. Predictive values associated with FH definitions for asthma in cross-sectional analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

B asthma, ≥1 

parent 

N N London, 

M&F, onset 9-16y 

14.4 18.8 0.30 0.89 

London, M&F, onset 9-16y 

14.4 8.6 0.32 0.87 

GarciaMarcos, M&F, onset 9-12y 

13.1 5.4 0.22 0.87 

Bener, M&F, onset 6-12y 

19.8 9.0 0.40 0.82 

B asthma, 

father 

N N 

Alford, M&F, onset 6-7y 

6.9 8.0 0.18 0.94 

B asthma, 

father, childhood 

Y N Alford, M&F, 

onset 6-7y 

6.9 5.7 0.19 0.94 

Abbreviations: 1DR=first degree relative; F=female; FH=family history; N=no; NPV=negative predictive value; M=male; mod=moderate; NR=not rePPV=positive predictive value; sev=severe; y=years; Y=yes 1 OR=odds ratio, metric reported unless otherwise stated 

C-52
Webtable 23. Predictive values associated with FH definitions for asthma in cross-sectional analyses (continued)

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

London, M&F, onset 9-16y 

14.4 11.3 0.29 0.87 

GarciaMarcos, M&F, onset 9-12y 

13.1 8.6 0.20 0.88 

Bener, M&F, onset 6-12y 

19.8 11.8 0.37 0.82 

B asthma, 

mother 

N N 

Alford, M&F, onset 6-7y 

7.1 13.6 0.08 0.93 

B asthma, 

mother, childhood 

Y N Alford, M&F, 

onset 6-7y 

7.1 7.8 0.08 0.93 

B asthma, ≥1 

sibling 

N N Bener, M&F, 

onset 6-12y 

19.8 36.5 0.34 0.89 

B asthma, 

both parents 

N N London, 

M&F, onset 9-16y 

14.4 1.1 0.51 0.86 

B ≥1 parent 

or sibling 

N N Melbostad, 

M&F 

3.1 12.5 0.07 0.98 

C-53
Webtable 23. Predictive values associated with FH definitions for asthma in cross-sectional analyses (continued)

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV for study sample 

Montnemery, M&F 

5.5 17.3 0.13 0.96 

Hu, M&F, onset ≤20y 

8.2 21.9 0.17 0.94 

Hu, M&F, onset ≤20y 

11.8 21.9 0.24 0.91 

Ones, M&F, onset 6-12y 

9.8 7.8 0.20 0.91 

Chatkin, M&F, onset ≤6y 

12.8 51.8 0.19 0.94 

C asthma, ≥1 

1DR 

N N 

Chatkin, M&F, onset ≤4y 

18.3 56.8 0.22 0.87 

D asthma, ≥1 

1DR or grandparent 

N N Sugiyama, 

M&F, onset 13-14y 

7.7 19.0 0.16 0.94 

C-54
Webtable 24. Quality items for asthma and atopy studies for review question 1 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Asthma & atopy Tariq 1998 

Yes No Yes Yes Yes At least 80% 

followup 

Not applicable (longitudinal design) 

Hu 1997 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (crosssectional design) 

Unclear 

Melbostad 1998 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

C-55
Webtable 24. Quality items for asthma and atopy studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representatve sampling (crosssectional) (selection bias) 

Montnemery 2001 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

London 2001 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Unclear 

Chatkin 2003 

Yes Unclear Yes Unclear Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Chatkin 2005 

Yes Yes Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Sugiyama 2002 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

C-56
Webtable 24. Quality items for asthma and atopy studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representatve sampling (crosssectional) (selection bias) 

Ones 1997 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling)

Bener  2005 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (cross sectional design) 

Yes (probability sampling) 

GarciaMarcos 2005 

Yes No Yes No Not 

applicable (cross sectional design) 

Not applicable (crosssectional design) 

Yes (probability sampling) 

Lopez 1999 

Yes Unclear Unclear Yes Yes at least 

80% followup 

Not applicable (longitudinal design) 

Pohlabeln 2007 

Yes Unclear Yes Yes Yes Less than 

80% followup, inadequate or missing description of those lost 

Not applicable (longitudinal design) 

C-57
Webtable 24. Quality items for asthma and atopy studies for review question 1 (continued) 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representatve sampling (crosssectional) (selection bias) 

Alford 2004 

Yes No Yes No Not 

applicable (crosssectional design) 

Not applicable (crosssectional design) 

Yes (probability sampling) 

Bergmann 1997 

Yes Unclear Unclear Yes Yes Unclear Not 

applicable (longitudinal design) 

Patrzalek 2003 

Unclear Unclear Yes No Not 

applicable (crosssectional design) 

Not applicable (crosssectional design) 

Yes (probability sampling) 

C-58
C-59

Webtable 25. General data for mental health studies 

Author 

Year 

Study 

setting 

Study 

design n Sub-groups measured How/when FH obtained Definition of outcome 

Reinherz 2003 

predominately Caucasian, working-class community in the north eastern U.S., men and women's life course of a single age (5-26 y) 

prospective cohort 

354 men and 

women, age 18 to 26 

participant and maternal survey, methods not clear 

DSM-IV criteria for major depression 

dth

Weissman 2005 

3 - Generation Study U.S. 

longitudinal retrospective cohort 

161 grandchildren 

of original cohort (generation 3) children of original cohort (generation 2) 

clinical assessment of generations one and two of three generation cohort study 

best estimate diagnosis, DSM-IV criteria for major depressive disorder, mood disorder 

d

Abbreviations: CIDI=composite international diagnostic interview; DSM III-R=diagnostic and statistical method of mental disorders third edition-revistatistical method of mental disorders fourth edition; FH=family history; GAS=global assessment scale; MDD=major depressive disorder; n=number ocontrolled study; U.S.=United States of America; y=years 
Webtable 26. Predictive values associated with FH definitions for mood disorders in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV fostudy sampl

B MDD, ≥1 

parent 

N N Weissman, 

M&F, onset ≤26y 

18.6 59.6 0.24 0.89 

B MDD, ≥1 

grandparent 

N N Weissman, 

M&F, onset ≤26y 

18.6 62.7 0.25 0.92 

B MDD, ≥1 

parent and ≥1 grandparent 

N N Weissman, 

M&F, onset ≤26y 

18.6 44.1 0.31 0.91 

Abbreviations: FH=family history; FU=followup; MDD=major depressive disorder; N=no; NPV=negative predictive value; NR=not reported; PPV=p

RR=relative risk; y=years 

1 RR=relative risk, metric reported unless otherwise stated 

C-60
Webtable 27. Predictive values associated with FH definitions for major depressive disorder in longitudinal analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%)

Prevalence of positive FH in study sample (%) 

PPV for study sample

NPV fostudy sample

B Weissman, 

M&F, onset ≤26y 

11.2 59.6 0.14 0.92 

B 

≥1 grandparent 

N N Weissman, 

M&F, onset ≤26y 

11.2 62.7 0.15 0.95 

B 

≥1 parent and 

≥1 

grandparent 

N N Weissman, 

M&F, onset ≤26y 

11.2 44.1 0.18 0.94 

Abbreviations: F=female; FH=family history; FU=followup; N=no; NPV=negative predictive value; M=male; NR=not reported; PPV=positive predic

y=years 

1 RR=relative risk, metric reported unless otherwise stated 

C-61
 Webtable 28. Predictive values associated with FH definitions for major depressive disorder in cross-sectional analyses

FH category 

Specific definition 

Age criterion 

Lineage criterion 

Studies Disease 

prevalence in study sample (%) 

Prevalence of positive FH in study sample (%) 

PPV for study sample 

NPV fostudy sample 

B 

≥1 parent N N Reinherz,M

&F, onset ≤26y 

23.2 16.9 0.33 0.79 

B 

≥1 sibling N N Reinherz,M

&F, onset ≤26y 

23.2 6.2 0.45 0.78 

Abbreviations: F=female; FH=family history; N=no; NPV=negative predictive value; M=male; OR=odds ratio; PPV=positive predictive value; y=yea1 OR=odds ratio, metric reported unless otherwise stated 

C-62
C-63

Webtable 29. Quality items for mental illness studies for review question 1 

Author  Year 

Same outcome ascertainment, irrespective of FH (outcome information bias) 

Outcome ascertainment blind to FH (outcome information bias) 

Same FH ascertainment, irrespective of disease status (exposure information bias) 

FH ascertainment blind to disease status (exposure information bias) 

Exclusion of cases at inception (cohort) (misclassification) 

Adequate followup (cohort) (selection bias) 

Representaive sampling (crosssectional) (selection bias) 

Mental illness Weissman 2005 

Yes Yes Yes Yes Yes at least 80% 

followup 

Not applicable (longitudinal design) 

Reinherz 2003 

Yes No Unclear Unclear Not 

applicable (crosssectional design) 

Not applicable (crosssectional design) 

Yes (probability sampling) 
Webtable 30. Studies excluded from Question 3 and Question 4 because of study design 

Studies (stratified by design) Question exclusion 

Case-control 

Andersen (2002) Q4 

Bloom (2006) Q3/Q4 

Bottorff (2002) Q4 

Cappelli (2001) Q4 

Cappelli (1999) Q4 

Drossaert (1996) Q3/Q4 

Imperiale (2008) Q3/Q4 

Kaikkonen (2006) Q3/Q4 

Meschia (2006) Q3/Q4 

Perez (2001) Q4 

Tung (2004) Q3/Q4 

Cohort

Calvocoressi (2004) Q4 

Chang (2005) Q3 

Clavel-Chapelon (1999) Q4 

Cobbe (1997) Q3/Q4 

Gil (2003) Q3/Q4 

Phillips (2005) Q3/Q4 

Sellers (1997) Q3/Q4 

Thalib (2004) Q3/Q4 

van Dooren (2005) Q4 

Cross-sectional

Armstrong (2002) Q3/Q4 

Beebe-Dimmer (2004) Q3/Q4 

Bratt (1997) Q4 

Bunn (2002) Q3/Q4 

Cantor (2002) Q4 

Carney (2006) Q4 

Cohen (2006) Q3/Q4 

Costanza (2005) Q4 

Crepeau (2008) Q4 

Criqui (2007) Q3/Q4 

Davids (2004) Q3/Q4 

Dawson (1997) Q4 

Dotterud (1995) Q3 

Drescher (2000) Q3/Q4 

Easton (1996) Q3/Q4 

Erblich (2000) Q4 

Erblich (2000) Q4 

Finney (2001) Q3/Q4 

Fletcher (2007) Q3/Q4 

Friedman (2004) Q3/Q4 

Gaga (2005) Q3/Q4 

Glanz (1999) Q4 

Harpaz (2004) Q3/Q4 

Hebert-Croteau (1997) Q4 

Higgins (2005) Q3/Q4 

Jacobsen (2004) Q4 

Karliner (2007) Q3/Q4 

Laukkanen (2007) Q3/Q4 

C-64
Webtable 30. Studies excluded from Question 3 and Question 4 because of study design(continued) 

Lippert (1999) Q4 

Longacre (2006) Q4 

Lopez-Perez Q3 

MacDonald (2005) Q4 

McCusker (2004) Q3/Q4 

Mellon (2008) Q4 

Murff (2005) Q3/Q4 

Murff (2004) Q3/Q4 

Petersen (1999) Q3/Q4 

Quillin (2006) Q4 

Robb (2004) Q4 

Roncaglioni (2004) Q4 

Rose (1999) Q3/Q4 

Scheuner (2006) Q3/Q4 

Shirakawa (2006) Q3/Q4 

Stark (2006) Q4 

Stoney (1999) Q4 

Tozzi (2008) Q3/Q4 

Van Der Sande (2001) Q3/Q4 

Wang (2006) Q3 

West (2003) Q3/Q4 

Zheng (2006) Q3/Q4 

C-65
Webfigure 1. Cancer, risk of bias 

Cancer: Risk of Bias Assessment

0% 20% 40% 60% 80% 100 %

Spectrum Bias

Selection Bias

Partial Verification Bias

Differential Verification Bias

Replicable Index Test

Replicable Reference Test

Masking Index Test

Masking Reference Test

Withdrawals

ABSENT

UNCLEAR

PRESENT

C-66
 Webfigure 2. Mental health disorders, risk of bias 

Mental Health Disorders: Risk of Bias 

Assessment

0% 20% 40% 60% 80% 100 %

Spectrum Bias

Selection Bias

Partial Verification Bias

Differential Verification Bias

Replicable Index Test

Replicable Reference Test

Masking Index Test

Masking Reference Test

Withdrawals

ABSENT

UNCLEAR

PRESENT

C-67
Webfigure 3. Parkinson’s Disease, risk of bias 

Parkinson's Disease: Risk of Bias Assessment

0% 20% 40% 60% 80% 100%

Spectrum Bias

Selection Bias

Partial Verification Bias

Differential Verification Bias

Replicable Index Test

Replicable Reference Test

Masking Index Test

Masking Reference Test

Withdrawals

ABSENT

UNCLEAR

PRESENT

C-68
Webfigure 4. Diabetes, risk of bias 

Diabetes: Risk of Bias Assessment

0% 20% 40% 60% 80% 100

%

Spectrum Bias

Selection Bias

Partial Verification Bias

Differential Verification Bias

Replicable Index Test

Replicable Reference Test

Masking Index Test

Masking Reference Test

Withdrawals

ABSENT

UNCLEAR

PRESENT

C-69
C-70

Webfigure 5. Cardiovascular disease and hypertension, risk of bias 

Cardiovascular Diseases and Hypertension: Risk 

of Bias Assessment

0% 20% 40% 60% 80% 100

%

Spectrum Bias

Selection Bias

Partial Verification Bias

Differential Verification Bias

Replicable Index Test

Replicable Reference Test

Masking Index Test

Masking Reference Test

Withdrawals

ABSENT

UNCLEAR

PRESENT
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71. 

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Rodriguez C, Calle EE, Miracle-McMahill HL, et al. 

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Scheuner MT, Whitworth WC, McGruder H, et al. 

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Sellers TA, Mink PJ, Cerhan JR, et al. The role of hormone 

replacement therapy in the risk for breast cancer and total 

mortality in women with a family history of breast cancer. 

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Sesso HD, Lee IM, Gaziano JM, et al. Maternal and 

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Shirakawa T, Ozono R, Kasagi F, et al. Differential impact 

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prevalence of hypertension and diabetes in male Japanese 

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Stark JR, Bertone-Johnson ER, Costanza ME, et al. Factors 

associated with colorectal cancer risk perception: the role 

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Stoney CM, Hughes JW. Lipid reactivity among men with 

a parental history of myocardial infarction. 

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Sugimori H, Miyakawa M, Yoshida K, et al. Health risk 

assessment for diabetes mellitus based on longitudinal 

analysis of MHTS database. J Med Syst 1998;22(1):27-32. 

Sugiyama T, Sugiyama K, Toda M, et al. Risk factors for 

asthma and allergic diseases among 13-14-year-old 

schoolchildren in Japan. Allergol Int 2002;51(2):139-50. 

Tariq SM, Matthews SM, Hakim EA, et al. The prevalence 

of and risk factors for atopy in early childhood: A whole 

population birth cohort study. J Allergy Clin Immunol 

1998;101(5):587-93. 

Thalib L, Wedren S, Granath F, et al. Breast cancer 

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cancer. Br J Cancer 2004;90(7):1378-81. 

Tozzi F, Prokopenko I, Perry JD, et al. Family history of 

depression is associated with younger age of onset in 

patients with recurrent depression. Psychol Med 

2008;38(5):641-9. 

Tung KH, Goodman MT, Wu AH, et al. Aggregation of 

ovarian cancer with breast, ovarian, colorectal, and prostate 

cancer in first-degree relatives. Am J Epidemiol 

2004;159(8):750-8. 

Van Der Sande MA, Walraven GE, Milligan PJ, et al. 

Family history: an opportunity for early interventions and 

improved control of hypertension, obesity and diabetes. 

Bull World Health Organ 2001;79(4):321-8. 

van Dooren S, Seynaeve C, Rijnsburger AJ, et al. The 

impact of having relatives affected with breast cancer on 

psychological distress in women at increased risk for 

hereditary breast cancer. Breast Cancer Res Treat 

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Wang IJ, Guo YL, Hwang KC, et al. Genetic and 

environmental predictors for pediatric atopic dermatitis. 

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Wei EK, Giovannucci E, Wu K, et al. Comparison of risk 

factors for colon and rectal cancer. Int J Cancer 

2004;108(3):433-42. 

Weissman MM, Wickramaratne P, Nomura Y, et al. 

Families at high and low risk for depression: a 3-generation 

study. Arch Gen Psychiatry 2005;62(1):29-36. 

West DS, Greene PG, Kratt PP, et al. The impact of a 

family history of breast cancer on screening practices and 

attitudes in low-income, rural, African American women. J 

Womens Health (Larchmt) 2003;12(8):779-87. 

Zheng YF, Saito T, Takahashi M, et al. Factors associated 

with intentions to adhere to colorectal cancer screening 

follow-up exams. BMC Public Health 2006;6:272 
Appendix D – Excluded Studies 

EUROASPIRE. A European Society of Cardiology survey 

of secondary prevention of coronary heart disease: 

principal results. EUROASPIRE Study Group. European 

Action on Secondary Prevention through Intervention to 

Reduce Events. [erratum appears in Eur Heart J 1998 

Feb;19(2):356-7]. Eur Heart J 1997 Oct;18(10):1569-82. 

Excluded because no eligible outcomes presented 

Risk factors for breast cancer in elderly women are similar 

to those for younger post-menopausal women. Evid Base 

Healthc Publ Health 2005;9(3):245-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Aasvee K, Kurvinen E, Sundvall J, et al. Aggregation of 

lipoprotein and inflammatory parameters in families with a 

history of premature myocardial infarction: the Tallinn 

myocardial infarction study. Clin Chem Lab Med 

2008;46(11):1602-8. 

Excluded because no eligible outcomes presented 

Abaitua FR, Martinez JI, Lopez RE, et al. Family history as 

a predictor for childhood hyperlipidemia. Cardiovasc Risk 

Factors 1996;6(5):277-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Abchee A, Puzantian H, Azar ST, et al. Predictors of 

coronary artery disease in the Lebanese population. 

Thromb Res 2006;117(6):631-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Aberg N, Sundell J, Eriksson B, et al. Prevalence of allergic 

diseases in schoolchildren in relation to family history, 

upper respiratory infections, and residential characteristics. 

Allergy 1996;51(4):232-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Acheson LS, Zyzanski SJ, Stange KC, et al. Validation of a 

self-administered, computerized tool for collecting and 

displaying the family history of cancer. J Clin Oncol 

2006;Dec 1;24(34):5395-402. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ackermann S, Lux MP, Fasching PA, et al. Acceptance for 

preventive genetic testing and prophylactic surgery in 

women with a family history of breast and gynaecological 

cancers. Eur J Cancer Prev 2006 Dec;15(6):474-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Acton RT, Burst NM, Casebeer L, et al. Knowledge, 

attitudes, and behaviors of Alabama's primary care 

physicians regarding cancer genetics. Acad Med 2000 

Aug;75(8):850-2. 

Excluded because no eligible outcomes presented 

Acton RT, Barton JC, Passmore LV, et al. Accuracy of 

Family History of Hemochromatosis or Iron Overload: The 

Hemochromatosis and Iron Overload Screening Study. Clin 

Gastroenterol Hepatol 2008;6(8):934-8. 

Excluded because not an eligible population 

Adamson AJ, Foster E, Butler TJ, et al. Non-diabetic 

relatives of Type 2 diabetic families: dietary intake 

contributes to the increased risk of diabetes. Diabet Med 

2001 Dec;18(12):984-90. 

Excluded because no eligible outcomes presented 

Aggarwal AN, Chaudhry K, Chhabra SK, et al. Prevalence 

and risk factors for bronchial asthma in Indian adults: a 

multicentre study. Indian J Chest Dis Allied SciI 2006 

Jan;48(1):13-22. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Aghassi-Ippen M, Green MS, Shohat T. Familial risk 

factors for breast cancer among Arab women in Israel. Eur 

J Cancer Prev 2002 Aug;11(4):327-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ahsan H, Neugut AI, Garbowski GC, et al. Family history 

of colorectal adenomatous polyps and increased risk for 

colorectal cancer. Ann Intern Med 1998 Jun 1;128(11):900-

5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Aitken JF, Bain CJ, Ward M, et al. Risk of colorectal 

adenomas in patients with a family history of colorectal 

cancer: some implications for screening programmes. Gut 

1996 Jul;39(1):105-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-1
Ajay VS, Prabhakaran D, Jeemon P, et al. Prevalence and 

determinants of diabetes mellitus in the Indian industrial 

population. Diabet Med 2008;25(10):1187-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Akesson K, Nystrom L, Farnkvist L, et al. Increased risk of 

diabetes among relatives of female insulin-treated patients 

diagnosed at 15-34 years of age. Diabet Med 2005 

Nov;22(11):1551-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Akimova EV, Bogmat LF. Premature coronary heart 

disease: the influence of positive family history on platelet 

activity in vivo in children and adolescents (family study). J 

Cardiovasc Risk 1997 Feb;4(1):13-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Akkurt I, Sumer H, Ozsahin SL, et al. Prevalence of asthma 

and related symptoms in Sivas, Central Anatolia. J Asthma 

2003;40(5):551-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Al Bassam MKS, Al Awar S, Khan F, et al. Universal 

screening strategy for gestational diabetes mellitus: The 

experience of Tawam Hospital. Emirates Medical Journal 

2007;25(3):307-10. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Al Habsi H, Lim JNW, Chu CE, et al. Factors influencing 

the referrals in primary care of asymptomatic patients with 

a family history of cancer. Genet Med 2008;10(10):751-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Al Mahroos F, McKeigue PM. High prevalence of diabetes 

in bahrainis: Associations with ethnicity and raised plasma 

cholesterol. Diabetes Care 1998;21(6):936-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Al Rukban MO, Al Sughair AM, Al Bader BO, et al. 

Management of hypertensive patients in primary health 

care setting, auditing the practice. Saudi Med J 

2007;28(1):85-90. 

Excluded because family history not collected 

Al Saeed WY, Al Dawood KM, Bukhari IA, et al. Risk 

factors and co-morbidity of skin disorders among female 

schoolchildren in eastern Saudi Arabia. Invest Clin 

2007;48(2):199-212. 

Excluded because no eligible outcomes presented 

Al Safi SA, Aboul-Enein FH, Aboul-Enein BH, et al. 

Influence of family history and lifestyle on blood pressure 

and heart rate in young adults in Jordan. Public Health 

2006 Nov;120(11):1027-32. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Al Shafaee MA, Al Shukaili S, Rizvi SGA, et al. 

Knowledge and perceptions of diabetes in a semi-urban 

Omani population. BMC Public Health 2008;8:249. 

Excluded because no eligible outcomes presented 

Al Shaibani H, Bu-Alayyan S, Habiba S, et al. Risk factors 

of breast cancer in Kuwait: Case-control study. Iranian 

Journal of Medical Sciences 2006;31(2):61-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Alberto VO, Harocopos CJ, Patel AA, et al. Family and 

personal history in colorectal cancer patients: what are we 

missing? Colorectal Dis 2006 Sep;8(7):612-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Aldington S, Pritchard A, Perrin K, et al. Prolonged seated 

immobility at work is a common risk factor for venous 

thromboembolism leading to hospital admission. Intern 

Med J 2008;38(2):133-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Allan CL, Flett B, Dean HJ. Quality of life in first nation 

youth with type 2 diabetes. Matern Child Health J 

2008;12(Suppl 1):S103-S109 

Excluded because no eligible outcomes presented 

Allinson V. Breast cancer: evaluation of a nurse-led family 

history clinic. J Clin Nurs 2004 Sep;13(6):765-6. 

Excluded because no eligible outcomes presented 

Almendingen K, Hofstad B, Vatn MH. Does a family 

history of cancer increase the risk of occurrence, growth, 

and recurrence of colorectal adenomas? Gut 2003 

May;52(5):747-51. 

D-2
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Altobelli E, Chiarelli F, Valenti M, et al. Family history 

and risk of insulin-dependent diabetes mellitus: a 

population-based case-control study. Acta Diabetol 1998 

Apr;35(1):57-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Amberger N, Masuhr F, Valdueza JM, et al. A negative 

personal and family history for venous thrombotic events is 

not sufficient to exclude thrombophilia in patients with 

cerebral venous thrombosis. Eur J Neurol 2004 

Aug;11(8):555-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ammari F, Batieha A, Jaddou PHH, et al. A natural history 

of impaired glucose tolerance in North Jordan. Pract 

Diabetes Int 1998;15(5):139-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Andermann AAJ, Watson EK, Lucassen AM, et al. The 

opinions, expectations and experiences of women with a 

family history of breast cancer who consult their GP and 

referred to secondary care. Community Genet 

2001;4(4):239-43. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Andersen MR, Peacock S, Nelson J, et al. Worry about 

ovarian cancer risk and use of ovarian cancer screening by 

women at risk for ovarian cancer. Gynecol Oncol 2002 

Apr;85(1):3-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Andersen MR, Bowen D, Yasui Y, et al. Awareness and 

concern about ovarian cancer among women at risk 

because of a family history of breast or ovarian cancer. Am 

J Obstet Gynecol 2003 Oct;189(4 Suppl):S42-S47 

Excluded because no eligible outcomes presented 

Andersen MR, Smith R, Meischke H, et al. Breast cancer 

worry and mammography use by women with and without 

a family history in a population-based sample. Cancer 

Epidemiol Biomarkers Prev 2003 Apr;12(4):314-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Anderson E, Berg J, Black R, et al. Predicting breast cancer 

risk: Implications of a "weak" family history. Fam Cancer 

2008;7(4):361-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Anderson WF, Matsuno RK, Sherman ME, et al. 

Estimating age-specific breast cancer risks: A descriptive 

tool to identify age interactions. Cancer Causes Control 

2007;18(4):439-47. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Andersson SO, Baron J, Bergstrom R, et al. Lifestyle 

factors and prostate cancer risk: A case-control study in 

Sweden. Cancer Epidemiol Biomarkers Prev 

1996;5(7):509-13. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Andresdottir MB, Sigurdsson G, Sigvaldason H, et al. 

Fifteen percent of myocardial infarctions and coronary 

revascularizations explained by family history unrelated to 

conventional risk factors. The Reykjavik Cohort Study. Eur 

Heart J 2002 Nov;23(21):1655-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Andrieu N, Launoy G, Guillois R, et al. Estimation of the 

familial relative risk of cancer by site from a French 

population based family study on colorectal cancer 

(CCREF study). Gut 2004 Sep;53(9):1322-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Aprikian AG, Bazinet M, Plante M, et al. Family history 

and the risk of prostatic carcinoma in a high risk group of 

urological patients. J Urol 1995 Aug;154(2:Pt 1):404-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Arabia G, Grossardt BR, Geda YE, et al. Increased risk of 

depressive and anxiety disorders in relatives of patients 

with Parkinson disease. Arch Gen Psychiatry 2007 

Dec;64(12):1385-92. 

D-3
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Arif AA, Venati G, Bordes TF, et al. Correlates of 

physician visits among children and adolescents in West 

Texas: Effects of hyperglycemia symptoms. J Rural Health 

2004;20(3):296-300. 

Excluded because no eligible outcomes presented 

Armstrong K, Weber B, Ubel PA, et al. Interest in 

BRCA1/2 testing in a primary care population. Prev Med 

2002;34(6):590-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Arsov T, Miladinova D, Spiroski M. Factor V Leiden is 

associated with higher risk of deep venous thrombosis of 

large blood vessels. Croat Med J 2006;47(3):433-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ashton KA, Proietto A, Otton G, et al. The influence of the 

Cyclin D1 870 G>A polymorphism as an endometrial 

cancer risk factor. BMC Cancer 2008 Sep;8:272. 

Excluded because no eligible outcomes presented 

Askling J, Dickman PW, Karlen P, et al. Family history as 

a risk factor for colorectal cancer in inflammatory bowel 

disease. Gastroenterology 2001 May;120(6):1356-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Auranen A, Grenman S, Makinen J, et al. Borderline 

ovarian tumors in Finland: epidemiology and familial 

occurrence. Am J Epidemiol 1996 Sep 15;144(6):548-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Azadeh S, Moghimi-Dehkordi B, Fatem SR, et al. 

Colorectal cancer in Iran: an epidemiological study. Asian 

Pac J Cancer Prev 2008 Jan;9(1):123-6. 

Excluded because no eligible outcomes presented 

Babaoglu K, Hatun S, Arslanoglu I, et al. Evaluation of 

glucose intolerance in adolescents relative to adults with 

type 2 diabetes mellitus. J Pediatr Endocrinol 2006 

Nov;19(11):1319-26. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Backlund AB, Perzanowski MS, Platts-Mills T, et al. 

Asthma during the primary school ages - Prevalence, 

remission and the impact of allergic sensitization. Allergy 

2006;61(5):549-55. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bai Y, Gao YT, Deng J, et al. Risk of prostate cancer and 

family history of cancer: a population-based study in 

China. Prostate Cancer Prostatic Dis 2005;8(1):60-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bajdik CD, Fang R, Band PR, et al. Do work-related breast 

cancer risks in pre-menopausal women depend on family 

history? Chronic Dis Can 2004;25(3-4):147-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Baldwin RC, Tomenson B. Depression in later life. A 

comparison of symptoms and risk factors in early and late 

onset cases. Br J Psychiatry 1995 Nov;167:649-52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bank I, van de Poel MH, Coppens M, et al. Absolute 

annual incidences of first events of venous 

thromboembolism and arterial vascular events in 

individuals with elevated FVIII:c. A prospective family 

cohort study. Thromb Haemost 2007 Nov;98(5):1040-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bankhead C, Emery J, Qureshi N, et al. New developments 

in genetics-knowledge, attitudes and information needs of 

practice nurses. Fam Pract 2001 Oct;18(5):475-86. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bao W, Srinivasan SR, Wattigney WA, et al. The relation 

of parental cardiovascular disease to risk factors in children 

and young adults. The Bogalusa Heart Study. Circulation 

1995 Jan 15;91(2):365-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bao W, Srinivasan SR, Valdez R, et al. Longitudinal 

changes in cardiovascular risk from childhood to young 

D-4
adulthood in offspring of parents with coronary artery 

disease: The Bogalusa heart study. JAMA 

1997;278(21):1749-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Barlow-Stewart K, Soo SY, Meiser B, et al. Toward 

cultural competence in cancer genetic counseling and 

genetics education: Lessons learned from ChineseAustralians. Genet Med 2006;8(1):24-32. 

Excluded because not an eligible study design 

Barone B, Rodacki M, Zajdenverg L, et al. Family history 

of type 2 diabetes is increased in patients with type 1 

diabetes. Diabetes Res Clin Practice 2008 Oct;82(1):e1-e4 

Excluded because no eligible outcomes presented 

Barrison AF, Smith C, Oviedo J, et al. Colorectal cancer 

screening and familial risk: a survey of internal medicine 

residents' knowledge and practice patterns. Am J 

Gastroenterol 2003 Jun;98(6):1410-6. 

Excluded because family history not collected 

Barth JA, Deckelbaum RJ, Starc TJ, et al. Family history of 

early cardiovascular disease in children with moderate to 

severe hypercholesterolemia: relationship to lipoprotein (a) 

and low-density lipoprotein cholesterol levels. J Lab Clin 

Med 1999 Mar;133(3):237-44. 

Excluded because no eligible outcomes presented 

Basit A, Hakeem R, Hydrie MZ, et al. Fatness, lipids, 

insulin sensitivity, and life style of children from high and 

low risk families. J Ayub Med Coll Abbottabad 2003 

Jul;15(3):6-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Basit A, Hakeem R, Hydrie MZI, et al. Relation between 

family history, obesity and risk for diabetes & heart disease 

in Pakistani children. Pakistan J Med Sci 2004;20(4):296-

302. 

Excluded because no eligible outcomes presented 

Bastani R, Maxwell AE, Bradford C, et al. Tailored risk 

notification for women with a family history of breast 

cancer. Prev Med 1999 Nov;29(5):355-64. 

Excluded because not an eligible population 

Bayram I, Guneser-Kendirli S, Yilmaz M, et al. The 

prevalence of asthma and allergic diseases in children of 

school age in Adana in Southern Turkey. Turk J Pediatr 

2004;46(3):221-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bazzazi H, Gharagozlou M, Kassaiee M, et al. The 

prevalence of asthma and allergic disorders among school 

children in Gorgan. J Res Med Sci 2007;12(1):28-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Beebe-Dimmer JL, Wood DP, Jr., Gruber SB, et al. Risk 

perception and concern among brothers of men with 

prostate carcinoma. Cancer 2004 Apr 1;100(7):1537-44. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Beebe-Dimmer JL, Drake EA, Dunn RL, et al. Association 

between family history of prostate and breast cancer among 

African-American men with prostate cancer. Urology 2006 

Nov;68(5):1072-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Beji NK, Reis N. Risk factors for breast cancer in Turkish 

women: a hospital-based case-control study. Eur J Cancer 

Care 2007 Mar;16(2):178-84. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Benazzi F. Unipolar depression with bipolar family history: 

Links with the bipolar spectrum. Psychiatry Clin Neurosci 

2003;57(5):497-503. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Benazzi F. Bipolar II disorder family history using the 

family history screen: findings and clinical implications. 

Compr Psychiatry 2004 Mar;45(2):77-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Benhamiche-Bouvier AM, Lejeune C, Jouve JL, et al. 

Family history and risk of colorectal cancer: implications 

for screening programmes. J Med Screen 2000;7(3):136-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Benjamin C, Booth K, Ellis I. A prospective comparison 

study of different methods of gathering self-reported family 

history information for breast cancer risk assessment. J 

Genet Couns 2003;12(2):151-70. 

D-5
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bennett KE, Howell A, Evans DG, et al. A follow-up study 

of breast and other cancers in families of an unselected 

series of breast cancer patients. Br J Cancer 2002 Mar 

4;86(5):718-22. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bensen JT, Li R, Hutchinson RG, et al. Family history of 

coronary heart disease and pre-clinical carotid artery 

atherosclerosis in African-Americans and whites: the ARIC 

study: Atherosclerosis Risk in Communities. Genet 

Epidemiol 1999;16(2):165-78. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bergfeldt K, Rydh B, Granath F, et al. Risk of ovarian 

cancer in breast-cancer patients with a family history of 

breast or ovarian cancer: a population-based cohort study. 

Lancet 2002 Sep 21;360(9337):891-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bergmann RL, Diepgen TL, Kuss O, et al. Breastfeeding 

duration is a risk factor for atopic eczema. Clin Exp 

Allergy 2002 Feb;32(2):205-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bergstrom E, Hernell O, Persson LA, et al. Serum lipid 

values in adolescents are related to family history, infant 

feeding, and physical growth. Atherosclerosis 1995 

Sep;117(1):1-13. 

Excluded because no eligible outcomes presented 

Bermejo JL, Hemminki K. Familial risk of cancer shortly 

after diagnosis of the first familial tumor. J Natl Cancer Inst 

2005 Nov 2;97(21):1575-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bertuzzi M, Negri E, Tavani A, et al. Family history of 

ischemic heart disease and risk of acute myocardial 

infarction. Prev Med 2003 Sep;37(3):183-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bhatia S, Pratt CB, Sharp GB, et al. Family history of 

cancer in children and young adults with colorectal cancer. 

Med Pediatr Oncol 1999 Nov;33(5):470-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bindler RM, Short RA, Cooney SK, et al. Interventions to 

decrease cardiovascular risk factors in children: The 

Northwest Pediatric Heart Project. National Academies of 

Practice Forum: Issues in Interdisciplinary Care 2000 

Jan;2(1):43-8. 

Excluded because no eligible outcomes presented 

Bjerg A, Hedman L, Perzanowski MS, et al. Family history 

of asthma and atopy: in-depth analyses of the impact on 

asthma and wheeze in 7- to 8-year-old children. Pediatrics 

2007 Oct;120(4):741-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bloom JR, Stewart SL, Oakley-Girvans I, et al. Family 

history, perceived risk, and prostate cancer screening 

among African American men. Cancer Epidemiol 

Biomarkers Prev 2006 Nov;15(11):2167-73. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bock CH, Peyser PA, Montie JE, et al. Decreasing age at 

prostate cancer diagnosis over successive generations in 

prostate cancer families. Prostate 2005 Jun 15;64(1):60-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bodner C, Godden D, Ross S, et al. Bronchial 

hyperresponsiveness and adult onset wheeze: the influence 

of atopy. Eur Respir J 1999 Aug;14(2):335-8. 

Excluded because no eligible outcomes presented 

Boer JM, Feskens EJ, Verschuren WM, et al. The joint 

impact of family history of myocardial infarction and other 

risk factors on 12-year coronary heart disease mortality. 

Epidemiology 1999 Nov;10(6):767-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bohme M, Wickman M, Lennart NS, et al. Family history 

and risk of atopic dermatitis in children up to 4 years. Clin 

Exp Allergy 2003 Sep;33(9):1226-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-6
and outcome criteria were met for the review questions in 

aggregate 

Boice JD, Jr., Mandel JS, Doody MM. Breast cancer 

among radiologic technologists. JAMA 1995 Aug 

2;274(5):394-401. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Boilesen AE, Bisgaard ML, Bernstein I. Risk of 

gynecologic cancers in Danish hereditary non-polyposis 

colorectal cancer families. Acta Obstet Gynecol Scand 

2008;87(11):1129-35. 

Excluded because not an eligible population 

Boles RG, Burnett BB, Gleditsch K, et al. A high 

predisposition to depression and anxiety in mothers and 

other matrilineal relatives of children with presumed 

maternally inherited mitochondrial disorders. Am J Med 

Genet Neuropsychiatr Genet 2005;137(1):20-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bonduel M, Hepner M, Sciuccati G, et al. Prothrombotic 

abnormalities in children with venous thromboembolism. J 

Pediatr Hematol Oncol 2000;22(1):66-72. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bor AS, Rinkel GJ, Adami J, et al. Risk of subarachnoid 

haemorrhage according to number of affected relatives: a 

population based case-control study. Brain 2008 

Oct;131(Pt:10):10-5. 

Excluded because no eligible outcomes presented 

Borio R, Forini N, Salvadori P, et al. Risk versus benefit in 

mammographic screening procedures. Physica Medica 

1997;13(4):173-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Borres MP, Bjorksten B. Peripheral blood eosinophils and 

IL-4 in infancy in relation to the appearance of allergic 

disease during the first 6 years of life. Pediatr Allergy 

Immunol 2004;15(3):216-20. 

Excluded because no eligible outcomes presented 

Bosken CH, Hunt WC, Lambert WE, et al. A parental 

history of asthma is a risk factor for wheezing and 

nonwheezing respiratory illnesses in infants younger than 

18 months of age. Am J Respir Crit Care Med 2000 

Jun;161(6):1810-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bosson J-L, Pouchain D, Bergmann J-F. A prospective 

observational study of a cohort of outpatients with an acute 

medical event and reduced mobility: Incidence of 

symptomatic thromboembolism and description of 

thromboprophylaxis practices. J Intern Med 

2006;260(2):168-76. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bottorff JL, Ratner PA, Balneaves LG, et al. Women's 

interest in genetic testing for breast cancer risk: the 

influence of sociodemographics and knowledge. Cancer 

Epidemiol Biomarkers Prev 2002 Jan;11(1):89-95. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Boucher KM, Kerber RA. Measures of familial aggregation 

as predictors of breast-cancer risk. J Epidemiol Biostat 

2001;6(5):377-85. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Boulton TJ, Cockington RA, Hamilton-Craig I, et al. A 

profile of heart disease risk factors and their relation to 

parents' education, fathers' occupation and family history of 

heart disease in 843 South Australian families: the Adelaide 

Children's WHO Collaborative Study. J Paediatr Child 

Health 1995 Jun;31(3):200-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Boutet K, Malo J-L, Ghezzo H, et al. Airway 

hyperresponsiveness and risk of chest symptoms in an 

occupational model. Thorax 2007;62(3):260-4. 

Excluded because no eligible outcomes presented 

Boutin-Foster C, Ogedegbe G, Ravenell JE, et al. Ascribing 

meaning to hypertension: A qualitative study among 

African Americans with uncontrolled hypertension. Ethn 

Dis 2007;17(1):29-34. 

Excluded because not an eligible study design 

Boutron MC, Faivre J, Quipourt V, et al. Family history of 

colorectal tumours and implications for the adenomacarcinoma sequence: a case control study. Gut 1995 

Dec;37(6):830-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-7
Bowen DJ, Helmes A, Powers D, et al. Predicting breast 

cancer screening intentions and behavior with emotion and 

cognition. J Soc Clin Psychol 2003 Jun;22(2):213-32. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Boyd NF, Lockwood GA, Martin LJ, et al. Mammographic 

densities and risk of breast cancer among subjects with a 

family history of this disease. J Natl Cancer Inst 1999 Aug 

18;91(16):1404-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brain K, Norman P, Gray J, et al. Anxiety and adherence to 

breast self-examination in women with a family history of 

breast cancer. Psychosom Med 1999 Mar;61(2):181-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brain K, Henderson BJ, Tyndel S, et al. Predictors of breast 

cancer-related distress following mammography screening 

in younger women on a family history breast screening 

programme. Psychooncology 2008 Dec;17(12):1180-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Braithwaite D, Sutton S, Smithson WH, et al. Internetbased risk assessment and decision support for the 

management of familial cancer in primary care: a survey of 

GPs' attitudes and intentions. Fam Pract 2002 

Dec;19(6):587-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brandt A, Bermejo JL, Sundquist J, et al. Age of onset in 

familial cancer. Ann Oncol 2008;19(12):2084-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bratt O, Kristoffersson U, Lundgren R, et al. Sons of men 

with prostate cancer: Their attitudes regarding possible 

inheritance of prostate cancer, screening, and genetic 

testing. Urology 1997;50(3):360-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bratt O, Kristoffersson U, Lundgren R, et al. Familial and 

hereditary prostate cancer in southern Sweden. A 

population-based case-control study. Eur J Cancer 1999 

Feb;35(2):272-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bravi F, Bosetti C, Negri E, et al. Family history of cancer 

provided by hospital controls was satisfactorily reliable. J 

Clin Epidemiol 2007 Feb;60(2):171-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brawley A, Silverman B, Kearney S, et al. Allergic rhinitis 

in children with attention-deficit/hyperactivity disorder. 

Ann AllergyAsthma Immunol 2004;92(6):663-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brinton LA, Richesson DA, Gierach GL, et al. Prospective 

evaluation of risk factors for male breast cancer. J Natl 

Cancer Inst 2008;100(20):1477-81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bromen K, Pohlabeln H, Jahn I, et al. Aggregation of lung 

cancer in families: results from a population-based casecontrol study in Germany. Am J Epidemiol 2000 Sep 

15;152(6):497-505. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brown DW, Giles WH, Burke W, et al. Familial 

aggregation of early-onset myocardial infarction. 

Community Genet 2002;5(4):232-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brown N, Naman P, Homel P, et al. Assessment of 

preventive health knowledge and behaviors of AfricanAmerican and Afro-Caribbean women in urban settings. J 

Natl Med Assoc 2006;98(10):1644-51. 

Excluded because no eligible outcomes presented 

Brown SR, Finan PJ, Bishop DT. Are relatives of patients 

with multiple HNPCC spectrum tumours at increased risk 

of cancer? Gut 1998 Nov;43(5):664-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-8
Brownson RC, Alavanja MC, Caporaso N, et al. Family 

history of cancer and risk of lung cancer in lifetime nonsmokers and long-term ex-smokers. Int J Epidemiol 1997 

Apr;26(2):256-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Brugge D, Lee AC, Woodin M, et al. Native and foreign 

born as predictors of pediatric asthma in an Asian 

immigrant population: A cross sectional survey. Environ 

Health 2007;6:13 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bruno M, Tommasi S, Stea B, et al. Awareness of breast 

cancer genetics and interest in predictive genetic testing: A 

survey of a southern Italian population. Ann Oncol 

2004;15(Suppl 1):i48-i54 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Buccheri G, Ferrigno D. Familial and personal history of 

cancer in bronchogenic carcinoma--frequency and clinical 

implications. Acta Oncol 2004;43(1):65-72. 

Excluded because not an eligible study design 

Bucholz KK, Nurnberger J, Kramer JR, et al. Comparison 

of psychiatric diagnoses from interview reports with those 

from best-estimate procedures. J Stud Alcohol 

2006;67(1):157-68. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Bunn JY, Bosompra K, Ashikaga T, et al. Factors 

influencing intention to obtain a genetic test for colon 

cancer risk: A population-based study. Prev Med 

2002;34(6):567-77. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Burke JP, Williams K, Narayan KMV, et al. A population 

perspective on diabetes prevention: whom should we target 

for preventing weight gain? Diabetes Care 2003 

Jul;26(7):1999-2004. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Burke V, Beilin LJ, Dunbar D. Tracking of blood pressure 

in Australian children. J Hypertens 2001;19(7):1185-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Burke W, Culver JO, Bowen D, et al. Genetic counseling 

for women with an intermediate family history of breast 

cancer. Am J Med Genet 2000 Feb 28;90(5):361-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Byrne GJ, Bundred NJ. Does the evidence justify national 

funding of breast cancer family history clinics? Breast 

1997;6(6):388-93. 

Excluded because not an eligible study design 

Cabrinety N, Pisonero MJ, Ajram J, et al. Lipoprotein (a) in 

obese children with a family history of cardiovascular 

disease. J Pediatr Endocrinol 2002 Jan;15(1):77-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Caicoya M, Corrales C, Rodriguez T. Family history and 

stroke: a community case-control study in Asturias, Spain. 

J Epidemiol Biostat 1999;4(4):313-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Calbi M, Giacchetti L, Coppola A, et al. Basophil count in 

neonates is not suitable for atopy predictivity. J Investig 

Allergol Clin Immunol 1996;6(6):383-7. 

Excluded because no eligible outcomes presented 

Calderon-Garciduenas AL, Paras-Barrientos FU, CardenasIbarra L, et al. Risk factors of breast cancer in Mexican 

women. Salud Publica Mex 2000 Jan;42(1):26-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Callejas JM, Manasanch J, Abad R, et al. Epidemiology of 

chronic venous insufficiency of the lower limbs in the 

primary care setting. Int Angiol 2004;23(2):154-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Calvocoressi L, Kasl SV, Lee CH, et al. A prospective 

study of perceived susceptibility to breast cancer and 

nonadherence to mammography screening guidelines in 

African American and White women ages 40 to 79 years. 

Cancer Epidemiol Biomarkers Prev 2004;13(12):2096-105. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-9
and outcome criteria were met for the review questions in 

aggregate 

Cameron LD, Petrie KJ, Ellis C, et al. Symptom 

experiences, symptom attributions, and causal attributions 

in patients following first-time myocardial infarction. 

International J 2005;12(1):30-8. 

Excluded because no eligible outcomes presented 

Cameron LD, Reeve J. Risk perceptions, worry, and 

attitudes about genetic testing for breast cancer 

susceptibility. Psychol Health 2006 Apr;21(2):211-30. 

Excluded because no eligible outcomes presented 

Camp NJ, Slattery ML. Classification tree analysis: a 

statistical tool to investigate risk factor interactions with an 

example for colon cancer (United States). Cancer Causes 

Control 2002 Nov;13(9):813-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Campbell PT, Cotterchio M, Dicks E, et al. Excess body 

weight and colorectal cancer risk in Canada: Associations 

in subgroups of clinically defined familial risk of cancer. 

Cancer Epidemiol Biomarkers Prev 2007;16(9):1735-44. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Canani LH, Gerchman F, Gross JL. Increased familial 

history of arterial hypertension, coronary heart disease, and 

renal disease in Brazilian type 2 diabetic patients with 

diabetic nephropathy. Diabetes Care 1998 Sep;21(9):1545-

50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Canby-Hagino E, Hernandez J, Brand TC, et al. Prostate 

cancer risk with positive family history, normal prostate 

examination findings, and PSA less than 4.0 ng/mL. 

Urology 2007 Oct;70(4):748-52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cansu A, Serdaroglu A, Yuksel D, et al. Prevalence of 

some risk factors in children with epilepsy compared to 

their controls. Seizure 2007;16(4):338-44. 

Excluded because no eligible outcomes presented 

Cantor SB, Volk RJ, Cass AR, et al. Psychological benefits 

of prostate cancer screening: The role of reassurance. 

Health Expect 2002;5(2):104-13. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cappelli M, Surh L, Humphreys L, et al. Psychological and 

social determinants of women's decisions to undergo 

genetic counseling and testing for breast cancer. Clin Genet 

1999;55(6):419-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cappelli M, Surh L, Walker M, et al. Psychological and 

social predictors of decisions about genetic testing for 

breast cancer in high-risk women. Psychol Health Med 

2001;6(3):321-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Caputo S, Capozzi G, Russo MG, et al. Familial recurrence 

of congenital heart disease in patients with ostium 

secundum atrial septal defect. Eur Heart J 2005 

Oct;26(20):2179-84. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Carney PA, Steiner E, Goodrich ME, et al. Discovery of 

breast cancers within 1 year of a normal screening 

mammogram: How are they found? Ann Fam Med 

2006;4(6):512-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Carpenter CL, Ross RK, Paganini-Hill A, et al. Effect of 

family history, obesity and exercise on breast cancer risk 

among postmenopausal women. Int J Cancer 2003 Aug 

10;106(1):96-102. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Carpenter S, Broughton M, Marks CG. A screening clinic 

for relatives of patients with colorectal cancer in a district 

general hospital. Gut 1995 Jan;36(1):90-2. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Carr DB, Utzschneider KM, Hull RL, et al. Gestational 

diabetes mellitus increases the risk of cardiovascular 

disease in women with a family history of type 2 diabetes. 

Diabetes Care 2006 Sep;29(9):2078-83. 

Excluded because not an eligible population 

D-10
Caruso A, Vigna C, Maggi G, et al. The withdrawal from 

oncogenetic counselling and testing for hereditary and 

familial breast and ovarian cancer. A descriptive study of 

an Italian sample. J Exp Clin Cancer Res 2008;27:75 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Casey R, Brennan P, Becker N, et al. Influence of familial 

cancer history on lymphoid neoplasms risk validated in the 

large European case-control study epilymph. Eur J Cancer 

2006 Oct;42(15):2570-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cassidy A, Myles JP, Duffy SW, et al. Family history and 

risk of lung cancer: age-at-diagnosis in cases and firstdegree relatives. Br J Cancer 2006 Nov 6;95(9):1288-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ceballos RM, Newcomb PA, Beasley JM, et al. Colorectal 

cancer cases and relatives of cases indicate similar 

willingness to receive and disclose genetic information. 

Genet Test 2008 Sep;12(3):415-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ceber E, Sogukpinar N, Mermer G, et al. Nutrition, 

lifestyle, and breast cancer risk among Turkish women. 

Nutr Cancer 2005;53(2):152-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cerhan JR, Grabrick DM, Vierkant RA, et al. Interaction of 

adolescent anthropometric characteristics and family 

history on breast cancer risk in a historical cohort study of 

426 families (USA). Cancer Causes Control 2004;15(1):1-

9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chambers EC, Tull ES, Fraser H, et al. A family history of 

diabetes is related to abnormal insulin sensitivity in 

African-Caribbean girls of low birth weight: Is catch-up 

weight important? Ethn Dis 2005;15(3):424-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chan-Yeung M, Koo LC, Ho JCM, et al. Risk factors 

associated with lung cancer in Hong Kong. Lung Cancer 

2003;40(2):131-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chan-Yeung M, Hegele RG, Dimich-Ward H, et al. Early 

environmental determinants of asthma risk in a high-risk 

birth cohort. Pediatr Allergy Immunol 2008;19(6):482-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chan JA, Meyerhardt JA, Niedzwiecki D, et al. Association 

of family history with cancer recurrence and survival 

among patients with stage III colon cancer. JAMA 

2008;299(21):2515-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chang-Claude J, Eby N, Kiechle M, et al. Breastfeeding 

and breast cancer risk by age 50 among women in 

Germany. Cancer Causes Control 2000;11(8):687-95. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chang WT, Sun HL, Lue KH, et al. Predictability of early 

onset atopic dermatitis by cord blood IgE and parental 

history. Acta Paediatrica Taiwanica 2005 Sep;46(5):272-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chart PL, Franssen E. Management of women at increased 

risk for breast cancer: Preliminary results from a new 

program. Can Med Assoc J 1997;157(9):1235-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chaturvedi V, Reddy KS, Prabhakaran D, et al. 

Development of a clinical risk score in predicting 

undiagnosed diabetes in urban Asian Indian adults: a 

population-based study. CVD Prevention and Control 

2008;3(3):141-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chen J, Millar WJ. Heart disease, family history and 

physical activity. Health Rep 2001 Aug;12(4):23-32. 

D-11
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chen K-T, Chen C-J, Gregg EW, et al. Prevalence of type 2 

diabetes mellitus in Taiwan: Ethnic variation and risk 

factors. Diabetes Res Clin Pract 2001;51(1):59-66. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chhabra SK, Gupta CK, Chhabra P, et al. Risk factors for 

development of bronchial asthma in children in Delhi. Ann 

Allergy Asthma Immunol 1999 Nov;83(5):385-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Choi HK, De Vera MA, Krishnan E. Gout and the risk of 

type 2 diabetes among men with a high cardiovascular risk 

profile. Rheumatology (Oxford) 2008;47(10):1567-70. 

Excluded because no eligible outcomes presented 

Choi SH, Yoo Y, Yu J, et al. Bronchial 

hyperresponsiveness in young children with allergic rhinitis 

and its risk factors. Allergy 2007;62(9):1051-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Choo KE, Lau KB, Davis WA, et al. Cardiovascular risk 

factors in pre-pubertal Malays: effects of diabetic 

parentage. Diabetes Res Clin Pract 2007 Apr;76(1):119-25. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chorne-Navia R, Chatterjee N. Prevalence of family 

history of diabetes in type 2 diabetes patients in Coahuila, 

Mexico. Hispanic Health Care Int 2008;6(1):5-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Christiaans I, Birnie E, Bonsel GJ, et al. Uptake of genetic 

counselling and predictive DNA testing in hypertrophic 

cardiomyopathy. Eur J Hum Genet 2008 Oct;16(10):1201-

7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Christie GL, McDougall CM, Helms PJ. Is the increase in 

asthma prevalence occurring in children without a family 

history of atopy? Scott Med J 1998 Dec;43(6):180-2. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Chun J, El Tamer M, Joseph K-A, et al. Predictors of breast 

cancer development in a high-risk population. Am J Surg 

2006;192(4):474-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Church J, McGannon E. Family history of colorectal 

cancer: how often and how accurately is it recorded? Dis 

Colon Rectum 2000 Nov;43(11):1540-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Church JM. A scoring system for the strength of a family 

history of colorectal cancer. Dis Colon Rectum 2005 

May;48(5):889-96. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ciruzzi M, Schargrodsky H, Rozlosnik J, et al. Frequency 

of family history of acute myocardial infarction in patients 

with acute myocardial infarction. Argentine FRICAS 

(Factores de Riesgo Coronario en America del Sur) 

Investigators. Am J Cardiol 1997 Jul 15;80(2):122-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ciruzzi M, Schargrodsky H, Pramparo P, et al. Attributable 

risks for acute myocardial infarction in four countries of 

Latin America. Medicina (Mex) 2003;63(6):697-703. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Clarkson P, Celermajer DS, Powe AJ, et al. Endotheliumdependent dilatation is impaired in young healthy subjects 

with a family history of premature coronary disease. 

Circulation 1997 Nov 18;96(10):3378-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Claus EB, Schildkraut JM, Thompson WD, et al. The 

genetic attributable risk of breast and ovarian cancer. 

Cancer 1996 Jun 1;77(11):2318-24. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-12
and outcome criteria were met for the review questions in 

aggregate 

Claus EB, Stowe M, Carter D. Family history of breast and 

ovarian cancer and the risk of breast carcinoma in situ. 

Breast Cancer Res Treat 2003 Mar;78(1):7-15. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Clausen TD, Mathiesen ER, Hansen T, et al. High 

prevalence of type 2 diabetes and pre-diabetes in adult 

offspring of women with gestational diabetes mellitus or 

type 1 diabetes: the role of intrauterine hyperglycemia. 

Diabetes Care 2008 Feb;31(2):340-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Clavel-Chapelon F, Joseph R, Goulard H. Surveillance 

behavior of women with a reported family history of 

colorectal cancer. Prev Med 1999 Feb;28(2):174-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Coady MA, Davies RR, Roberts M, et al. Familial patterns 

of thoracic aortic aneurysms. Arch Surg 1999 

Apr;134(4):361-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cobbe SM. Baseline risk factors and their association with 

outcome in the West of Scotland Coronary Prevention 

Study. Am J Cardiol 1997;79(6):756-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cohen M. Breast canceer early detection, health beliefs, 

and cancer worries in randomly selected women with and 

without a family history of breast cancer. Psychooncology 

2006;15(10):873-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cohn WF, Ropka ME, Jones SM, et al. Information needs 

about hereditary breast cancer among women with earlyonset breast cancer. Cancer Detect Prev J 2003;27(5):345-

52. 

Excluded because no eligible outcomes presented 

Colditz GA, Rosner BA, Speizer FE. Risk factors for breast 

cancer according to family history of breast cancer. For the 

Nurses' Health Study Research Group. J Natl Cancer Inst 

1996 Mar 20;88(6):365-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cole JC, Ownby DR, Havstad SL, et al. Family history, 

dust mite exposure in early childhood, and risk for pediatric 

atopy and asthma. J Allergy Clin Immunol 2004 

Jul;114(1):105-10. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Collins LC, Baer HJ, Tamimi RM, et al. The influence of 

family history on breast cancer risk in women with biopsyconfirmed benign breast disease: results from the Nurses' 

Health Study. Cancer 2006 Sep 15;107(6):1240-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cook D, Crowther M, Meade M, et al. Deep venous 

thrombosis in medical-surgical critically ill patients: 

Prevalence, incidence, and risk factors. Crit Care Med 

2005;33(7):1565-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cook LS, White JL, Stuart GCE, et al. The reliability of 

telephone interviews compared with in-person interviews 

using memory aids. Ann Epidemiol 2003;13(7):495-501. 

Excluded because no eligible outcomes presented 

Cooper GS, Wither J, McKenzie T, et al. The prevalence 

and accuracy of self-reported history of 11 autoimmune 

diseases. J Rheumatol 2008 Oct;35(10):2001-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Coppens M, Reijnders JH, Middeldorp S, et al. Testing for 

inherited thrombophilia does not reduce the recurrence of 

venous thrombosis. J Thromb Haemost 2008 

Sep;6(9):1474-7. 

Excluded because no eligible outcomes presented 

Cormier L, Reid K, Kwan L, et al. Screening behavior in 

brothers and sons of men with prostate cancer. J Urol 2003 

May;169(5):1715-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-13
Correa H, Campi-Azevedo AC, De Marco L, et al. Familial 

suicide behaviour: Association with probands suicide 

attempt characteristics and 5-HTTLPR polymorphism. Acta 

Psychiatr Scand 2004;110(6):459-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cosmi B, Legnani C, Bernardi F, et al. Value of family 

history in identifying women at risk of venous 

thromboembolism during oral contraception: observational 

study. Br Med J 2001 Apr 28;322(7293):1024-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cosmi B, Legnani C, Bernardi F, et al. Role of family 

history in identifying women with thrombophilia and 

higher risk of venous thromboembolism during oral 

contraception.[erratum appears in Arch Intern Med. 2003 

Aug 11-25;163(15):1778]. Arch Intern Med 2003 May 

12;163(9):1105-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Costa A, Rios M, Casamitjana R, et al. High prevalence of 

abnormal glucose tolerance and metabolic disturbances in 

first degree relatives of NIDDM patients. A study in 

Catalonia, a mediterranean community. Diabetes Res Clin 

Pract 1998;41(3):191-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Costanza ME, Luckmann R, Stoddard AM, et al. Applying 

a stage model of behavior change to colon cancer 

screening. Prev Med 2005;41(3-4):707-19. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cote ML, Kardia SL, Wenzlaff AS, et al. Risk of lung 

cancer among white and black relatives of individuals with 

early-onset lung cancer. JAMA 2005 Jun 22;293(24):3036-

42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cotter MP, Gern RW, Ho GY, et al. Role of family history 

and ethnicity on the mode and age of prostate cancer 

presentation. Prostate 2002 Mar 1;50(4):216-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cotterchio M, McKeown-Eyssen G, Sutherland H, et al. 

Ontario familial colon cancer registry: methods and firstyear response rates. Chronic Dis Can 2000;21(2):81-6. 

Excluded because no eligible outcomes presented 

Cottet V, Pariente A, Nalet B, et al. Low compliance with 

colonoscopic screening in first-degree relatives of patients 

with large adenomas. Aliment Pharmacol Ther 2006 Jul 

1;24(1):101-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cottet V, Pariente A, Nalet B, et al. Colonoscopic 

screening of first-degree relatives of patients with large 

adenomas: increased risk of colorectal tumors. 

Gastroenterology 2007 Oct;133(4):1086-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Couto E, Hemminki K. Estimates of heritable and 

environmental components of familial breast cancer using 

family history information. Br J Cancer 2007 Jun 

4;96(11):1740-2. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Couto E, Banks E, Reeves G, et al. Family history and 

breast cancer tumour characteristics in screened women. Int 

J Cancer 2008 Dec 15;123(12):2950-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Covelli MM. The relationship of blood pressure and 

cortisol reactivity to family history of hypertension of 

African American adolescents. J Cardiovasc Nurs 2006 

Sep;21(5):347-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cowan R, Meiser B, Giles GG, et al. The beliefs, and 

reported and intended behaviors of unaffected men in 

response to their family history of prostate cancer. Genet 

Med 2008 Jun;10(6):430-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-14
Cox B, Sneyd MJ, Paul C, et al. Risk factors for prostate 

cancer: A national case-control study. Int J Cancer 2006 

Oct 1;119(7):1690-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cox GF, Sleeper LA, Lowe AM, et al. Factors associated 

with establishing a causal diagnosis for children with 

cardiomyopathy. Pediatrics 2006 Oct;118(4):1519-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Crepeau AZ, Willoughby L, Pinsky B, et al. Accuracy of 

personal breast cancer risk estimation in cancer-free 

women during primary care visits. Women Health 

2008;47(2):113-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Crest AB, Aiello EJ, Anderson ML, et al. Varying levels of 

family history of breast cancer in relation to 

mammographic breast density (United States). Cancer 

Causes Control 2006 Aug;17(6):843-50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Criqui MH, Denenberg JO, Bergan J, et al. Risk factors for 

chronic venous disease: The San Diego Population Study. J 

Vasc Surg 2007;46(2):331-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Crispim D, Canani LH, Gross JL, et al. Familial history of 

type 2 diabetes in patients from Southern Brazil and its 

influence on the clinical characteristics of this disease. Arq 

Bras Endocrinol Metabol 2006 Oct;50(5):862-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Crispo A, D'Aiuto G, De Marco M, et al. Gail model risk 

factors: impact of adding an extended family history for 

breast cancer. Breast J 2008 May;14(3):221-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cui HB, Wang SH, Wang DQ, et al. Modified classic risk 

factors for coronary artery disease in Chinese Han 

population. Chin Med Sci J 2007;22(4):216-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cui J, Staples MP, Hopper JL, et al. Segregation analyses 

of 1,476 population-based Australian families affected by 

prostate cancer. Am J Hum Genet 2001 May;68(5):1207-

18. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cuijpers P, Smit F, Willemse G. Predicting the onset of 

major depression in subjects with subthreshold depression 

in primary care: A prospective study. Acta Psychiatr Scand 

2005;111(2):133-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cull A, Fry A, Rush R, et al. Cancer risk perceptions and 

distress among women attending a familial ovarian cancer 

clinic. Br J Cancer 2001 Mar 2;84(5):594-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Cummings SR, Lee JS, Lui LY, et al. Sex hormones, risk 

factors, and risk of estrogen receptor-positive breast cancer 

in older women: A long-term prospective study. Cancer 

Epidemiol Biomarkers Prev 2005;14(5):1047-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D'Avanzo B, La Vecchia C. Risk factors for male breast 

cancer. Br J Cancer 1995;71(6):1359-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dalal I, Binson I, Reifen R, et al. Food allergy is a matter 

of geography after all: Sesame as a major cause of severe 

IgE-mediated food allergic reactions among infants and 

young children in Israel. Allergy 2002;57(4):362-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dallongeville J, Grupposo MC, Cottel D, et al. Association 

between the metabolic syndrome and parental history of 

premature cardiovascular disease. Eur Heart J 2006 

Mar;27(6):722-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-15
and outcome criteria were met for the review questions in 

aggregate 

Damber L, Gronberg H, Damber J-E. Familial prostate 

cancer and possible associated malignancies: Nation- wide 

register cohort study in Sweden. Int J Cancer 

1998;78(3):293-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Damci T, Osar Z, Ilkova H. Higher blood pressure in 

normoalbuminuric type 1 diabetic patients with a familial 

history of type 2 diabetes. Diabetes Metab 2002 

Nov;28(5):417-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Davey RX, Hamblin PS. Selective versus universal 

screening for gestational diabetes mellitus: an evaluation of 

predictive risk factors. Med J Aust 2001 Feb 5;174(3):118-

21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Davids SL, Schapira MM, McAuliffe TL, et al. Predictors 

of pessimistic breast cancer risk perceptions in a primary 

care population. J Gen Intern Med 2004 Apr;19(4):310-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Davis LL, Frazier EC, Gaynes BN, et al. Are depressed 

outpatients with and without a family history of substance 

use disorder different? A baseline analysis of the STAR*D 

cohort. J Clin Psychiatry 2007 Dec;68(12):1931-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Davis S, Stewart S, Bloom J. Increasing the accuracy of 

perceived breast cancer risk: Results from a randomized 

trial with Cancer Information Service callers. Prev 

Medicine 2004 Jul;39(1):64-73. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Davis TME, Pramukkul P, Suputtamongkol Y, et al. 

Glucose tolerance in rural diabetic Thais, first-degree 

relatives and non-diabetic controls. Diabetes Res Clin Pract 

1995;27(3):171-80. 

Excluded because no eligible outcomes presented 

Dawson DA, Grant BF. Family history of alcoholism and 

gender: Their combined effects on DSM- IV alcohol 

dependence and major depression. J Stud Alcohol 

1997;59(1):97-106. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

De Bacquer D, De Backer G, Kornitzer M, et al. Parental 

history of premature coronary heart disease mortality and 

signs of ischemia on the resting electrocardiogram. J Am 

Coll Cardiol 1999 May;33(6):1491-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

de Bock GH, Jacobi CE, Seynaeve C, et al. A family 

history of breast cancer will not predict female early onset 

breast cancer in a population-based setting. BMC Cancer 

2008;8:203 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

de Jong AE, Vasen HF. The frequency of a positive family 

history for colorectal cancer: a population-based study in 

the Netherlands. Neth J Med 2006 Nov;64(10):367-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

de Jongh S, Lilien MR, Bakker HD, et al. Family history of 

cardiovascular events and endothelial dysfunction in 

children with familial hypercholesterolemia. 

Atherosclerosis 2002 Jul;163(1):193-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

De Oliveira MS, Serra E Silva, Papoila AL, et al. 

Assessment of global cardiovascular risk and risk factors in 

Portugal according to the SCORE model. J Public Health 

2008;16(5):361-7. 

Excluded because no eligible outcomes presented 

De Sario M, Di Domenicantonio R, Corbo G, et al. 

Characteristics of early transient, persistent, and late onset 

wheezers at 9 to 11 years of age. J Asthma 2006 

Oct;43(8):633-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

De Simone M, Verrotti A, Cappa M, et al. Lipoprotein (a) 

in childhood: correlations with family history of 

D-16
cardiovascular disease. J Endocrinol Invest 2003 

May;26(5):414-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

De Sutter J, De Bacquer D, Kotseva K, et al. Screening of 

family members of patients with premature coronary heart 

disease; results from the EUROASPIRE II family survey. 

Eur Heart J 2003 Feb;24(3):249-57. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

DeFaria YD, Freeman MW, Meigs JB, et al. Risk Factors 

for Coronary Artery Disease in Patients With Elevated 

High-Density Lipoprotein Cholesterol. Am J Cardiol 

2007;99(1):1-4. 

Excluded because no eligible outcomes presented 

Degli EE, Di Martino M, Sturani A, et al. Risk factors for 

uncontrolled hypertension in Italy. J Hum Hypertens 

2004;18(3):207-13. 

Excluded because family history not collected 

Dehlink E, Prandstetter C, Eiwegger T, et al. Increased 

prevalence of latex-sensitization among children with 

chronic renal failure. Allergy 2004;59(7):734-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dekker LRC, Bezzina CR, Henriques JPS, et al. Familial 

sudden death is an important risk factor for primary 

ventricular fibrillation: A case-control study in acute 

myocardial infarction patients. Circulation 

2006;114(11):1140-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

DelBello MP, Carlson GA, Tohen M, et al. Rates and 

Predictors of Developing a Manic or Hypomanic Episode 1 

to 2 Years Following a First Hospitalization for Major 

Depression with Psychotic Features. J Child Adolesc 

Psychopharmacol 2003;13(2):173-85. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Delpisheh A, Kelly Y, Rizwan S, et al. Salivary cotinine, 

doctor-diagnosed asthma and respiratory symptoms in 

primary schoolchildren. Matern Child Health J 2008 

Mar;12(2):188-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Deo SS, Gore SD, Deobagkar DN, et al. Study of 

inheritance of diabetes mellitus in Western Indian 

population by pedigree analysis. J Assoc Physicians India 

2006 Jun;54:441-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Derinoz O, Tumer L, Hasanoglu A, et al. Cholesterol 

screening in school children: is family history reliable to 

choose the ones to screen? Acta Paediatr 2007 

Dec;96(12):1794-8. 

Excluded because no eligible outcomes presented 

Devi G, Marder K, Schofield PW, et al. Validity of family 

history for the diagnosis of dementia among siblings of 

patients with late-onset Alzheimer's disease. Genet 

Epidemiol 1998;15(3):215-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Deyanov C, Vangelova K. Blood pressure response to 

exercise test and serum lipids in normotensive men with 

positive family history of hypertension. Cent Eur J Public 

Health 2006 Dec;14(4):186-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dezateux C, Stocks J, Dundas I, et al. Impaired airway 

function and wheezing in infancy: The influence of 

maternal smoking and a genetic predisposition to asthma. 

Am J Respir Crit Care Med 1999;159(2):403-10. 

Excluded because no eligible outcomes presented 

Di Cianni G, Volpe L, Lencioni C, et al. Prevalence and 

risk factors for gestational diabetes assessed by universal 

screening. Diabetes Res Clin Pract 2003;62(2):131-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dietrich JE, Hertweck SP, Perlman SE. Efficacy of family 

history in determining thrombophilia risk. J Pediatr 

Adolesc Gynecol 2007 Aug;20(4):221-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dilsaver SC, Akiskal HS, Akiskal KK, et al. Dose-response 

relationship between number of comorbid anxiety disorders 

in adolescent bipolar/unipolar disorders, and psychosis, 

D-17
suicidality, substance abuse and familiality. J Affect Disord 

2006;96(3):249-58. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dominguez FJ, Jones JL, Zabicki K, et al. Prevalence of 

hereditary breast/ovarian carcinoma risk in patients with a 

personal history of breast or ovarian carcinoma in a 

mammography population. Cancer 2005 Nov 

1;104(9):1849-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dominguez FJ, Lawrence C, Halpern EF, et al. Accuracy of 

self-reported personal history of cancer in an outpatient 

breast center. J Genet Couns 2007 Jun;16(3):341-5. 

Excluded because family history not collected 

Dong C, Hemminki K. Multiple primary cancers of the 

colon, breast and skin (melanoma) as models for polygenic 

cancers. Int J Cancer 2001 Jun 15;92(6):883-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dong C, Hemminki K. Modification of cancer risks in 

offspring by sibling and parental cancers from 2,112,616 

nuclear families. Int J Cancer 2001 Apr 1;92(1):144-50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Doughty M, Mehta R, Bruckman D, et al. Acute 

myocardial infarction in the young - The University of 

Michigan experience. Am Heart J 2002;143(1):56-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Douglas FS, O'Dair LC, Robinson M, et al. The accuracy 

of diagnoses as reported in families with cancer: a 

retrospective study. J Med Genet 1999 Apr;36(4):309-12. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dove-Edwin I, Sasieni P, Adams J, et al. Prevention of 

colorectal cancer by colonoscopic surveillance in 

individuals with a family history of colorectal cancer: 16 

Year, prospective, follow-up study. Br Med J 

2005;331(7524):1047-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Drake BF, Lathan CS, Okechukwu CA, et al. Racial 

differences in prostate cancer screening by family history. 

Ann Epidemiol 2008 Jul;18(7):579-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Drescher C, Holt SK, Andersen MR, et al. Reported 

ovarian cancer screening among a population-based sample 

in Washington State. Obstet Gynecol 2000;96(1):70-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Drossaert CC, Boer H, Seydel ER. Perceived risk, anxiety, 

mammogram uptake, and breast self-examination of 

women with a family history of breast cancer: the role of 

knowing to be at increased risk. Cancer Detect Prev 

1996;20(1):76-85. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Du Rocher Schudlich TD, Youngstrom EA, Calabrese JR, 

et al. The role of family functioning in bipolar disorder in 

families. J Abnorm Child Psychol 2008;36(6):849-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Duijm LEM, Guit GL, Zaat JOM. Mammographic 

surveillance of asymptomatic breast cancer relatives in 

general practice: rate of re-attendance and GP- and patientrelated barriers. Fam Pract 1997;14(6):450-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Dyck R, Klomp H, Tan LK, et al. A comparison of rates, 

risk factors, and outcomes of gestational diabetes between 

aboriginal and non-aboriginal women in the Saskatoon 

Health District. Diabetes Care 2002;25(3):487-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Easton DF, Matthews FE, Ford D, et al. Cancer mortality in 

relatives of women with ovarian cancer: the OPCS Study. 

Office of Population Censuses and Surveys. Int J Cancer 

1996 Jan 26;65(3):284-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-18
and outcome criteria were met for the review questions in 

aggregate 

Eaton CB, Bostom AG, Yanek L, et al. Family history and 

premature coronary heart disease. J Am Board Fam Pract 

1996 Sep;9(5):312-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Egan KM, Stampfer MJ, Rosner BA, et al. Risk factors for 

breast cancer in women with a breast cancer family history. 

Cancer Epidemiol Biomarkers Prev 1998 May;7(5):359-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Egawa N, Tu Y, Sanaka M, et al. Family history of diabetes 

and pancreatic cancer. Pancreas 2005 Jan;30(1):15-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ehlermann P, Weichenhan D, Zehelein J, et al. Adverse 

events in families with hypertrophic or dilated 

cardiomyopathy and mutations in the MYBPC3 gene. BMC 

Med Genet 2008;9:95 

Excluded because family history not collected 

Ehrmann DA, Kasza K, Azziz R, et al. Effects of race and 

family history of type 2 diabetes on metabolic status of 

women with polycystic ovary syndrome. J Clin Endocrinol 

Metab 2005 Jan;90(1):66-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Eisenmann JC, Wrede J, Heelan KA. Associations between 

adiposity, family history of CHD and blood pressure in 3-8 

year-old children. J Hum Hypertens 2005 Sep;19(9):675-

81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ekerljung L, Ronmark E, Larsson K, et al. No further 

increase of incidence of asthma: Incidence, remission and 

relapse of adult asthma in Sweden. Respir Med 

2008;102(12):1730-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Elbagir MN, Eltom MA, Elmahadi EMA, et al. A high 

prevalence of diabetes mellitus and impaired glucose 

tolerance in the Danagla community in Northern Sudan. 

Diabet Med 1998;15(2):164-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Eldon BJ, Jonsson E, Tomasson J, et al. Familial risk of 

prostate cancer in Iceland. BJU Int 2003 Dec;92(9):915-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Elis A, Pereg D, Tirosh A, et al. Family history of 

cardiovascular disease does not predict risk-reducing 

behavior. Eur J Cardiovasc Prev Rehabil 2008 

Jun;15(3):325-8. 

Excluded because no eligible outcomes presented 

Elit L, Esplen MJ, Butler K, et al. Quality of life and 

psychosexual adjustment after prophylactic oophorectomy 

for a family history of ovarian cancer. Fam Cancer 

2001;1(3-4):149-56. 

Excluded because family history not collected 

Emery J, Morris H, Goodchild R, et al. The GRAIDS Trial: 

a cluster randomised controlled trial of computer decision 

support for the management of familial cancer risk in 

primary care. Br J Cancer 2007 Aug 20;97(4):486-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Englert H, Small-McMahon J, Chambers P, et al. Familial 

risk estimation in systemic sclerosis. Aust N Z J Med 1999 

Feb;29(1):36-41. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Erasmus RT, Blanco BE, Okesina AB, et al. Importance of 

family history in type 2 black South African diabetic 

patients. Postgrad Med J 2001 May;77(907):323-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Erbey JR, Kuller LH, Becker DJ, et al. The association 

between a family history of type 2 diabetes and coronary 

artery disease in a type 1 diabetes population. Diabetes 

Care 1998 Apr;21(4):610-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-19
Erblich J, Bovbjerg DH, Valdimarsdottir HB. Looking 

forward and back: distress among women at familial risk 

for breast cancer. Ann Behav Med 2000;22(1):53-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Erblich J, Bovbjerg DH, Norman C, et al. It won't happen 

to me: lower perception of heart disease risk among women 

with family histories of breast cancer. Prev Med 2000 

Dec;31(6):714-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Etchegoyen GS, Ortiz D, Goya RG, et al. Assessment of 

cardiovascular risk factors in menopausal Argentinian 

women. Gerontology 1995;41(3):166-72. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Etzel CJ, Amos CI, Spitz MR. Risk for smoking-related 

cancer among relatives of lung cancer patients. Cancer Res 

2003 Dec 1;63(23):8531-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Evans DG, Walsh S, Jeacock J, et al. Incidence of 

hereditary non-polyposis colorectal cancer in a populationbased study of 1137 consecutive cases of colorectal cancer. 

Br J Surg 1997 Sep;84(9):1281-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Evans M, Palta M, Sadek M, et al. Associations between 

family history of asthma, bronchopulmonary dysplasia, and 

childhood asthma in very low birth weight children. Am J 

Epidemiol 1998 Sep 1;148(5):460-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ewertz M, Holmberg L, Tretli S, et al. Risk factors for 

male breast cancer--a case-control study from Scandinavia. 

Acta Oncol 2001;40(4):467-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Faheem M, Khurram M, Jafri IA, et al. Risk factors for 

breast cancer in patients treated at NORI Hospital, 

Islamabad. J Pak Med Assoc 2007;57(5):242-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fahim S, van Duijn CM, Baker FM, et al. A study of 

familial aggregation of depression, dementia and 

Parkinson's disease. Eur J Epidemiol 1998 Apr;14(3):233-

8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fang J, Foo SH, Fung C, et al. Stroke risk among Chinese 

immigrants in New York City. J Immigr Minor Health 

2006;8(4):387-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fedorowski A, Burri P, Hulthen L, et al. The metabolic 

syndrome and risk of myocardial infarction in familial 

hypertension (hypertension heredity in Malmo evaluation 

study). J Hypertens 2009 Jan;27(1):109-17. 

Excluded because family history not collected 

Fernandez-Egea E, Miller B, Bernardo M, et al. Parental 

history of type 2 diabetes in patients with nonaffective 

psychosis. Schizophr Res 2008 Jan;98(1-3):302-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fernandez E, La Vecchia C, Talamini R, et al. Joint effects 

of family history and adult life dietary risk factors on 

colorectal cancer risk. Epidemiology 2002 May;13(3):360-

3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fernandez E, Gallus S, La Vecchia C, et al. Family history 

and environmental risk factors for colon cancer. Cancer 

Epidemiol Biomarkers Prev 2004 Apr;13(4):658-61. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fernandez E, Gallus S, La Vecchia C, et al. Family history 

and environmental risk factors for colon cancer. Cancer 

Epidemiol Biomarkers Prev 2004;13(4):658-61. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-20
Ferrante JM, Ohman-Strickland P, Hahn KA, et al. Selfreport versus medical records for assessing cancerpreventive services delivery. Cancer Epidemiol Biomarkers 

Prev 2008;17(11):2987-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ferrari M, Tardivo S, Zanolin ME, et al. Serious childhood 

respiratory infections and asthma in adult life. A population 

based study. Ann Allergy Asthma Immunol 

1999;83(5):391-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fesharakinia A, Kazemi T, Zarban A, et al. Comparison of 

Lipoprotein (a) and Apolipoproteins in children with and 

without familial history of premature coronary artery 

disease. Iran J Pediatr 2008;18(2):159-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Figueiredo JC, Ennis M, Knight JA, et al. Influence of 

young age at diagnosis and family history of breast or 

ovarian cancer on breast cancer outcomes in a populationbased cohort study. Breast Cancer Res Treat 2007 

Sep;105(1):69-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Filion E, Taussky D, Bahary JP, et al. Higher frequency of 

familial clustering of prostate cancer in French-Canadian 

men. J Urol 2007;178(4:Pt 1):1265-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Finney Rutten LJ, Iannotti RJ. Health beliefs, salience of 

breast cancer family history, and involvement with breast 

cancer issues: adherence to annual mammography 

screening recommendations. Cancer Detect Prev 

2003;27(5):353-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Finney LJ, Iannotti RJ. The impact of family history of 

breast cancer on women's health beliefs, salience of breast 

cancer family history, and degree of involvement in breast 

cancer issues. Women Health 2001;33(3-4):15-28. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fioretti F, Tavani A, Bosetti C, et al. Risk factors for breast 

cancer in nulliparous women. Br J Cancer 1999;79(11-

12):1923-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fisher TJ, Kirk J, Hopper JL, et al. A simple tool for 

identifying unaffected women at a moderately increased or 

potentially high risk of breast cancer based on their family 

history. Breast 2003 Apr;12(2):120-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Flint EP, Hays JC, Krishnan KRR, et al. Suicidal behaviors 

in depressed men with a family history of suicide: effects of 

psychosocial factors and age. Aging Ment Health 1998 

Nov;2(4):286-99. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Flossmann E, Rothwell PM. Family history of stroke in 

patients with transient ischemic attack in relation to 

hypertension and other intermediate phenotypes. Stroke 

2005 Apr;36(4):830-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ford BM, Evans JS, Stoffel EM, et al. Factors associated 

with enrollment in cancer genetics research. Cancer 

Epidemiol Biomarkers Prev 2006;15(7):1355-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fornage M, Lopez DS, Roseman JM, et al. Parental history 

of stroke and myocardial infarction predicts coronary artery 

calcification: The Coronary Artery Risk Development in 

Young Adults (CARDIA) study. Eur J Cardiovasc Prev 

Rehabil 2004 Oct;11(5):421-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fornasarig M, Campagnutta E, Talamini R, et al. Risk 

factors for endometrial cancer according to familial 

susceptibility. Int J Cancer 1998 Jul 3;77(1):29-32. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-21
and outcome criteria were met for the review questions in 

aggregate 

Fox ER, Benjamin EJ, Sarpong DF, et al. Epidemiology, 

heritability, and genetic linkage of C-reactive protein in 

African Americans (from the Jackson Heart Study). Am J 

Cardiol 2008 Oct 1;102(7):835-41. 

Excluded because family history not collected 

Fraser GE, Shavlik D. Risk factors, lifetime risk, and age at 

onset of breast cancer. Ann Epidemiol 1997 Aug;7(6):375-

82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Freedman AN, Slattery ML, Ballard-Barbash R, et al. 

Colorectal cancer risk prediction tool for white men and 

women without known susceptibility. J Clin Oncol 2009 

Feb 10;27(5):686-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Frezzo TM, Rubinstein WS, Dunham D, et al. The genetic 

family history as a risk assessment tool in internal 

medicine. Genet Med 2003;5(2):84-91. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Frich JC, Ose L, Malterud K, et al. Perceived vulnerability 

to heart disease in patients with familial 

hypercholesterolemia: a qualitative interview study. Ann 

Fam Med 2006 May;4(3):198-204. 

Excluded because not an eligible study design 

Friedlander Y, Siscovick DS, Weinmann S, et al. Family 

history as a risk factor for primary cardiac arrest. 

Circulation 1998 Jan 20;97(2):155-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Friedlander Y, Arbogast P, Schwartz SM, et al. Family 

history as a risk factor for early onset myocardial infarction 

in young women. Atherosclerosis 2001 May;156(1):201-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Friedlander Y, Siscovick DS, Arbogast P, et al. Sudden 

death and myocardial infarction in first degree relatives as 

predictors of primary cardiac arrest. Atherosclerosis 2002 

May;162(1):211-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Friedman LC, Webb JA, Everett TE. Psychosocial and 

medical predictors of colorectal cancer screening among 

low-income medical outpatients. J Cancer Educ 

2004;19(3):180-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Friedman S. Sharing family history. CURE: Cancer 

Updates, Research & Education 2003;2(3):58 

Excluded because not an eligible study design 

Fry A, Rush R, Busby-Earle C, et al. Deciding about 

prophylactic oophorectomy: What is important to women at 

increased risk of ovarian cancer? Prev Med 2001 

Dec;33(6):578-85. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fu C-C, Chen J-D, Chern TPS, et al. The relationship 

between parental medical histories and coronary risk 

factors in adult progeny of type 2 diabetics. Tzu Chi 

Medical Journal 2002;14(1):7-12. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fuchs CS, Willett WC, Colditz GA, et al. The influence of 

folate and multivitamin use on the familial risk of colon 

cancer in women. Cancer Epidemiol Biomarkers Prev 2002 

Mar;11(3):227-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fujisawa T, Ikegami H, Kawaguchi Y, et al. Common 

genetic basis between type 1 and type 2 diabetes mellitus 

indicated by interview-based assessment of family history. 

Diabetes Res Clin Pract 2004 Dec;66(Suppl 1):S91-S915 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Fujiwara S, Suyama A, Cologne JB, et al. Prevalence of 

adult-onset multifactorial disease among offspring of 

atomic bomb survivors. Radiat Res 2008 Oct;170(4):451-7. 

Excluded because family history not collected 

Fukiwake N, Furusyo N, Takeoka H, et al. Association 

factors for atopic dermatitis in nursery school children in 

Ishigaki Islands - Kyushu University Ishigaki atopic 

dermatitis study (KIDS). Eur J Dermatol 2008;18(5):571-4. 

D-22
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gaff CL, Aragona C, MacInnis RJ, et al. Accuracy and 

completeness in reporting family history of prostate cancer 

by unaffected men. Urology 2004 Jun;63(6):1111-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gaga M, Papageorgiou N, Yiourgioti G, et al. Risk factors 

and characteristics associated with severe and difficult to 

treat asthma phenotype: An analysis of the ENFUMOSA 

group of patients based on the ECRHS questionnaire. Clin 

Exp Allergy 2005;35(7):954-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gallus S, Foschi R, Talamini R, et al. Risk Factors for 

Prostate Cancer in Men Aged Less Than 60 Years: A CaseControl Study from Italy. Urology 2007;70(6):1121-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ganguly SS, Dutta PK, Tilak VW. Evaluation of some risk 

factors for ischaemic heart disease under a matched pairs 

case-control design. Indian J Med Res 1997 Jun;105:278-

82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Garbers V, Toniolo PG, Taioli E. Changes in self-reported 

family history of breast cancer with change in case-control 

status. Eur J Epidemiol 2001;17(6):517-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Garcia K, Eisenmann JC, Bartee RT. Does a family history 

of coronary heart disease modify the relationship between 

physical activity and blood pressure in young adults? Eur J 

Cardiovasc Prev Rehabil 2004 Jun;11(3):201-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gazit V, Tasher D, Hanukoglu A, et al. Atopy in children 

and adolescents with insulin-dependent diabetes mellitus. 

Isr Med Assoc J 2008 Dec;10(12):858-61. 

Excluded because no eligible outcomes presented 

George S, Berth-Jones J, Graham-Brown RA. A possible 

explanation for the increased referral of atopic dermatitis 

from the Asian community in Leicester. Br J Dermatol 

1997 Apr;136(4):494-7. 

Excluded because no eligible outcomes presented 

Georgy V, Fahim HI, El Gaafary M, et al. Prevalence and 

socioeconomic associations of asthma and allergic rhinitis 

in northern Africa. Eur Respir J 2006;28(4):756-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ghadirian P, Howe GR, Hislop TG, et al. Family history of 

prostate cancer: a multi-center case-control study in 

Canada. Int J Cancer 1997 Mar 17;70(6):679-81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ghadirian P, Lacroix A, Perret C, et al. Sociodemographic 

characteristics, smoking, medical and family history, and 

breast cancer. Cancer Detect Prev 1998;22(6):485-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gidron Y, Berger R, Lugasi B, et al. Interactions of 

psychological factors and family history in relation to 

coronary artery disease. Coron Artery Dis 2002 

Jun;13(4):205-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gil F, Mendez I, Sirgo A, et al. Perception of breast cancer 

risk and surveillance behaviours of women with family 

history of breast cancer: a brief report on a Spanish cohort. 

Psychooncology 2003 Dec;12(8):821-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gilani GM, Kamal S. Risk factors for breast cancer in 

Pakistani women aged less than 45 years. Ann Hum Biol 

2004 Jul;31(4):398-407. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gilbar O, Borovik R. How daughters of women with breast 

cancer cope with the threat of the illness. Behav Med 

1998;24(3):115-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-23
and outcome criteria were met for the review questions in 

aggregate 

Gilliam LK, Liese AD, Bloch CA, et al. Family history of 

diabetes, autoimmunity, and risk factors for cardiovascular 

disease among children with diabetes in the SEARCH for 

Diabetes in Youth Study. Pediatr Diabetes 2007 

Dec;8(6):354-61. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gilliland FD, Larson M, Chao A. Risk factor information 

found in medical records of lung and prostate cancer cases, 

New Mexico Tumor Registry (United States). Cancer 

Causes Control 1997 Jul;8(4):598-604. 

Excluded because no eligible outcomes presented 

Gilvarry CM, Sham PC, Jones PB, et al. Family history of 

autoimmune diseases in psychosis. Schizophr Res 1996 

Mar;19(1):33-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Glans F, Elgzyri T, Shaat N, et al. Immigrants from the 

Middle-East have a different form of Type 2 diabetes 

compared with Swedish patients. Diabet Med 2008 

Mar;25(3):303-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Glanz K, Grove J, Le Marchand L, et al. Underreporting of 

family history of colon cancer: correlates and implications. 

Cancer Epidemiol Biomarkers Prev 1999 Jul;8(7):635-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Glaser SL, Chang ET, Horning SJ, et al. Understanding the 

validity of self-reported positive family history of 

lymphoma in extended families to facilitate genetic 

epidemiology and clinical practice. Leuk Lymphoma 2007 

Jun;48(6):1110-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Glover FE, Jr., Coffey DS, Douglas LL, et al. Familial 

study of prostate cancer in Jamaica. Urology 1998 

Sep;52(3):441-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Glowinska B, Urban M, Koput A. Cardiovascular risk 

factors in children with obesity, hypertension and diabetes: 

lipoprotein(a) levels and body mass index correlate with 

family history of cardiovascular disease. Eur J Pediatr 2002 

Oct;161(10):511-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Glumer C, Carstensen B, Sandbaek A, et al. A Danish 

Diabetes Risk Scope for Targeted Screening: The Inter99 

study. Diabetes Care 2004;27(3):727-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gnanalingham MG, Manns JJ. Patient awareness of genetic 

and environmental risk factors in non-insulin-dependent 

diabetes mellitus--relevance to first-degree relatives. Diabet 

Med 1997 Aug;14(8):660-2. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Godard B, Foulkes WD, Provencher D, et al. Risk factors 

for familial and sporadic ovarian cancer among French 

Canadians: a case-control study. Am J Obstet Gynecol 

1998 Aug;179(2):403-10. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gokcel A, Ozsahin AK, Sezgin N, et al. High Prevalence of 

Diabetes in Adana, a Southern Province of Turkey. 

Diabetes Care 2003;26(11):3031-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Goldstein IB, Shapiro D, Guthrie D. Ambulatory Blood 

Pressure and Family History of Hypertension in Healthy 

Men and Women. Am J Hypertens 2006;19(5):486-91. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Goldstein IB, Shapiro D, Weiss RE. How family history 

and risk factors for hypertension relate to ambulatory blood 

pressure in healthy adults. J Hypertens 2008 Feb;26(2):276-

83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-24
Gomez JE, Lantry BR, Saathoff KN. Current use of 

adequate preparticipation history forms for heart disease 

screening of high school athletes. Arch Pediatr Adolesc 

Med 1999 Jul;153(7):723-6. 

Excluded because not an eligible population 

Gong L, Kao WH, Brancati FL, et al. Association between 

parental history of type 2 diabetes and glycemic control in 

urban African Americans. Diabetes Care 2008 

Sep;31(9):1773-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gonzalez-Ortiz M, Martinez-Abundis E, Cardona-Munoz 

EG, et al. Metabolic profile and insulin sensitivity in 

healthy young Mexicans with a strong family history of 

non-insulin-dependent diabetes mellitus in the paternal 

branch. Arch Med Res 1997;28(3):421-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gonzalez-Ortiz M, Martinez-Abundis E. Maternal effect of 

Type 2 diabetes mellitus on insulin sensitivity and 

metabolic profile in healthy young Mexicans. Diabetes 

Nutr Metab 1999 Feb;12(1):32-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Goodwin RD, Wickramaratne P, Nomura Y, et al. Familial 

depression and respiratory illness in children. Arch Pediatr 

Adolesc Med 2007 May;161(5):487-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gorlova OY, Zhang Y, Schabath MB, et al. Never smokers 

and lung cancer risk: a case-control study of 

epidemiological factors. Int J Cancer 2006 Apr 

1;118(7):1798-804. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gorlova OY, Weng SF, Zhang Y, et al. Aggregation of 

cancer among relatives of never-smoking lung cancer 

patients. Int J Cancer 2007 Jul 1;121(1):111-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grabrick DM, Hartmann LC, Cerhan JR, et al. Risk of 

breast cancer with oral contraceptive use in women with a 

family history of breast cancer. JAMA 2000 Oct 

11;284(14):1791-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gramling R, Anthony D, Lowery J, et al. Association 

between screening family medical history in general 

medical care and lower burden of cancer worry among 

women with a close family history of breast cancer. Genet 

Med 2005 Nov;7(9):640-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gramling R, Anthony D, Simmons E, et al. Self-rated 

breast cancer risk among women reporting a first-degree 

family history of breast cancer on office screening 

questionnaires in routine medical care: the role of 

physician-delivered risk feedback. Genet Med 2006 

Oct;8(10):658-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grandi AM, Zanzi P, Broggi R, et al. Longitudinal changes 

of insulin sensitivity in essential hypertension: Influence of 

blood pressure control and familial predisposition to 

hypertension. J Clin Endocrinol Metab 2001;86(7):3027-

31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Granstrom C, Sundquist J, Hemminki K. Population 

attributable fractions for ovarian cancer in Swedish women 

by morphological type. Br J Cancer 2008;98(1):199-205. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grant BF, Dawson DA, Stinson FS, et al. The Alcohol Use 

Disorder and Associated Disabilities Interview ScheduleIV (AUDADIS-IV): Reliability of alcohol consumption, 

tobacco use, family history of depression and psychiatric 

diagnostic modules in a general population sample. Drug 

Alcohol Depend 2003;71(1):7-16. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grasbeck A, Horstmann V, Nilsson K, et al. Dementia in 

first-degree relatives of patients with frontotemporal 

dementia: a family history study. Dement Geriatr Cogn 

Disord 2005;19(2-3):145-53. 

D-25
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grassi M, Bugiani M, De Marco R. Investigating indicators 

and determinants of asthma in young adults. Eur J 

Epidemiol 2006;21(11):831-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gravely-Witte S, Stewart DE, Suskin N, et al. 

Cardiologists' charting varied by risk factor, and was often 

discordant with patient report. J Clin Epidemiol 

2008;61(10):1073-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Greenlund KJ, Valdez R, Bao W, et al. Verification of 

parental history of coronary artery disease and associations 

with adult offspring risk factors in a community sample: 

the Bogalusa Heart Study. Am J Med Sci 1997 

Apr;313(4):220-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Greggi S, Parazzini F, Paratore MP, et al. Risk factors for 

ovarian cancer in central Italy. Gynecol Oncol 2000 

Oct;79(1):50-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Gregory H, Wordsworth S, Gibbons B, et al. Risk 

estimation for familial breast cancer: improving the system 

of counselling. Eur J Hum Genet 2007 Nov;15(11):1139-

44. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Griffin SJ, Little PS, Hales CN, et al. Diabetes risk score: 

Towards earlier detection or type 2 diabetes in general 

practice. Diabetes Metab Res Rev 2000;16(3):164-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grigoroiu-Serbanescu M, Nothen MM, Ohlraun S, et al. 

Family history influences age of onset in bipolar I disorder 

in females but not in males. Am J Med Genet B 

Neuropsychiatr Genet 2005;133(1):6-11. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grill V, Persson G, Carlsson S, et al. Family history of 

diabetes in middle-aged Swedish men is a gender unrelated 

factor which associates with insulinopenia in newly 

diagnosed diabetic subjects. Diabetologia 1999 

Jan;42(1):15-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Groop L, Forsblom C, Lehtovirta M, et al. Metabolic 

consequences of a family history of NIDDM (the Botnia 

study): evidence for sex-specific parental effects. Diabetes 

1996 Nov;45(11):1585-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grosz A, Toth E, Peter I. A 10-year follow-up of ischemic 

heart disease risk factors in military pilots. Mil Med 

2007;172(2):214-9. 

Excluded because no eligible outcomes presented 

Grotto I, Huerta M, Kark JD, et al. Relation of parental 

history of coronary heart disease to obesity in young adults. 

Int J Obes Relat Metab Disord 2003 Mar;27(3):362-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grover S, Stoffel EM, Bussone L, et al. Physician 

assessment of family cancer history and referral for genetic 

evaluation in colorectal cancer patients. Clin Gastroenterol 

Hepatol 2004 Sep;2(9):813-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Grunberg H, Thetloff M. The cardiovascular risk factor 

profile of Estonian school children. Acta Paediatr 

1998;87(1):37-42. 

Excluded because no eligible outcomes presented 

Grunig E, Tasman JA, Kucherer H, et al. Frequency and 

phenotypes of familial dilated cardiomyopathy. J Am Coll 

Cardiol 1998 Jan;31(1):186-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Guerrer-Romer F, Rodriguez-Moran M, Gonzalez-Ortiz M, 

et al. Insulin action and secretion in healthy HispanicD-26
Mexican first-degree relatives of subjects with type 2 

diabetes. J Endocrinol Invest 2001 Sep;24(8):580-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Guerrero-Romero F, Rodriguez-Moran M. Prevalence of 

dyslipidemia in non-obese prepubertal children and its 

association with family history of diabetes, high blood 

pressure, and obesity. Arch Med Res 2006 

Nov;37(8):1015-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Guillem JG, Bastar AL, Ng J, et al. Clustering of colorectal 

cancer in families of probands under 40 years of age. Dis 

Colon Rectum 1996 Sep;39(9):1004-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Guirguis-Blake J. Cancer genetic risk assessment for 

individuals at risk of familial breast cancer. Am Fam 

Physician 2008;77(4):450-2. 

Excluded because not an eligible study design 

Gunaid AA, El Khally FMY, Hassan NAGM, et al. 

Demographic and clinical features of diabetes mellitus in 

1095 Yemeni patients. Ann Saudi Med 1997;17(4):402-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hadaegh F, Bozorgmanesh MR, Ghasemi A, et al. High 

prevalence of undiagnosed diabetes and abnormal glucose 

tolerance in the Iranian urban population: Tehran Lipid and 

Glucose Study. BMC Public Health 2008;8:176 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hadfield SG, Horara S, Starr BJ, et al. Are patients with 

familial hypercholesterolaemia well managed in lipid 

clinics? An audit of eleven clinics from the Department of 

Health Familial Hypercholesterolaemia Cascade Testing 

project. Ann Clin Biochem 2008;45(2):199-205. 

Excluded because no eligible outcomes presented 

Haines L, Wan KC, Lynn R, et al. Rising incidence of type 

2 diabetes in children in the U.K. Diabetes Care 

2007;30(5):1097-101. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Halapy EE, Chiarelli AM, Klar N, et al. Breast screening 

outcomes in women with and without a family history of 

breast and/or ovarian cancer. J Med Screen 2004;11(1):32-

8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hall IJ, Burke W, Coughlin S, et al. Population-based 

estimates of the prevalence of family history of cancer 

among women. Community Genet 2001;4(3):134-42. 

Excluded because no eligible outcomes presented 

Hall NR, Bishop DT, Stephenson BM, et al. Hereditary 

susceptibility to colorectal cancer. Relatives of early onset 

cases are particularly at risk. Dis Colon Rectum 1996 

Jul;39(7):739-43. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hallowell N, Murton F, Statham H, et al. Women's need for 

information before attending genetic counselling for 

familial breast or ovarian cancer: a questionnaire, 

interview, and observational study. BMJ 1997 Jan 

25;314(7076):281-3. 

Excluded because no eligible outcomes presented 

Halmerbauer G, Gartner C, Schierl M, et al. Study on the 

Prevention of Allergy in Children in Europe (SPACE): 

Allergic sensitization at 1 year of age in a controlled trial of 

allergen avoidance from birth. Pediatr Allergy Immunol 

2003;14(1):10-7. 

Excluded because no eligible outcomes presented 

Hamid ZA, Kariem KA, Rashid MS, et al. Prevalence of 

Type 2 diabetes mellitus and impaired glucose tolerance in 

the Kashmir Valley of the Indian subcontinent. Diabetes 

Res Clin Pract 2000;47(2):135-46. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Harada K, Karube Y, Saruhara H, et al. Workplace 

hypertension is associated with obesity and family history 

of hypertension. Hypertens Res 2006 Dec;29(12):969-76. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Haraguchi S, Koizumi K, Hioki M, et al. Hereditary factors 

in multiple primary malignancies associated with lung 

cancer. Surg Today 2007;37(5):375-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-27
Harder T, Franke K, Kohlhoff R, et al. Maternal and 

paternal family history of diabetes in women with 

gestational diabetes or insulin-dependent diabetes mellitus 

type I. Gynecol Obstet Invest 2001;51(3):160-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Harpaz D, Behar S, Rozenman Y, et al. Family history of 

coronary artery disease and prognosis after first acute 

myocardial infarction in a national survey. Cardiology 

2004;102(3):140-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Harrop J, Chinn S, Verlato G, et al. Eczema, atopy and 

allergen exposure in adults: A population-based study. Clin 

Exp Allergy 2007;37(4):526-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hartmann LC, Sellers TA, Frost MH, et al. Benign breast 

disease and the risk of breast cancer. N Engl J Med 

2005;353(3):229-37. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Harwood DG, Barker WW, Ownby RL, et al. Family 

history of dementia and current depression in nondemented 

community-dwelling older adults. J Geriatr Psychiatry 

Neurol 2000;13(2):65-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hauner H, Hanisch J, Bramlage P, et al. Prevalence of 

undiagnosed type-2-diabetes mellitus and impaired fasting 

glucose in German primary care: Data from the German 

metabolic and cardiovascular risk project (GEMCAS). Exp 

Clin Endocrinol Diabetes 2008;116(1):18-25. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hawe E, Talmud PJ, Miller GJ, et al. Family history is a 

coronary heart disease risk factor in the Second Northwick 

Park Heart Study. Ann Hum Genet 2003 Mar;67(Pt:2):97-

106. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hayes RB, Liff JM, Pottern LM, et al. Prostate cancer risk 

in U.S. blacks and whites with a family history of cancer. 

Int J Cancer 1995 Jan 27;60(3):361-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hebert-Croteau N, Goggin P, Kishchuk N. Estimation of 

breast cancer risk by women aged 40 and over: A 

population-based study. Can J Public Health 

1997;88(6):392-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Heidari Z, Mahmoudzadeh-Sagheb HR, Sakhavar N. Breast 

cancer screening knowledge and practice among women in 

southeast of Iran. Acta Med Iran 2008;46(4):321-8. 

Excluded because no eligible outcomes presented 

Hemminki K, Vaittinen P. Effect of paternal and maternal 

cancer on cancer in the offspring: A population-based 

study. Cancer Epidemiol Biomarkers Prev 1997;6(12):993-

7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Vaittinen P. Familial risks in in situ cancers 

from the Family-Cancer Database. Cancer Epidemiol 

Biomarkers Prev 1998 Oct;7(10):865-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Granstrom C, Czene K. Attributable risks for 

familial breast cancer by proband status and morphology: a 

nationwide epidemiologic study from Sweden. Int J Cancer 

2002 Jul 10;100(2):214-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Czene K. Age specific and attributable risks 

of familial prostate carcinoma from the family-cancer 

database. Cancer 2002 Sep 15;95(6):1346-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Chen B. Familial association of colorectal 

adenocarcinoma with cancers at other sites. Eur J Cancer 

2004 Nov;40(16):2480-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-28
and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Granstrom C. Familial clustering of ovarian 

and endometrial cancers. Eur J Cancer 2004 Jan;40(1):90-

5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Chen B. Familial association of prostate 

cancer with other cancers in the Swedish Family-Cancer 

Database. Prostate 2005 Oct 1;65(2):188-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Li X. Familial risk for lung cancer by 

histology and age of onset: evidence for recessive 

inheritance. Exp Lung Res 2005 Mar;31(2):205-15. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Ji J, Forsti A. Risks for familial and 

contralateral breast cancer interact multiplicatively and 

cause a high risk. Cancer Res 2007 Feb 1;67(3):868-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Forsti A, Sundquist J, et al. Risk of familial 

breast cancer is not increased after pregnancy. Breast 

Cancer Res Treat 2008;108(3):417-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hemminki K, Zhang H, Sundquist J, et al. Modification of 

risk for subsequent cancer after female breast cancer by a 

family history of breast cancer. Breast Cancer Res Treat 

2008;111(1):165-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Henderson BJ, Tyndel S, Brain K, et al. Factors associated 

with breast cancer-specific distress in younger women 

participating in a family history mammography screening 

programme. Psychooncology 2008 Jan;17(1):74-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hersberger KE, Botomino A, Mancini M, et al. Sequential 

screening for diabetes--evaluation of a campaign in Swiss 

community pharmacies. Pharm World Sci 2006 

Jun;28(3):171-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hershey CO, Grant BJ. Controlled trial of a patientcompleted history questionnaire: effects on quality of 

documentation and patient and physician satisfaction. Am J 

Med Qual 2002 Jul;17(4):126-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Higgins PS, Wakefield D, Cloutier MM. Risk factors for 

asthma and asthma severity in nonurban children in 

Connecticut. Chest 2005;128(6):3846-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hijazi N, Abalkhail B, Seaton A. Diet and childhood 

asthma in a society in transition: A study in urban and rural 

Saudi Arabia. Thorax 2000;55(9):775-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hill DA, Preston-Martin S, Ross RK, et al. Medical 

radiation, family history of cancer, and benign breast 

disease in relation to breast cancer risk in young women, 

USA. Cancer Causes Control 2002 Oct;13(8):711-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hines LM, Risendal B, Slattery ML, et al. Differences in 

estrogen receptor subtype according to family history of 

breast cancer among Hispanic, but not non-Hispanic White 

women. Cancer Epidemiol Biomarkers Prev 2008 

Oct;17(10):2700-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hippisley-Cox J, Coupland C, Vinogradova Y, et al. 

Derivation and validation of QRISK, a new cardiovascular 

disease risk score for the United Kingdom: prospective 

open cohort study. BMJ 2007 Jul 21;335(7611):136 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-29
Hippisley-Cox J, Coupland C, Vinogradova Y, et al. 

Predicting cardiovascular risk in England and Wales: 

prospective derivation and validation of QRISK2. BMJ 

2008 Jun 28;336(7659):1475-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hiripi E, Bermejo JL, Sundquist J, et al. Association of 

colorectal adenoma with other malignancies in Swedish 

families. Br J Cancer 2008 Mar 11;98(5):997-1000. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hirose K, Tajima K, Hamajima N, et al. A large-scale, 

hospital-based case-control study of risk factors of breast 

cancer according to menopausal status. Jpn J Cancer Res 

1995 Feb;86(2):146-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hirose K, Tajima K, Hamajima N, et al. Impact of family 

history on the risk of breast cancer among the Japanese. Jpn 

J Cancer Res 1997 Dec;88(12):1130-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hirose K, Tajima K, Hamajima N, et al. Association of 

family history and other risk factors with breast cancer risk 

among Japanese premenopausal and postmenopausal 

women. Cancer Causes Control 2001 May;12(4):349-58. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hlavaty T, Lukac L, Huorka M, et al. Positive family 

history promotes participation in colorectal cancer 

screening. Bratisl Lek Listy 2005;106(10):318-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hollman G, Olsson AG, Ek AC. Familial 

hypercholesterolaemia and quality of life in family 

members. Prev Med 2003 May;36(5):569-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hopkins PN, Ellison RC, Province MA, et al. Association 

of Coronary Artery Calcified Plaque With Clinical 

Coronary Heart Disease in the National Heart, Lung, and 

Blood Institute's Family Heart Study. Am J Cardiol 

2006;97(11):1564-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hornsby-Lewis L. Family history increases the risk of 

colorectal cancer. Gastroenterology 1995 Sep;109(3):1015-

7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

House W, Sharp D, Sheridan E. Identifying and screening 

patients at high risk of colorectal cancer in general practice. 

J Med Screen 1999;6(4):205-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hu G, Tian H. A comparison of dietary and non-dietary 

factors of hypertension and normal blood pressure in a 

Chinese population. J Hum Hypertens 2001;15(7):487-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Huang D, Guan P, Shi H, et al. Reliability and accuracy of 

interview data in non-smoking female lung cancer casecontrol study. J Exp Clin Cancer Res 2008;27(1): 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Huang JL, Chen CC, Kuo ML, et al. Exposure to a high 

concentration of mite allergen in early infancy is a risk 

factor for developing atopic dermatitis: a 3-year follow-up 

study. Pediatr Allergy Immunol 2001 Feb;12(1):11-6. 

Excluded because no eligible outcomes presented 

Hughes KS, Roche C, Campbell CT, et al. Prevalence of 

family history of breast and ovarian cancer in a single 

primary care practice using a self-administered 

questionnaire. Breast J 2003 Jan;9(1):19-25. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hunt KJ, Heiss G, Sholinsky PD, et al. Familial history of 

metabolic disorders and the multiple metabolic syndrome: 

the NHLBI family heart study. Genet Epidemiol 2000 

Dec;19(4):395-409. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-30
Hunter A, Vimplis S, Sharma A, et al. To determine 

whether first-degree male relatives of women with 

polycystic ovary syndrome are at higher risk of developing 

cardiovascular disease and type II diabetes mellitus. J 

Obstet Gynaecol 2007 Aug;27(6):591-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hurrell C, Wietlisbach V, Jotterand V, et al. High 

prevalence of major cardiovascular risk factors in firstdegree relatives of individuals with familial premature 

coronary artery disease--the GENECARD project. 

Atherosclerosis 2007 Sep;194(1):253-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Husseini A, Abdul-Rahim H, Awartani F, et al. Type 2 

diabetes mellitus, impaired glucose tolerance and 

associated factors in a rural palestinian village. Diabet Med 

2000;17(10):746-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Husseini A, Abdul-Rahim H, Giacaman R, et al. Selected 

factors associated with diabetes mellitus in a rural 

Palestinian community. Med Sci Monit 2003;9(5):CR181-

CR185 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Hyland F, Kinmonth AL, Marteau TM, et al. Raising 

concerns about family history of breast cancer in primary 

care consultations: prospective, population based study. 

Women's Concerns Study Group. BMJ 2001 Jan 

6;322(7277):27-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Imperiale TF, Kahi CJ, Stuart JS, et al. Risk factors for 

advanced sporadic colorectal neoplasia in persons younger 

than age 50. Cancer Detect Prev 2008;32(1):33-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Iqbal Hydrie MZ, Basit A, Ahmedani MY, et al. 

Comparison of risk factors for diabetes in children of 

different socioeconomic status. J Coll Physicians Surg Pak 

2005;15(2):74-7. 

Excluded because no eligible outcomes presented 

Iqbal SP, Dodani S, Qureshi R. Risk factors and behaviours 

for coronary artery disease (CAD) among ambulatory 

Pakistanis. J Pak Med Assoc 2004;54(5):261-6. 

Excluded because no eligible outcomes presented 

Irving RR, Mills JL, Choo-Kang EG, et al. The burden of 

gestational diabetes mellitus in Jamaican women with a 

family history of autosomal dominant type 2 diabetes. Rev 

Panam Salud Publica 2008 Feb;23(2):85-91. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Irving RR, Mills JL, Choo-Kang EG, et al. Diabetes and 

psychological co-morbidity in children with a family 

history of early-onset type 2 diabetes. Int J Psychol 2008 

Dec;43(6):937-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ishikawa M, Pruneda ML, Adams-Huet B, et al. Obesityindependent hyperinsulinemia in nondiabetic first-degree 

relatives of individuals with type 2 diabetes. Diabetes 1998 

May;47(5):788-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Islam-Zwart K, Cawston A. Investigation of factors 

contributing to diabetes risk in american indian/alaska 

native youth. Am Indian Alsk Native Ment Health Res 

2008;14(3):49-58. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ivanovich J, Babb S, Goodfellow P, et al. Evaluation of the 

family history collection process and the accuracy of cancer 

reporting among a series of women with endometrial 

cancer. Clin Cancer Res 2002 Jun;8(6):1849-56. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Iwata F, Okada T, Harada K, et al. Coronary risk factors in 

school children in relation to their family history of 

coronary heart disease and hyperlipidemia. Acta Paediatr 

Jpn 1998 Feb;40(1):30-4. 

Excluded because no eligible outcomes presented 

Jacobs LA. Health beliefs of first-degree relatives of 

individuals with colorectal cancer and participation in 

health maintenance visits: a population-based survey. 

Cancer Nurs 2002 Aug;25(4):251-65. 

Excluded because no eligible outcomes presented 

D-31
Jacobsen PB, Lamonde LA, Honour M, et al. Relation of 

family history of prostate cancer to perceived vulnerability 

and screening behavior. Psychooncology 2004 

Feb;13(2):80-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jaddou HY, Batiehah AM, Ajlouni KM. Prevalence and 

associated factors of hypertension: Results from a three 

community-based survey, Jordan. J Hum Hypertens 

1996;10(12):815-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jakubowska A, Cybulski C, Szymanska A, et al. BARD1 

and breast cancer in Poland. Breast Cancer Res Treat 2008 

Jan;107(1):119-22. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Janda M, Obermair A, Haidinger G, et al. Austrian 

women's attitudes toward and knowledge of breast selfexamination. J Cancer Educ 2000;15(2):91-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jansson PA, Eliasson B, Lindmark S, et al. Endocrine 

abnormalities in healthy first-degree relatives of type 2 

diabetes patients--potential role of steroid hormones and 

leptin in the development of insulin resistance. Eur J Clin 

Invest 2002 Mar;32(3):172-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jarvinen HJ, Mecklin JP, Sistonen P. Screening reduces 

colorectal cancer rate in families with hereditary 

nonpolyposis colorectal cancer. Gastroenterology 1995 

May;108(5):1405-11. 

Excluded because no eligible outcomes presented 

Jaworowska E, Serrano-Fernandez P, Tarnowska C, et al. 

Familial association of laryngeal, lung, stomach and earlyonset breast cancer. Breast Cancer Res Treat 2008 

Nov;112(2):359-61. 

Excluded because no eligible outcomes presented 

Jenei Z, Pall D, Katona E, et al. The epidemiology of 

hypertension and its associated risk factors in the city of 

Debrecen, Hungary. Public Health 2002;116(3):138-44. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jerrard-Dunne P, Markus HS, Steckel DA, et al. Early 

carotid atherosclerosis and family history of vascular 

disease: specific effects on arterial sites have implications 

for genetic studies. Arterioscler Thromb Vasc Biol 2003 

Feb 1;23(2):302-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jerrard-Dunne P, Cloud G, Hassan A, et al. Evaluating the 

genetic component of ischemic stroke subtypes: a family 

history study. Stroke 2003 Jun;34(6):1364-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ji J, Hemminki K. Risk for contralateral breast cancers in a 

population covered by mammography: effects of family 

history, age at diagnosis and histology. Breast Cancer Res 

Treat 2007 Oct;105(2):229-36. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ji J, Forsti A, Sundquist J, et al. Survival in ovarian cancer 

patients by histology and family history. Acta Oncol 

2008;47(6):1133-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jimenez-Moleon JJ, Bueno-Cavanillas A, Luna-del-Castillo 

JD, et al. Predictive value of a screen for gestational 

diabetes mellitus: Influence of associated risk factors. Acta 

Obstet Gynecol Scand 2000;79(11):991-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jimenez-Moleon JJ, Bueno-Cavanillas A, Luna-del-Castillo 

JD, et al. Prevalence of gestational diabetes mellitus: 

Variations related to screening strategy used. EUR 

2002;146(6):831-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jin Y, Xu Y, Xu M, et al. Increased risk of cancer among 

relatives of patients with lung cancer in China. BMC 

Cancer 2005;5:146 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-32
and outcome criteria were met for the review questions in 

aggregate 

Jin YT, Xu YC, Yang RD, et al. Familial aggregation of 

lung cancer in a high incidence area in China. Br J Cancer 

2005 Apr 11;92(7):1321-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Johns LE, Kee F, Collins BJ, et al. Colorectal cancer 

mortality in first-degree relatives of early-onset colorectal 

cancer cases. Dis Colon Rectum 2002 May;45(5):681-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Johnson CC, Ownby DR, Peterson EL. Parental history of 

atopic disease and concentration of cord blood IgE. Clin 

Exp Allergy 1996 Jun;26(6):624-9. 

Excluded because no eligible outcomes presented 

Johnson J, Giles RT, Larsen L, et al. Utah's Family High 

Risk Program: bridging the gap between genomics and 

public health. Prev Chronic Dis 2005 Apr;2(2):A24 

Excluded because not an eligible study design 

Johnson KC, Pan S, Mao Y. Risk factors for male breast 

cancer in Canada, 1994-1998. Eur J Cancer Prev 

2002;11(3):253-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jones AP, Eyles E. Early life exposures and the prevalence 

of atopic disoders in a sample of school-age infants. 

Monaldi Arch Chest Dis 2003;59(1):38-43. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jones JL, Hughes KS, Kopans DB, et al. Evaluation of 

hereditary risk in a mammography population. Clin Breast 

Cancer 2005 Apr;6(1):38-44. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jonsson S, Thorsteinsdottir U, Gudbjartsson DF, et al. 

Familial risk of lung carcinoma in the Icelandic population. 

[erratum appears in JAMA. 2005 Jan 12;293(2):163]. 

JAMA 2004 Dec 22;292(24):2977-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jood K, Ladenvall C, Rosengren A, et al. Family history in 

ischemic stroke before 70 years of age: the Sahlgrenska 

Academy Study on Ischemic Stroke. Stroke 2005 

Jul;36(7):1383-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Jousilahti P, Rastenyte D, Tuomilehto J, et al. Parental 

history of cardiovascular disease and risk of stroke. A 

prospective follow-up of 14371 middle-aged men and 

women in Finland. Stroke 1997 Jul;28(7):1361-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Joyce DP, Chapman KR, Balter M, et al. Asthma and 

allergy avoidance knowledge and behavior in postpartum 

women. Ann Allergy Asthma Immunol 1997 Jul;79(1):35-

42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Juonala M, Viikari JS, Rasanen L, et al. Young adults with 

family history of coronary heart disease have increased 

arterial vulnerability to metabolic risk factors: the 

Cardiovascular Risk in Young Finns Study. Arterioscler 

Thromb Vasc Biol 2006 Jun;26(6):1376-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kadiki OA, Roaeid RB. Prevalence of diabetes mellitus and 

impaired glucose tolerance in Benghazi Libya. Diabetes 

Metab 2001;27(6):647-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kaerlev L, Lynge E, Sabroe S, et al. Reliability of data 

from next-of-kin: results from a case-control study of 

occupational and lifestyle risk factors for cancer. Am J Ind 

Med 2003 Sep;44(3):298-303. 

Excluded because family history not collected 

Kahn JS, Weseley AJ. When the third degree is necessary: 

Do pediatricians obtain enough information to detect 

patients at risk for HCM? Pediatr Cardiol 2008;29(3):589-

96. 

Excluded because family history not collected 

Kaikkonen KS, Kortelainen ML, Linna E, et al. Family 

history and the risk of sudden cardiac death as a 

manifestation of an acute coronary event. Circulation 2006 

Oct 3;114(14):1462-7. 

D-33
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kalyoncu AF, Selcuk ZT, Enunlu T, et al. Prevalence of 

asthma and allergic diseases in primary school children in 

Ankara, Turkey: Two cross-sectional studies, five years 

apart. Pediatr Allergy Immunol 1999;10(4):261-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kanitz MG, Giovannucci SJ, Jones JS, et al. Myocardial 

infarction in young adults: Risk factors and clinical 

features. J Emerg Med 1996;14(2):139-45. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Karadzinska-Bislimovska J, Minov J, Risteska-Kuc S, et al. 

Bronchial hyperresponsiveness in women cooks and 

cleaners. Arh Hig Rada Toksikol 2007;58(2):223-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kardia SL, Haviland MB, Sing CF. Correlates of family 

history of coronary artery disease in children. J Clin 

Epidemiol 1998 Jun;51(6):473-86. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Karlsson CT, Malmer B, Wiklund F, et al. Breast cancer as 

a second primary in patients with prostate cancer--estrogen 

treatment or association with family history of cancer? J 

Urol 2006 Aug;176(2):538-43. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Karner-Hanusch J, Mittlbock M, Fillipitsch T, et al. Family 

history as a marker of risk for colorectal cancer: Austrian 

experience. World J Surg 1997 Feb;21(2):205-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Karunasekera KAW, Jayasinghe JACT, Alwis LWGR. 

Risk factors of childhood asthma: A Sri Lankan study. J 

Trop Pediatr 2001;47(3):142-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Katballe N, Juul S, Christensen M, et al. Patient accuracy 

of reporting on hereditary non-polyposis colorectal cancerrelated malignancy in family members. Br J Surg 2001 

Sep;88(9):1228-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Katelaris CH, Carrozzi FM, Burke TV, et al. Patterns of 

allergic reactivity and disease in Olympic athletes. Clin J 

Sport Med 2006;16(5):401-5. 

Excluded because no eligible outcomes presented 

Katsouyanni K, Signorello LB, Lagiou P, et al. Evidence 

that adult life risk factors influence the expression of 

familial propensity to breast cancer. Epidemiology 1997 

Sep;8(5):592-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kavanagh T, Shephard RJ, Hamm LF, et al. Risk profile 

and health awareness in male offspring of parents with 

premature coronary heart disease. J Cardpulm Rehabil 2000 

May;20(3):172-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kawano H, Soejima H, Kojima S, et al. Sex differences of 

risk factors for acute myocardial infarction in Japanese 

patients. Circ J 2006 May;70(5):513-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kawasaki K, Kanemitsu K, Yasuda T, et al. Family history 

of cancer in Japanese gastric cancer patients. Gastric 

Cancer 2007;10(3):173-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kazerouni N, Greene MH, Lacey JV, Jr., et al. Family 

history of breast cancer as a risk factor for ovarian cancer 

in a prospective study. Cancer 2006 Sep 1;107(5):1075-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Keetch DW, Rice JP, Suarez BK, et al. Familial aspects of 

prostate cancer: A case control study. J Urol 

1995;154(6):2100-2. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-34
and outcome criteria were met for the review questions in 

aggregate 

Kekalainen P, Sarlund H, Pyorala K, et al. Family history 

of coronary heart disease is a stronger predictor of coronary 

heart disease morbidity and mortality than family history of 

non-insulin dependent diabetes mellitus. Atherosclerosis 

1996 Jun;123(1-2):203-13. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kelishadi R, Ardalan G, Gheiratmand R, et al. Is family 

history of premature cardiovascular diseases appropriate for 

detection of dyslipidemic children in population-based 

preventive medicine programs? CASPIAN study. Pediatr 

Cardiol 2006 Nov;27(6):729-36. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kelleher CC, Fallon UB, Fitzsimon N, et al. The risk factor 

profile of grandparents. Ir Med J 2007 Sep;100(8):15-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Keller M, Jost R, Haunstetter CM, et al. Psychosocial 

outcome following genetic risk counselling for familial 

colorectal cancer. A comparison of affected patients and 

family members. Clin Genet 2008 Nov;74(5):414-24. 

Excluded because no eligible outcomes presented 

Kelly LA, Lane CJ, Weigensberg MJ, et al. Parental history 

and risk of type 2 diabetes in overweight Latino 

adolescents: a longitudinal analysis. Diabetes Care 2007 

Oct;30(10):2700-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kendler KS, Roy MA. Validity of a diagnosis of lifetime 

major depression obtained by personal interview versus 

family history. Am J Psychiatry 1995 Nov;152(11):1608-

14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kerber RA, Slattery ML. The impact of family history on 

ovarian cancer risk. The Utah Population Database. Arch 

Intern Med 1995 May 8;155(9):905-12. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kerber RA, Slattery ML, Potter JD, et al. Risk of colon 

cancer associated with a family history of cancer or 

colorectal polyps: the diet, activity, and reproduction in 

colon cancer study. Int J Cancer 1998 Oct 5;78(2):157-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kerber RA, O'Brien E. A cohort study of cancer risk in 

relation to family histories of cancer in the Utah population 

database. Cancer 2005;103(9):1906-15. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kerr B, Foulkes WD, Cade D, et al. False family history of 

breast cancer in the family cancer clinic. Eur J Surg Oncol 

1998 Aug;24(4):275-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Khuwaja AK, Fatmi Z, Soomro WB, et al. Risk Factors for 

Cardiovascular Disease in School Children - A Pilot Study. 

J Pak Med Assoc 2003;53(9):396-400. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kilfoy BA, Zhang Y, Shu XO, et al. Family history of 

malignancies and risk of breast cancer: prospective data 

from the Shanghai women's health study. Cancer Causes 

Control 2008 Dec;19(10):1139-45. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kim CW, Park CJ, Kim JW, et al. Prevalence of atopic 

dermatitis in Korea. Acta Derm Venereol 2000;80(5):353-

6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kim H, Friedlander Y, Longstreth WT, Jr., et al. Family 

history as a risk factor for stroke in young women. Am J 

Prev Med 2004 Dec;27(5):391-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kim SM, Lee JS, Lee J, et al. Prevalence of diabetes and 

impaired fasting glucose in Korea: Korean National Health 

and Nutrition Survey 2001. Diabetes Care 2006;29(2):226-

31. 

D-35
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

King CA, Knox MS, Henninger N, et al. Major depressive 

disorder in adolescents: family psychiatric history predicts 

severe behavioral disinhibition. J Affect Disord 2006 

Feb;90(2-3):111-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

King M, Walker C, Levy G, et al. Development and 

validation of an international risk prediction algorithm for 

episodes of major depression in general practice attendees: 

The predictD study. Arch Gen Psychiatry 

2008;65(12):1368-76. 

Excluded because no eligible outcomes presented 

Kinmonth AL, Wareham NJ, Hardeman W, et al. Efficacy 

of a theory-based behavioural intervention to increase 

physical activity in an at-risk group in primary care 

(ProActive UK): A randomised trial. Lancet 2008 

Jan;371(9606):41-8. 

Excluded because no eligible outcomes presented 

Kinney AY, Hicken B, Simonsen SE, et al. Colorectal 

cancer surveillance behaviors among members of typical 

and attenuated FAP families. Am J Gastroenterol 2007 

Jan;102(1):153-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Klein Woolthuis EP, de Grauw WJC, van Gerwen WHEM, 

et al. Identifying people at risk for undiagnosed type 2 

diabetes using the GP's electronic medical record. Fam 

Pract 2007;24(3):230-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Klein BE, Klein R, Moss SE, et al. Parental history of 

diabetes in a population-based study. Diabetes Care 1996 

Aug;19(8):827-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Klein DN, Lewinsohn PM, Seeley JR, et al. A family study 

of major depressive disorder in a community sample of 

adolescents. Arch Gen Psychiatry 2001 Jan;58(1):13-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Klein DN, Shankman SA, Lewinsohn PM, et al. Family 

study of chronic depression in a community sample of 

young adults. Am J Psychiatry 2004 Apr;161(4):646-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Knuiman MW, Divitini ML, Welborn TA, et al. Familial 

correlations, cohabitation effects, and heritability for 

cardiovascular risk factors. Ann Epidemiol 1996 

May;6(3):188-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ko GTC, Chan JCN, Tsang LWW, et al. Outcomes of 

screening for diabetes in high-risk Hong Kong Chinese 

subjects. Diabetes Care 2000;23(9):1290-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ko GTC, Chan JCN, Tsang LWW, et al. Smoking and 

diabetes in Chinese men. Postgrad Med J 

2001;77(906):240-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kocic B, Petrovic B, Filipovic S. Risk factors for breast 

cancer: A hospital-based case-control study. J BUON 

2008;13(2):231-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kodali VR, Seshaiah V, Moses SG. Body mass index and 

family histories in type II diabetic propositi and preliminary 

observations on the transmission of diabetes in polygamous 

families. Hum Biol 1997 Jun;69(3):393-402. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Koehly LM, Peters JA, Kuhn N, et al. Sisters in hereditary 

breast and ovarian cancer families: Communal coping, 

social integration, and psychological well-being. 

Psychooncology 2008;17(8):812-21. 

Excluded because not an eligible population 

Koh YY, Lee MH, Sun YH, et al. Improvement in 

bronchial hyperresponsiveness with inhaled corticosteroids 

in children with asthma: importance of family history of 

bronchial hyperresponsiveness. Am J Respir Crit Care Med 

2002 Aug 1;166(3):340-5. 

D-36
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kojo K, Pukkala E, Auvinen A. Breast cancer risk among 

Finnish cabin attendants: A nested case-control study. 

Occup Environ Med 2005;62(7):488-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kok ET, Schouten BW, Bohnen AM, et al. Risk factors for 

lower urinary tract symptoms suggestive of benign 

prostatic hyperplasia in a community based population of 

healthy aging men: the Krimpen Study. J Urol 2009 

Feb;181(2):710-6. 

Excluded because no eligible outcomes presented 

Koopman RJ, Mainous III AG, Everett CJ, et al. Tool to 

assess likelihood of fasting glucose impairment (TAG-IT). 

Ann Fam Med 2008;6(6):555-61. 

Excluded because no eligible outcomes presented 

Kotake K, Koyama Y, Nasu J, et al. Relation of family 

history of cancer and environmental factors to the risk of 

colorectal cancer: a case-control study. Jpn J Clin Oncol 

1995 Oct;25(5):195-202. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kovacs M, Devlin B, Pollock M, et al. A controlled family 

history study of childhood-onset depressive disorder. Arch 

Gen Psychiatry 1997 Jul;54(7):613-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kreuzer M, Kreienbrock L, Gerken M, et al. Risk factors 

for lung cancer in young adults. Am J Epidemiol 1998 Jun 

1;147(11):1028-37. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kronmal RA, McClelland RL, Detrano R, et al. Risk 

factors for the progression of coronary artery calcification 

in asymptomatic subjects: Results from the Multi-Ethnic 

Study of Atherosclerosis (MESA). Circulation 

2007;115(21):2722-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kubota M, Yamaura A, Ono J, et al. Is family history an 

independent risk factor for stroke? J Neurol Neurosurg 

Psychiatry 1997 Jan;62(1):66-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kumar R, Wang B, Wang X, et al. Bronchodilator 

responses in Chinese children from asthma index families 

and the general population. J Allergy Clin Immunol 

2006;117(6):1257-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kummeling I, Thijs C, Penders J, et al. Etiology of atopy in 

infancy: the KOALA Birth Cohort Study. Pediatr Allergy 

Immunol 2005 Dec;16(8):679-84. 

Excluded because no eligible outcomes presented 

Kupfer SS, McCaffrey S, Kim KE. Racial and gender 

disparities in hereditary colorectal cancer risk assessment: 

the role of family history. J Cancer Educ 2006;21(Suppl 

1):S31-S36 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kuriki K, Hirose K, Tajima K. Diabetes and cancer risk for 

all and specific sites among Japanese men and women. Eur 

J Cancer Prev 2007 Feb;16(1):83-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kuru B, Ozaslan C, Ozdemir P, et al. Risk factors for breast 

cancer in Turkish women with early pregnancies and longlasting lactation - A case-control study. Acta Oncol 

2002;41(6):556-61. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kurukulaaratchy RJ, Matthews S, Arshad SH. Relationship 

between childhood atopy and wheeze: what mediates 

wheezing in atopic phenotypes? Ann Allergy Asthma 

Innunol 2006 Jul;97(1):84-91. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Kushner JD, Nauman D, Burgess D, et al. Clinical 

characteristics of 304 kindreds evaluated for familial 

dilated cardiomyopathy. J Card Fail 2006 Aug;12(6):422-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-37
and outcome criteria were met for the review questions in 

aggregate 

Lagos VI, Perez MA, Ricker CN, et al. Social-cognitive 

aspects of underserved Latinas preparing to undergo 

genetic cancer risk assessment for hereditary breast and 

ovarian cancer. Psychooncology 2008;17(8):774-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Laing SS, Makambi K. Predicting regular breast cancer 

screening in African-American women with a family 

history of breast cancer. J Natl Med Assoc 2008 

Nov;100(11):1309-17. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lam DSY, Leung SP, So KT. Age of onset of asthma 

symptoms. HK J Paediatr 2007;12(1):11-4+61. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lancaster DR. Coping with appraised breast cancer risk 

among women with family histories of breast cancer. Res 

Nurs Health 2005 Apr;28(2):144-58. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Langdeau J-B, Turcotte H, Thibault G, et al. Comparative 

prevalence of asthma in different groups of athletes: A 

survey. Can Respir J 2004;11(6):402-6. 

Excluded because no eligible outcomes presented 

Larsen FS, Diepgen T, Svensson A. The occurrence of 

atopic dermatitis in North Europe: An international 

questionnaire study. J Am Acad Dermatol 1996;34(5 

I):760-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lascaux-Lefebvre V, Ruidavets JB, Arveiler D, et al. 

Influence of parental histories of cardiovascular risk factors 

on risk factor clusters in the offspring. Diabetes Metab 

2001;27(4 I):503-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Latzin P, Beck J, Griese M. Exhaled nitric oxide in healthy 

children: variability and a lack of correlation with atopy. 

Pediatr Allergy Immunol 2002 Feb;13(1):37-46. 

Excluded because no eligible outcomes presented 

Laubereau B, Brockow I, Zirngibl A, et al. Effect of breastfeeding on the development of atopic dermatitis during the 

first 3 years of life - Results from the gini-birth cohort 

study. J Pediatr 2004;144(5):602-7. 

Excluded because no eligible outcomes presented 

Laukkanen JA, Rauramaa R, Salonen JT, et al. The 

predictive value of cardiorespiratory fitness combined with 

coronary risk evaluation and the risk of cardiovascular and 

all-cause death. J Intern Med 2007;262(2):263-72. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lawrence JM, Bennett P, Young A, et al. Screening for 

diabetes in general practice: Cross sectional population 

study. Br Med J 2001;323(7312):548-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Le Marchand L, Zhao LP, Quiaoit F, et al. Family history 

and risk of colorectal cancer in the multiethnic population 

of Hawaii. Am J Epidemiol 1996 Dec 15;144(12):1122-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Le Marchand L, Wilkens LR, Hankin JH, et al. 

Independent and joint effects of family history and lifestyle 

on colorectal cancer risk: Implications for prevention. 

Cancer Epidemiol Biomarkers Prev 1999;8(1):45-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Leander K, Hallqvist J, Reuterwall C, et al. Family history 

of coronary heart disease, a strong risk factor for 

myocardial infarction interacting with other cardiovascular 

risk factors: results from the Stockholm Heart 

Epidemiology Program (SHEEP). Epidemiology 2001 

Mar;12(2):215-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lecomte P, Vol S, Caces E, et al. Five-year predictive 

factors of type 2 diabetes in men with impaired fasting 

glucose. Diabetes Metab 2007;33(2):140-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-38
Lee EO, Ahn SH, You C, et al. Determining the main risk 

factors and high-risk groups of breast cancer using a 

predictive model for breast cancer risk assessment in South 

Korea. Cancer Nurs 2004 Sep;27(5):400-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lee ET, Howard BV, Savage PJ, et al. Diabetes and 

impaired glucose tolerance in three American Indian 

populations aged 45-74 years: The strong heart study. 

Diabetes Care 1995;18(5):599-610. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lee JT, Lam ZC, Lee WT, et al. Familial risk of allergic 

rhinitis and atopic dermatitis among Chinese families in 

Singapore. Ann Acad Med Singapore 2004 Jan;33(1):71-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lee W-Y, Jung C-H, Park J-S, et al. Effects of smoking, 

alcohol, exercise, education, and family history on the 

metabolic syndrome as defined by the ATP III. Diabetes 

Res Clin Pract 2005;67(1):70-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Leggatt V, Mackay J, Yates JR. Evaluation of 

questionnaire on cancer family history in identifying 

patients at increased genetic risk in general practice. BMJ 

1999 Sep 18;319(7212):757-8. 

Excluded because no eligible outcomes presented 

Lehmann I, Thoelke A, Weiss M, et al. T cell reactivity in 

neonates from an East and a West German city - Results of 

the LISA study. Allergy 2002;57(2):129-36. 

Excluded because no eligible outcomes presented 

Lerbaek A, Kyvik KO, Mortensen J, et al. Heritability of 

hand eczema is not explained by comorbidity with atopic 

dermatitis. J Invest Dermatol 2007 Jul;127(7):1632-40. 

Excluded because family history not collected 

Lesko SM, Rosenberg L, Shapiro S. Family history and 

prostate cancer risk. Am J Epidemiol 1996 Dec 

1;144(11):1041-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Leu M, Reilly M, Czene K. Evaluation of bias in familial 

risk estimates: A study of common cancers using Swedish 

population-based registers. J Natl Cancer Inst 

2008;100(18):1318-25. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Leung R, Ho P, Lam CW, et al. Sensitization to inhaled 

allergens as a risk factor for asthma and allergic diseases in 

Chinese population. J Allergy Clin Immunol 1997 

May;99(5):594-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Leung TF, Tam WH, Hung ECW, et al. Sociodemographic 

and atopic factors affecting breastfeeding intention in 

Chinese mothers. J Paediatr Child Health 2003;39(6):460-

4. 

Excluded because no eligible outcomes presented 

Levesque B, Rhainds M, Ernst P, et al. Asthma and allergic 

rhinitis in Quebec children. Can Respir J 2004;11(5):343-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Levesque B, Duchesne J-F, Gingras S, et al. Total and 

specific immunoglobulin E and their relationship to 

respiratory symptoms in Quebec children and adolescents. 

Can Respir J 2005;12(8):426-32. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Levy AG, Shea J, Williams SV, et al. Measuring 

perceptions of breast cancer risk. Cancer Epidemiol 

Biomarkers Prev 2006;15(10):1893-8. 

Excluded because no eligible outcomes presented 

Lewinsohn PM, Rohde P, Seeley JR, et al. Natural course 

of adolescent major depressive disorder in a community 

sample: predictors of recurrence in young adults. Am J 

Psychiatry 2000 Oct;157(10):1584-91. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Li G, Aryan M, Silverman JM, et al. The validity of the 

family history method for identifying Alzheimer disease. 

Arch Neurol 1997 May;54(5):634-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Li H, Xu T, Tong W, et al. Comparison of cardiovascular 

risk factors between prehypertension and hypertension in a 

D-39
Mongolian population, Inner Mongolia, China. Circ J 2008 

Oct;72(10):1666-73. 

Excluded because no eligible outcomes presented 

Li R, Bensen JT, Hutchinson RG, et al. Family risk score of 

coronary heart disease (CHD) as a predictor of CHD: the 

Atherosclerosis Risk in Communities (ARIC) study and the 

NHLBI family heart study. Genet Epidemiol 2000 

Mar;18(3):236-50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Li R, Gilliland FD, Baumgartner KB, et al. Family history 

and risk of breast cancer in hispanic and non-hispanic 

women: the New Mexico Women's Health Study. Cancer 

Causes Control 2001 Oct;12(8):747-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Li X, Hemminki K. Inherited predisposition to early onset 

lung cancer according to histological type. Int J Cancer 

2004 Nov 10;112(3):451-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Li X, Hemminki K. Familial multiple primary lung cancers: 

a population-based analysis from Sweden. Lung Cancer 

2005 Mar;47(3):301-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Li X, Sundquist J, Sundquist K. Age-specific familial risks 

of depression: A nation-wide epidemiological study from 

Sweden. J Psychiatr Res 2008 Aug;42(10):808-14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Liang PH, Shyur SD, Huang LH, et al. Risk factors and 

characteristics of early-onset asthma in Taiwanese children. 

J Microbiol Immunol Infect 2006 Oct;39(5):414-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Liao D, Myers R, Hunt S, et al. Familial history of stroke 

and stroke risk. The Family Heart Study. Stroke 1997 

Oct;28(10):1908-12. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lidfeldt J, Nyberg P, Nerbrand C, et al. Biological factors 

are more important than socio-demographic and 

psychosocial conditions in relation to hypertension in 

middle-aged women. The Women's Health in the Lund 

Area (WHILA) Study. Blood Press 2002;11(5):270-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lieb R, Isensee B, Hofler M, et al. Parental major 

depression and the risk of depression and other mental 

disorders in offspring: a prospective-longitudinal 

community study. Arch Gen Psychiatry 2002 

Apr;59(4):365-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lieberman DA, Prindiville S, Weiss DG, et al. Risk factors 

for advanced colonic neoplasia and hyperplastic polyps in 

asymptomatic individuals. JAMA 2003 Dec 

10;290(22):2959-67. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lightfoot N, Conlon M, Kreiger N, et al. Medical history, 

sexual, and maturational factors and prostate cancer risk. 

Ann Epidemiol 2004 Oct;14(9):655-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lindahl MG, Barrett R, Peterson D, et al. Development of 

an integrative patient history intake tool: a Delphi study. 

Altern Ther Health Med 2005 Jan;11(1):52-6. 

Excluded because family history not collected 

Lindgren A, Lovkvist H, Hallstrom B, et al. Prevalence of 

stroke and vascular risk factors among first-degree relatives 

of stroke patients and control subjects. A prospective 

consecutive study. Cerebrovasc Dis 2005;20(5):381-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lindstrom M, Kotaniemi J, Jonsson E, et al. Smoking, 

respiratory symptoms, and diseases: A comparative study 

between northern Sweden and northern Finland: Report 

from the FinEsS study. Chest 2001;119(3):852-61. 

Excluded because no eligible outcomes presented 

Lippert MT, Eaker ED, Vierkant RA, et al. Breast cancer 

screening and family history among rural women in 

Wisconsin. Cancer Detect Prev 1999;23(3):265-72. 

D-40
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lisabeth LD, Kardia SL, Smith MA, et al. Family history 

of stroke among Mexican-American and non-Hispanic 

white patients with stroke and TIA: implications for the 

feasibility and design of stroke genetics research. 

Neuroepidemiology 2005;24(1-2):96-102. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lisabeth LD, Smith MA, Brown DL, et al. Family history 

and stroke outcome in a bi-ethnic, population-based stroke 

surveillance study. BMC Neurol 2005;5:20 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Liu X, Sennett C, Legorreta AP. Mammography utilization 

among California women age 40-49 in a managed care 

environment. Breast Cancer Res Treat 2001 

May;67(2):181-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lizardi H, Klein DN. Parental psychopathology and reports 

of the childhood home environment in adults with earlyonset dysthymic disorder. J Nerv Ment Dis 2000 

Feb;188(2):63-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Loader S, Shields C, Levenkron JC, et al. Patient vs. 

physician as the target of educational outreach about 

screening for an inherited susceptibility to colorectal 

cancer. Genet Test 2002;6(4):281-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lodrup Carlsen KC, Pettersen M, Carlsen K-H. Is 

bronchodilator response in 2-yr-old children associated 

with asthma risk factors? Pediatr Allergy Immunol 

2004;15(4):323-30. 

Excluded because no eligible outcomes presented 

Longacre AV, Cramer LD, Gross CP. Screening 

colonoscopy use among individuals at higher colorectal 

cancer risk. J Clin Gastroenterol 2006 Jul;40(6):490-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Loock M, Steyn K, Becker P, et al. Coronary heart disease 

and risk factors in Black South Africans: a case-control 

study. Ethn Dis 2006;16(4):872-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lopez-Perez G, Morfin-Maciel B, Hernandez T, et al. 

Prevalence of atopic dermatitis in a group of children in 

Mexico City. Allergy Clin Immunol Int 2001;13(6):236-41. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lorenzo BJ, Hemminki K. Risk of cancer at sites other than 

the breast in Swedish families eligible for BRCA1 or 

BRCA2 mutation testing. Ann Oncol 2004 

Dec;15(12):1834-41. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Loscalzo ML, Goh DL, Loeys B, et al. Familial thoracic 

aortic dilation and bicommissural aortic valve: a 

prospective analysis of natural history and inheritance. Am 

J Med Genet 2007 Sep 1;Part(17):1960-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lotfi MH, Charkhatti S, Shobairi S. Breast cancer risk 

factors in an urban area of Yazd city- Iran, 2006. Acta Med 

Iran 2008;46(3):258-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Low NC, Cui L, Merikangas KR. Specificity of familial 

transmission of anxiety and comorbid disorders. J Psychiatr 

Res 2008 Jun;42(7):596-604. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lowery JT, Byers T, Axell L, et al. The impact of direct-toconsumer marketing of cancer genetic testing on women 

according to their genetic risk. Genet Med 2008 

Dec;10(12):888-94. 

Excluded because family history not collected 

Lubin F, Chetrit A, Freedman LS, et al. Body mass index at 

age 18 years and during adult life and ovarian cancer risk. 

Am J Epidemiol 2003;157(2):113-20. 

D-41
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Luby JL, Belden AC, Spitznagel E. Risk factors for 

preschool depression: The mediating role of early stressful 

life events. J Child Psychol Psychiatry 2006;47(12):1292-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ludvigsson JF, Mostrom M, Ludvigsson J, et al. Exclusive 

breastfeeding and risk of atopic dermatitis in some 8300 

infants. Pediatr Allergy Immunol 2005;16(3):201-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lundback B, Ronmark E, Jonsson E, et al. Incidence of 

physician-diagnosed asthma in adults - A real incidence or 

a result of increased awareness? Report from the 

obstructive lung disease in Northern Sweden studies. 

Respir Med 2001;95(8):685-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lyketsos CG, Tune LE, Pearlson G, et al. Major depression 

in Alzheimer's disease. An interaction between gender and 

family history. Psychosomatics 1996 Jul;37(4):380-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lynch KL, Ahnen DJ, Byers T, et al. First-degree relatives 

of patients with advanced colorectal adenomas have an 

increased prevalence of colorectal cancer. Clin 

Gastroenterol Hepatol 2003 Mar;1(2):96-102. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Lyssenko V, Almgren P, Anevski D, et al. Predictors of and 

longitudinal changes in insulin sensitivity and secretion 

preceding onset of type 2 diabetes. Diabetes 2005 

Jan;54(1):166-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

MacClellan LR, Mitchell BD, Cole JW, et al. Familial 

aggregation of ischemic stroke in young women: the Stroke 

Prevention in Young Women Study. Genet Epidemiol 2006 

Nov;30(7):602-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

MacDonald DJ, Sarna L, Uman GC, et al. Health beliefs of 

women with and without breast cancer seeking genetic 

cancer risk assessment. Cancer Nurs 380 Jan;28(5):372-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

MacDonald DJ, Sarna L, Giger JN, et al. Comparison of 

Latina and non-Latina white women's beliefs about 

communicating genetic cancer risk to relatives. J Health 

Commun 2008;13(5):465-79. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mack LA, Stuart H, Temple WJ. Survey of colorectal 

cancer screening practices in a large Canadian urban centre. 

Can J Surg 2004 Jun;47(3):189-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mackay J, Rogers C, Fielder H, et al. Development of a 

protocol for evaluation of mammographic surveillance 

services in women under 50 with a family history of breast 

cancer. J Epidemiol Biostat 371 May;6(5):365-9. 

Excluded because not an eligible study design 

MacLeod HM, McNally EM. A pilot study of a family 

history risk assessment tool for cardiovascular disease. J 

Genet Couns 2008 Oct;17(5):499-507. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Macmillan RD. Screening women with a family history of 

breast cancer--results from the British Familial Breast 

Cancer Group. Eur J Surg Oncol 2000 Mar;26(2):149-52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Madlensky L, Esplen MJ, Gallinger S, et al. Relatives of 

colorectal cancer patients: factors associated with screening 

behavior. Am J Prev Med 2003 Oct;25(3):187-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-42
Madlensky L, Vierkant RA, Vachon CM, et al. Preventive 

health behaviors and familial breast cancer. Cancer 

Epidemiol Biomarkers Prev 2005;14(10):2340-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Madlensky L, Flatt SW, Bardwell WA, et al. Is family 

history related to preventive health behaviors and medical 

management in breast cancer patients? Breast Cancer Res 

Treat 2005 Mar;90(1):47-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Magnusson C, Colditz G, Rosner B, et al. Association of 

family history and other risk factors with breast cancer risk 

(Sweden). Cancer Causes Control 1998 May;9(3):259-67. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Magura L, Blanchard R, Hope B, et al. 

Hypercholesterolemia and prostate cancer: a hospital-based 

case-control study. Cancer Causes Control 2008 

Dec;19(10):1259-66. 

Excluded because no eligible outcomes presented 

Mahdavinia M, Bishehsari F, Ansari R, et al. Family 

history of colorectal cancer in Iran. BMC Cancer 

2005;5:112 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mahouri K, Dehghani ZM, Zare S. Breast cancer risk 

factors in south of Islamic Republic of Iran: a case-control 

study. East Mediterr Health J 2007 Nov;13(6):1265-73. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mainous III AG, Koopman RJ, Diaz VA, et al. A Coronary 

Heart Disease Risk Score Based on Patient-Reported 

Information. Am J Cardiol 2007;99(9):1236-41. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Majeed R, Rajar UDM, Shaikh N, et al. Risk factors 

associated with childhood asthma. J Coll Physicians Surg 

Pak 2008;18(5):299-302. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mancuso C, Glendon G, Anson-Cartwright L, et al. 

Ethnicity, but not cancer family history, is related to 

response to a population-based mailed questionnaire. Ann 

Epidemiol 2004 Jan;14(1):36-43. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mansur ADP, Gomes EPSG, Avakian SD, et al. Clustering 

of traditional risk factors and precocity of coronary disease 

in women. Int J Cardiol 2001;81(2-3):205-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Manuel DG, Wilson S, Maaten S. The 2006 Canadian 

dyslipidemia guidelines will prevent more deaths while 

treating fewer people - But should they be further 

modified? Can J Cardiol 2008;24(8):617-20. 

Excluded because family history not collected 

Marcus GM, Smith LM, Vittinghoff E, et al. A first-degree 

family history in lone atrial fibrillation patients. Heart 

Rhythm 2008;5(6):826-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Margolin S, Johansson H, Rutqvist LE, et al. Family 

history, and impact on clinical presentation and prognosis, 

in a population-based breast cancer cohort from the 

Stockholm County. Fam Cancer 2006;5(4):309-21. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Marotte JB, Ferrari MK, McNeal JE, et al. Time trends in 

pathologic features of radical prostatectomy--impact of 

family history. Urol Oncol 2004 May;22(3):169-73. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Martin W, Degner L. Perception of risk and surveillance 

practices of women with a family history of breast cancer. 

Cancer Nurs 2006 May;29(3):227-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Martin WL. Perception of risk and surveillance practices 

for women with a family history of breast cancer. Can 

Oncol Nurs J 2003;13(2):131 

Excluded because not an eligible study design 

D-43
Marusic A. Factor analysis of risk for coronary heart 

disease: An independent replication. Int J Cardiol 

2000;75(2-3):233-8. 

Excluded because no eligible outcomes presented 

Mastalski K, Coups EJ, Ruth K, et al. Substantial family 

history of prostate cancer in black men recruited for 

prostate cancer screening: results from the Prostate Cancer 

Risk Assessment Program. Cancer 2008 Nov 

1;113(9):2559-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Masuo K, Mikami H, Ogihara T, et al. Familial 

hypertension, insulin, sympathetic activity, and blood 

pressure elevation. Hypertension 1998 Jul;32(1):96-100. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Matakidou A, Eisen T, Bridle H, et al. Case-control study 

of familial lung cancer risks in UK women. Int J Cancer 

2005 Sep 1;116(3):445-50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Matalliotakis IM, Cakmak H, Mahutte N, et al. The familial 

risk of breast cancer in women with endometriosis from 

Yale series. Surg Oncol 2008 Dec;17(4):289-93. 

Excluded because no eligible outcomes presented 

Mateo J, Oliver A, Borrell M, et al. Laboratory evaluation 

and clinical characteristics of 2,132 consecutive unselected 

patients with venous thromboembolism - Results of the 

Spanish multicentric study on thrombophilia (EMETStudy). Thromb Haemost 1997;77(3):444-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Matsuura N, Fukuda K, Okuno A, et al. Descriptive 

epidemiology of IDDM in Hokkaido, Japan: The childhood 

IDDM Hokkaido Registry. Diabetes Care 

1998;21(10):1632-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mavale-Manuel S, Alexandre F, Duarte N, et al. Risk 

factors for asthma among children in Maputo 

(Mozambique). Allergy 2004;59(4):388-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mayne ST, Buenconsejo J, Janerich DT. Familial cancer 

history and lung cancer risk in United States nonsmoking 

men and women. Cancer Epidemiol Biomarkers Prev 

1999;8(12):1065-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McCahy PJ, Harris CA, Neal DE. Breast and prostate 

cancer in the relatives of men with prostate cancer. Br J 

Urol 1996 Oct;78(4):552-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McCann S, MacAuley D, Barnett Y. General practitioners 

and genes: Perceived roles, confidence and satisfaction 

with knowledge. E J Gen Pract 2002;8(4):140-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McCann S, MacAuley D, Barnett Y. Genetic consultations 

in primary care: GPs' responses to three scenarios. Scand J 

Prim Health Care 2005 Jun;23(2):109-14. 

Excluded because no eligible outcomes presented 

McClain MR, Palomaki GE, Hampel H, et al. Screen 

positive rates among six family history screening protocols 

for breast/ovarian cancer in four cohorts of women. Fam 

Cancer 2008;7(4):341-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McCredie M, Paul C, Skegg DC, et al. Family history and 

risk of breast cancer in New Zealand. Int J Cancer 1997 

Nov 14;73(4):503-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McCredie MR, Dite GS, Giles GG, et al. Breast cancer in 

Australian women under the age of 40. Cancer Causes 

Control 1998 Mar;9(2):189-98. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McCusker ME, Yoon PW, Gwinn M, et al. Family history 

of heart disease and cardiovascular disease risk-reducing 

behaviors. Genet Med 2004 May;6(3):153-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-44
and outcome criteria were met for the review questions in 

aggregate 

McGrath NM, Parker GN, Dawson P. Early presentation of 

type 2 diabetes mellitus in young New Zealand Maori. 

Diabetes Res Clin Pract 1999;43(3):205-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

McKinley AG, Russell SE, Spence RA, et al. Hereditary 

breast cancer in Northern Ireland. Ulster Med J 1996 

Nov;65(2):113-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Meeske K, Press M, Patel A, et al. Impact of reproductive 

factors and lactation on breast carcinoma in situ risk. Int J 

Cancer 2004;110(1):102-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mehdipour P, Atri M, Jafarimojarrad E, et al. Laddering 

through pedigrees: family history of malignancies in 

primary breast cancer patients. Asian Pac J Cancer Prev 

2003 Jul;4(3):185-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Melia J, Dearnaley D, Moss S, et al. The feasibility and 

results of a population-based approach to evaluating 

prostate-specific antigen screening for prostate cancer in 

men with a raised familial risk. Br J Cancer 2006 Feb 

27;94(4):499-506. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mellon S, Gold R, Janisse J, et al. Risk perception and 

cancer worries in families at increased risk of familial 

breast/ovarian cancer. Psychooncology 2008;17(8):756-66. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Menon VU, Kumar KV, Gilchrist A, et al. Prevalence of 

known and undetected diabetes and associated risk factors 

in central Kerala - ADEPS. Diabetes Res Clin Pract 

2006;74(3):289-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Menotti A, Giampaoli S. A single risk factor measurement 

predicts 35-year mortality from cardiovascular disease. G 

Ital Cardiol 1998;28(12):1354-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Menotti A, Lanti M, Maiani G, et al. Forty-year mortality 

from cardiovascular diseases and their risk factors in men 

of the Italian rural areas of the Seven Countries Study. Acta 

Cardiol 2005;60(5):521-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Menotti A, Lanti M, Maiani G, et al. Determinants of 

longevity and all-cause mortality among middle-aged men. 

Role of 48 personal characteristics in a 40-year follow-up 

of Italian Rural Areas in the Seven Countries Study. Aging 

Clin Exp Res 2006;18(5):394-406. 

Excluded because no eligible outcomes presented 

Merchant JA, Naleway AL, Svendsen ER, et al. Asthma 

and farm exposures in a cohort of rural Iowa children. 

Environ Health Perspect 2005;113(3):350-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Meschia JF, Case LD, Worrall BB, et al. Family history of 

stroke and severity of neurologic deficit after stroke. 

Neurology 2006 Oct 24;67(8):1396-402. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mete E, Erdemli K, Bavbek N, et al. High levels of cord 

serum eosinophil cationic protein predict the risk of atopy. 

J Asthma 2004;41(6):679-82. 

Excluded because no eligible outcomes presented 

Meunier J, Dorchy H, Luminet O. Does family 

cohesiveness and parental alexithymia predict glycaemic 

control in children and adolescents with diabetes? Diabetes 

Metab 2008;34(5):473-81. 

Excluded because no eligible outcomes presented 

Meyer P, Zuern C, Hermanns N, et al. The association 

between paternal prostate cancer and type 2 diabetes. J 

Carcinog 2007;6:14 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Milionis HJ, Kalantzi KJ, Papathanasiou AJ, et al. 

Metabolic syndrome and risk of acute coronary syndromes 

D-45
in patients younger than 45 years of age. Coron Artery Dis 

2007;18(4):247-52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mills PK, Riordan DG, Cress RD. Epithelial ovarian cancer 

risk by invasiveness and cell type in the Central Valley of 

California. Gynecol Oncol 2004;95(1):215-25. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Milne BJ, Moffitt TE, Crump R, et al. How should we 

construct psychiatric family history scores? A comparison 

of alternative approaches from the Dunedin Family Health 

History Study. Psychol Med 2008 Dec;38(12):1793-802. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Minami Y, Ohuchi N, Fukao A, et al. Risk factors for 

breast cancer: A case-control study of screen-detected 

breast cancer in Miyagi Prefecture, Japan. Breast Cancer 

Res Treat 1997;44(3):225-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mink PJ, Folsom AR, Sellers TA, et al. Physical activity, 

waist-to-hip ratio, and other risk factors for ovarian cancer: 

a follow-up study of older women. Epidemiology 1996 

Jan;7(1):38-45. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mirzaei F, Kazemi N. Prevalence of polycystic ovary 

syndrome in women with type 2 diabetes in Kerman, Iran. 

Metab Syndr Relat Disord 2008;6(3):215-7. 

Excluded because no eligible outcomes presented 

Mitchell BD, Zaccaro D, Wagenknecht LE, et al. Insulin 

sensitivity, body fat distribution, and family diabetes 

history: the IRAS Family Study. Obes Res 2004 

May;12(5):831-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mitsunobu F, Mifune T, Hosaki Y, et al. IgE-mediated and 

age-related bronchial hyperresponsiveness in patients with 

asthma. Relationship to family history of the disease. Age 

Ageing 2000 May;29(3):215-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Miyake Y, Tanaka K, Sasaki S, et al. Breastfeeding and the 

risk of wheeze and asthma in Japanese infants: The Osaka 

Maternal and Child Health Study. Pediatr Allergy Immunol 

2008;19(6):490-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Modugno F, Ness RB, Wheeler JE. Reproductive risk 

factors for epithelial ovarian cancer according to histologic 

type and invasiveness. Ann Epidemiol 2001;11(8):568-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Molino A, Giovannini M, Pedersini R, et al. Correlations 

between family history and cancer characteristics in 2256 

breast cancer patients. Br J Cancer 2004 Jul 5;91(1):96-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Moller P, Reis MM, Evans G, et al. Efficacy of early 

diagnosis and treatment in women with a family history of 

breast cancer. European Familial Breast Cancer 

Collaborative Group. Dis Markers 1999 Oct;15(1-3):179-

86. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Molyneaux L, Constantino M, Yue D. Strong family 

history predicts a younger age of onset for subjects 

diagnosed with type 2 diabetes. Diabetes Obes Metab 2004 

May;6(3):187-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Momiyama Y, Suzuki Y, Ohsuzu F, et al. Maternally 

transmitted susceptibility to non-insulin-dependent diabetes 

mellitus and left ventricular hypertrophy. J Am Coll 

Cardiol 1999 Apr;33(5):1372-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Montefort S, Lenicker HM, Caruna S, et al. Asthma, 

rhinitis and eczema in Maltese 13-15 year-old 

schoolchildren - Prevalence, severity and associated factors 

[ISAAC]. Clin Exp Allergy 1998;28(9):1089-99. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-46
and outcome criteria were met for the review questions in 

aggregate 

Montefort S, Muscat HA, Caruana S, et al. Allergic 

conditions in 5-8-year-old Maltese schoolchildren: 

Prevalence, severity, and associated risk factors [ISAAC]. 

Pediatr Allergy Immunol 2002;13(2):98-104. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Monti MC, Lonsdale JT, Montomoli C, et al. Familial risk 

factors for microvascular complications and differential 

male-female risk in a large cohort of American families 

with type 1 diabetes. J Clin Endocrinol Metab 2007 

Dec;92(12):4650-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Montnemery P, Adelroth E, Heuman K, et al. Prevalence of 

obstructive lung diseases and respiratory symptoms in 

southern Sweden. Respir Med 1998;92(12):1337-45. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Moore MM, Rifas-Shiman SL, Rich-Edwards JW, et al. 

Perinatal Predictors of Atopic Dermatitis Occurring in the 

First Six Months of Life. Pediatrics 2004;113(3 I):468-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mooy JM, Grootenhuis PA, de Vries H, et al. Prevalence 

and determinants of glucose intolerance in a Dutch 

Caucasian population: The Hoorn study. Diabetes Care 

1995;18(9):1270-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mori M, Nishida T, Sugiyama T, et al. Anthropometric and 

other risk factors for ovarian cancer in a case-control study. 

Jpn J Cancer Res 1998 Mar;89(3):246-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Morris L, Taylor M, Campbell LM, et al. How will 

practices cope with information for the new GMS contract? 

Coronary heart disease data recording in five Scottish 

practices. Inform Prim Care 2003;11(3):121-7. 

Excluded because no eligible outcomes presented 

Morris MC, Ciesla JA, Garber J. A prospective study of the 

cognitive-stress model of depressive symptoms in 

adolescents. J Abnorm Psychol 2008 Nov;117(4):719-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Morrison JA, Friedman LA, Wang P, et al. Metabolic 

Syndrome in Childhood Predicts Adult Metabolic 

Syndrome and Type 2 Diabetes Mellitus 25 to 30 Years 

Later. J Pediatr 2008;152(2):201-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Moses R, Rodda M, Griffiths R. Predominance of a 

maternal history of diabetes for patients with non-insulinindependent diabetes mellitus. Implications for the 

intrauterine transmission of diabetes. Aust N Z J Obstet 

Gynaecol 1997;37(3):279-81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Moskowitz WB, Schwartz PF, Schieken RM. Childhood 

passive smoking, race, and coronary artery disease risk: 

The MCV twin study. Arch Pediatr Adolesc Med 

1999;153(5):446-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mouchawar J, Klein CE, Mullineaux L. Colorado family 

physicians' knowledge of hereditary breast cancer and 

related practice. J Cancer Educ 2001;16(1):33-7. 

Excluded because family history not collected 

Mourad M, Levendosky A, Bogat GA, et al. Family 

psychopathology and perceived stress of both domestic 

violence and negative life events as predictors of women's 

mental health symptoms. J Fam Violence 2008 

Nov;23(8):661-70. 

Excluded because not an eligible population 

Moussa MAA, Alsaeid M, Refai TMK, et al. Factors 

associated with type 1 diabetes in Kuwaiti children. Acta 

Diabetol 2005;42(3):129-37. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Moussa MAA, Alsaeid M, Abdella N, et al. Prevalence of 

type 2 diabetes mellitus among Kuwaiti children and 

adolescents. Med Princ Pract 2008;17(4):270-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-47
and outcome criteria were met for the review questions in 

aggregate 

Mrena S, Virtanen SM, Laippala P, et al. Models for 

predicting type 1 diabetes in siblings of affected children. 

Diabetes Care 2006 Mar;29(3):662-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Murff HJ, Byrne D, Syngal S. Cancer risk assessment: 

quality and impact of the family history interview. Am J 

Prev Med 2004 Oct;27(3):239-45. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Murff HJ, Peterson NB, Greevy R, et al. Impact of patient 

age on family cancer history. Genet Med 2006 

Jul;8(7):438-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Murff HJ, Greevy RA, Syngal S. The comprehensiveness 

of family cancer history assessments in primary care. 

Community Genet 2007;10(3):174-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Murgia C, Berria R, Minerba L, et al. Risk assessment does 

not explain high prevalence of gestational diabetes mellitus 

in a large group of Sardinian women. Reprod Biol 

Endocrinol 2008;6:26 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Mursu J, Voutilainen S, Nurmi T, et al. Flavonoid intake 

and the risk of ischaemic stroke and CVD mortality in 

middle-aged Finnish men: The Kuopio Ischaemic Heart 

Disease Risk Factor Study. Br J Nutr 2008;100(4):890-5. 

Excluded because no eligible outcomes presented 

Murta-Nascimento C, Silverman DT, Kogevinas M, et al. 

Risk of bladder cancer associated with family history of 

cancer: do low-penetrance polymorphisms account for the 

increase in risk? Cancer Epidemiol Biomarkers Prev 2007 

Aug;16(8):1595-600. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Myers CD, Jacobsen PB, Huang Y, et al. Familial and 

perceived risk of breast cancer in relation to use of 

complementary medicine. Cancer Epidemiol Biomarkers 

Prev 2008;17(6):1527-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Naff JL, Cote ML, Wenzlaff AS, et al. Racial differences in 

cancer risk among relatives of patients with early onset 

lung cancer. Chest 2007 May;131(5):1289-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Naheed F, Kammeruddin K, Hashmi HA, et al. Frequency 

of impaired oral glucose tolerance test in high risk 

pregnancies for gestational diabetes mellitus. J Coll 

Physicians Surg Pak 2008;18(2):82-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nakama H, Zhang B, Fukazawa K, et al. Family history of 

colorectal adenomatous polyps as a risk factor for 

colorectal cancer. Eur J Cancer 2000 Oct;36(16):2111-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nakama H, Fukazawa K. Colorectal cancer risk in firstdegree relatives of patients with colorectal adenomatous 

polyp. Hepatogastroenterology 2002 Jan;49(43):157-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nam RK, Toi A, Klotz LH, et al. Assessing individual risk 

for prostate cancer. J Clin Oncol 2007;25(24):3582-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nandkeoliar MK, Dharmalingam M, Marcus SR. Diabetes 

mellitus in Asian Indian children and adolescents. J Pediatr 

Endocrinol Metab 2007;20(10):1109-14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nasir K, Michos ED, Rumberger JA, et al. Coronary artery 

calcification and family history of premature coronary heart 

disease: sibling history is more strongly associated than 

parental history. Circulation 2004 Oct 12;110(15):2150-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-48
and outcome criteria were met for the review questions in 

aggregate 

Nasir K, Budoff MJ, Wong ND, et al. Family history of 

premature coronary heart disease and coronary artery 

calcification: Multi-Ethnic Study of Atherosclerosis 

(MESA). Circulation 2007 Aug 7;116(6):619-26. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Negri E, Braga C, La Vecchia C, et al. Family history of 

cancer and risk of breast cancer. Int J Cancer 1997 Sep 

4;72(5):735-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Negri E, Braga C, La Vecchia C, et al. Family history of 

cancer and risk of colorectal cancer in Italy. Br J Cancer 

1998;77(1):174-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Negri E, Pelucchi C, Franceschi S, et al. Family history of 

cancer and risk of ovarian cancer. Eur J Cancer 2003 

Mar;39(4):505-10. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Negri E, Pelucchi C, Talamini R, et al. Family history of 

cancer and the risk of prostate cancer and benign prostatic 

hyperplasia. Int J Cancer 2005 Apr 20;114(4):648-52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Negri E, Foschi R, Talamini R, et al. Family history of 

cancer and the risk of renal cell cancer. Cancer Epidemiol 

Biomarkers Prev 2006 Dec;15(12):2441-4. 

Excluded because no eligible outcomes presented 

Neise C, Rauchfuss M, Paepke S, et al. Risk perception and 

psychological strain in women with a family history of 

breast cancer. Onkologie 2001 Oct;24(5):470-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nelson T, Perez A, Alcaraz J, et al. Family history of 

diabetes, acculturation, and the metabolic syndrome among 

Mexican Americans: Proyecto SALSA. Metab Syndr Relat 

Disord 2007;5(3):262-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nemesure B, Wu SY, Hambleton IR, et al. Risk factors for 

breast cancer in a black population--the Barbados National 

Cancer Study. Int J Cancer 2009 Jan 1;124(1):174-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ness RB, Markovic N, Bass D, et al. Family history of 

hypertension, heart disease, and stroke among women who 

develop hypertension in pregnancy. Obstet Gynecol 2003 

Dec;102(6):1366-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Newcomb PA, Taylor JO, Trentham-Dietz A. Interactions 

of familial and hormonal risk factors for large bowel cancer 

in women. Int J Epidemiol 1999 Aug;28(4):603-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nicolaou M, DeStefano AL, Gavras I, et al. Genetic 

predisposition to stroke in relatives of hypertensives. Stroke 

2000 Feb;31(2):487-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nilsson PM, Nilsson J-A, Berglund G. Family burden of 

cardiovascular mortality: Risk implications for offspring in 

a national register linkage study based upon the Malmo 

Preventive Project. J Intern Med 2004;255(2):229-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nishigaki M, Kobayashi K, Hitomi T, et al. Perception of 

offspring risk for type 2 diabetes among patients with type 

2 diabetes and their adult offspring. Diabetes Care 

2007;30(12):3033-4. 

Excluded because no eligible outcomes presented 

Nishigaki M, Kobayashi K, Kato N, et al. Preventive 

advice given by patients with type 2 diabetes to their 

offspring. Br J Gen Pract 2009 Jan;59(558):37-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-49
Nishtar S, Wierzbicki AS, Lumb PJ, et al. Waist-hip ratio 

and low HDL predict the risk of coronary artery disease in 

Pakistanis. Curr Med Res Opin 2004;20(1):55-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nitadori J, Inoue M, Iwasaki M, et al. Association between 

lung cancer incidence and family history of lung cancer: 

data from a large-scale population-based cohort study, the 

JPHC study. Chest 2006 Oct;130(4):968-75. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nixon RM, Pharoah P, Tabar L, et al. Mammographic 

screening in women with a family history of breast cancer: 

some results from the Swedish two-county trial. Rev 

Epidemiol Sante Publique 2000 Aug;48(4):325-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

No ai. Promoting physical activity in an at-risk population. 

J Sport Exerc Psychol 2008 Jun;30(3):434 

Excluded because not an eligible study design 

Norman P, Brain K. An application of an extended health 

belief model to the prediction of breast self-examination 

among women with a family history of breast cancer. Br J 

Health Psychol 2005 Feb;10(Pt:1):1-16. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Norrman E, Nystrom L, Jonsson E, et al. Prevalence and 

incidence of asthma and rhinoconjunctivitis in Swedish 

teenagers. Allergy 1998 Jan;53(1):28-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Norsa'adah B, Rusli BN, Imran AK, et al. Risk factors of 

breast cancer in women in Kelantan, Malaysia. Singapore 

Med J 2005 Dec;46(12):698-705. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nuhu FT, Odejide OA, Adebayo KO, et al. Prevalence and 

predictors of depression in cancer patients in the University 

College Hospital Ibadan, Nigeria. Hong Kong J Psychiatry 

2008;18(3):107-14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Nwose EU, Richards RS, Kerr PG, et al. Oxidative damage 

indices for the assessment of subclinical diabetic 

macrovascular complications. Br J Biomed Sci 

2008;65(3):136-41. 

Excluded because no eligible outcomes presented 

O'Neil JN, Emery CF. Psychosocial vulnerability, hostility, 

and family history of coronary heart disease among male 

and female college students. Int J Behav Med 

2002;9(1):17-36. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

O'Sullivan B, McGee H, Keegan O. Comparing solutions to 

the 'expectancy-value muddle' in the theory of planned 

behaviour. Br J Health Psychol 2008;13(4):789-802. 

Excluded because family history not collected 

Ockhuysen-Vermey CF, Henneman L, van Asperen CJ, et 

al. Design of the BRISC study: A multicentre controlled 

clinical trial to optimize the communication of breast 

cancer risks in genetic counselling. BMC Cancer 

2008;8:283. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ogonowski J, Miazgowski T, Homa K, et al. Low 

predictive value of traditional risk factors in identifying 

women at risk for gestational diabetes. Acta Obstet 

Gynecol Scand 2007;86(10):1165-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ohaeri JU, Otote DI. Family history, life events and the 

factorial structure of depression in a Nigerian sample of 

inpatients. Psychopathology 2002 Jul;35(4):210-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ohannessian CM, Hesselbrock VM. Predictors of substance 

abuse and affective diagnosis: Does having a family history 

of alcoholism make a difference? Appl Dev Sci 

1999;3(4):239-47. 

Excluded because no eligible outcomes presented 

Okamoto K, Horisawa R, Kawamura T, et al. Family 

history and risk of subarachnoid hemorrhage: a casecontrol study in Nagoya, Japan. Stroke 2003 

Feb;34(2):422-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-50
and outcome criteria were met for the review questions in 

aggregate 

Oldak E, Kurzatkowska B, Stasiak-Barmuta A. Natural 

course of sensitization in children: follow-up study from 

birth to 6 years of age, I. Evaluation of total serum IgE and 

specific IgE antibodies with regard to atopic family history. 

Rocz Akad Med Bialymst 2000;45:87-95. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Olesen AB, Ellingsen AR, Olesen H, et al. Atopic 

dermatitis and birth factors: historical follow up by record 

linkage. BMJ 1997 Apr 5;314(7086):1003-8. 

Excluded because no eligible outcomes presented 

Oleske DM, Galvez A, Cobleigh MA, et al. Are tri-ethnic 

low-income women with breast cancer effective teachers of 

the importance of breast cancer screening to their firstdegree relatives? Results from a randomized clinical trial. 

Breast J 2007 Jan;13(1):19-27. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Oliveira JEP, Milech A, Franco LJ. The prevalence of 

diabetes in Rio de Janeiro, Brazil. Diabetes Care 

1996;19(6):663-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Olson JE, Sellers TA, Iturria SJ, et al. Bilateral 

oophorectomy and breast cancer risk reduction among 

women with a family history. Cancer Detect Prev 

2004;28(5):357-60. 

Excluded because family history not collected 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Olsson H, Bladstrom A. A cohort study of reproductive 

factors and family history of breast cancer in southern 

Sweden. Breast Cancer Res Treat 2002 Dec;76(3):203-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Omar MA, Motala AA, Seedat MA, et al. The significance 

of a positive family history in South African Indians with 

non-insulin-dependent diabetes (NIDDM). Diabetes Res 

Clin Pract 1996 Oct;34:S13-S16 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Omland O, Sigsgaard T, Hjort C, et al. Lung status in 

young Danish rurals: The effect of farming exposure on 

asthma-like symptoms and lung function. Eur Respir J 

1999;13(1):31-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Orom H, Cote ML, Gonzalez HM, et al. Family history of 

cancer: is it an accurate indicator of cancer risk in the 

immigrant population? Cancer 2008 Jan 15;112(2):399-

406. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Othmer E, DeSouza CM, Penick EC, et al. Indicators of 

mania in depressed outpatients: A retrospective analysis of 

data from the Kansas 1500 study. J Clin Psychiatry 

2007;68(1):47-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ott C, Obermeier F, Thieler S, et al. The incidence of 

inflammatory bowel disease in a rural region of Southern 

Germany: a prospective population-based study. Eur J 

Gastroenterol Hepatol 2008 Sep;20(9):917-23. 

Excluded because no eligible outcomes presented 

Ozaki R, Qiao Q, Wong GW, et al. Overweight, family 

history of diabetes and attending schools of lower academic 

grading are independent predictors for metabolic syndrome 

in Hong Kong Chinese adolescents. Arch Dis Child 2007 

Mar;92(3):224-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Paek KW, Chun KH, Lee KW. Relationship between 

metabolic syndrome and familial history of 

hypertension/stroke, diabetes, and cardiovascular disease. J 

Korean Med Sci 2006 Aug;21(4):701-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Page WF, Braun MM, Partin AW, et al. Heredity and 

prostate cancer: A study of world war II veteran twins. 

Prostate 1997;33(4):240-5. 

Excluded because family history not collected 

Pakhale S, Wooldrage K, Manfreda J, et al. Prevalence of 

asthma symptoms in 7th- and 8th-grade school children in a 

rural region in India. J Asthma 2008;45(2):117-22. 

D-51
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pal T, Vadaparampil S, Betts J, et al. BRCA1/2 in high-risk 

African American women with breast cancer: Providing 

genetic testing through various recruitment strategies. 

Genet Test 2008;12(3):401-7. 

Excluded because no eligible outcomes presented 

Pala K, Aksu H. Prevalence and associated risk factors of 

type 2 diabetes mellitus in Nilufer District, Bursa, Turkey. 

Int J Diabetes Metabol 2006;14(2):98-102. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pallasaho P, Lundback B, Laspa SL, et al. Increasing 

prevalence of asthma but not of chronic bronchitis in 

Finland? Report from the FinEsS-Helsinki study. Respir 

Med 1999;93(11):798-809. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Palomaki GE, McClain MR, Steinort K, et al. Screenpositive rates and agreement among six family history 

screening protocols for breast/ovarian cancer in a 

population-based cohort of 21- to 55-year-old women. 

Genet Med 2006 Mar;8(3):161-8. 

Excluded because no eligible outcomes presented 

Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. Risk 

stratification of coronary heart disease in Greece: Final 

results from the CARDIO2000 epidemiological study. Prev 

Med 2002;35(6):548-56. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. An 

integrated assessment of family history on the risk of 

developing acute coronary syndromes (CARDIO2000 

study). Acta Cardiol 2004 Aug;59(4):383-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Panagiotakos DB, Pitsavos C, Skoumas Y, et al. Five-year 

incidence of type 2 diabetes mellitus among cardiovascular 

disease-free Greek adults: Findings from the ATTICA 

study. Vasc Health Risk Manag 2008;4(3):691-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. 

Hierarchical analysis of cardiovascular risk factors in 

relation to the development of acute coronary syndromes, 

in different parts of Greece: The CARDIO2000 study. 

Angiology 2008;59(2):156-65. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Panagiotakos DB, Pitsavos C, Skoumas Y, et al. Five-year 

incidence of type 2 diabetes mellitus among cardiovascular 

disease-free Greek adults: Findings from the ATTICA 

study. Vasc Health Risk Manag 2008;4(3):691-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Panikar VK, Joshi SR, Kakraniya P, et al. Inter-generation 

comparison of type-2 diabetes in 73 Indian families. J 

Assoc Physicians India 2008 Aug;56:601-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pannacciulli N, De Pergola G, Ciccone M, et al. Effect of 

family history of type 2 diabetes on the intima-media 

thickness of the common carotid artery in normal-weight, 

overweight, and obese glucose-tolerant young adults. 

Diabetes Care 2003 Apr;26(4):1230-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Parent ME, Ghadirian P, Lacroix A, et al. The reliability of 

recollections of family history: implications for the medical 

provider. J Cancer Educ 1997;12(2):114-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Parikh NI, Hwang SJ, Larson MG, et al. Parental 

occurrence of premature cardiovascular disease predicts 

increased coronary artery and abdominal aortic 

calcification in the Framingham Offspring and Third 

Generation cohorts. Circulation 2007 Sep 25;116(13):1473-

81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Parikh NI, Hwang SJ, Yang Q, et al. Clinical correlates and 

heritability of cystatin C (from the Framingham Offspring 

Study). Am J Cardiol 2008 Nov 1;102(9):1194-8. 

Excluded because family history not collected 

D-52
Park HS, Kim SM, Lee JS, et al. Prevalence and trends of 

metabolic syndrome in Korea: Korean National Health and 

Nutrition Survey 1998-2001. Diabetes Obes Metab 

2007;9(1):50-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Park JW, Yun JE, Park T, et al. Family history of diabetes 

and risk of atherosclerotic cardiovascular disease in Korean 

men and women. Atherosclerosis 2008 Mar;197(1):224-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Partin MR, Burgess DJ, Halek K, et al. Randomized trial 

showed requesting medical records with a survey produced 

a more representative sample than requesting separately. J 

Clin Epidemiol 2008;61(10):1028-35. 

Excluded because no eligible outcomes presented 

Parvez T, Anwar MS, Sheikh AM. Study of risk factors for 

carcinoma breast in adult female general population in 

Lahore. J Coll Physicians Surg Pak 2001;11(5):291-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pascale RW, Wing RR, Butler BA, et al. Effects of a 

behavioral weight loss program stressing calorie restriction 

versus calorie plus fat restriction in obese individuals with 

NIDDM or a family history of diabetes. Diabetes Care 

1995 Sep;18(9):1241-8. 

Excluded because no eligible outcomes presented 

Pasquarella A, Buonomo E, Carbini R, et al. Family history 

of cardiovascular diseases and risk factors in children. J 

Hum Hypertens 1996 Sep;10(Suppl 3):S107-109 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Patel MJ, de Lemos JA, Philips B, et al. Implications of 

family history of myocardial infarction in young women. 

Am Heart J 2007 Sep;154(3):454-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Patenaude AF, Orozco S, Li X, et al. Support needs and 

acceptability of psychological and peer consultation: 

Attitudes of 108 women who had undergone or were 

considering prophylactic mastectomy. Psychooncology 

2008 Aug;17(8):831-43. 

Excluded because no eligible outcomes presented 

Pazarloglou M, Spaia S, Pagkalos E, et al. Evaluation of 

insulin resistance and sodium sensitivity in normotensive 

offspring of hypertensive individuals. Am J Kidney Dis 

2007 Apr;49(4):540-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pearson JD, Lei HH, Beaty TH, et al. Familial aggregation 

of bothersome benign prostatic hyperplasia symptoms. 

Urology 2003 Apr;61(4):781-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pelucchi C, Galeone C, Talamini R, et al. Lifetime 

ovulatory cycles and ovarian cancer risk in 2 Italian casecontrol studies. Am J Obstet Gynecol 2007;196(1):83 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pereira MA, Schreiner PJ, Pankow JS, et al. The Family 

Risk Score for coronary heart disease: associations with 

lipids, lipoproteins, and body habitus in a middle-aged biracial cohort: The ARIC study. Ann Epidemiol 2000 

May;10(4):239-45. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pereira MU, Sly PD, Pitrez PM, et al. Nonatopic asthma is 

associated with helminth infections and bronchiolitis in 

poor children. Eur Respir J 2007;29(6):1154-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Perez LH, Gutierrez LA, Vioque J, et al. Relation between 

overweight, diabetes, stress and hypertension: A casecontrol study in Yarumal - Antioquia, Colombia. Eur J 

Epidemiol 2001;17(3):275-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Perlis RH, Brown E, Baker RW, et al. Clinical features of 

bipolar depression versus major depressive disorder in 

large multicenter trials. Am J Psychiatry 2006;163(2):225-

31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-53
Pesonen M, Kallio MJT, Ranki A, et al. Prolonged 

exclusive breastfeeding is associated with increased atopic 

dermatitis: A prospective follow-up study of unselected 

healthy newborns from birth to age 20 years. Clin Exp 

Allergy 2006;36(8):1011-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Peters CA, Stock RG, Blacksburg SR, et al. Effect of 

family history on outcomes in patients treated with 

definitive brachytherapy for clinically localized prostate 

cancer. Int J Radiat Oncol Biol Phys 2009 Jan 1;73(1):24-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Petersen GM, Larkin E, Codori AM, et al. Attitudes toward 

colon cancer gene testing: survey of relatives of colon 

cancer patients. Cancer Epidemiol Biomarkers Prev 1999 

Apr;8(4:Pt 2):337-44. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Petrisek A, Campbell S, Laliberte L. Family history of 

breast cancer: impact on the disease experience. Cancer 

Pract 2000 May;8(3):135-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pharoah PD, Lipscombe JM, Redman KL, et al. Familial 

predisposition to breast cancer in a British population: 

implications for prevention. Eur J Cancer 2000 

Apr;36(6):773-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Philips B, de Lemos JA, Patel MJ, et al. Relation of family 

history of myocardial infarction and the presence of 

coronary arterial calcium in various age and risk factor 

groups. Am J Cardiol 2007 Mar 15;99(6):825-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Phillips KA, Butow PN, Stewart AE, et al. Predictors of 

participation in clinical and psychosocial follow-up of the 

kConFab breast cancer family cohort. Fam Cancer 

2005;4(2):105-13. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Phillips KL, An P, Boyd JH, et al. Major gene effect and 

additive familial pattern of inheritance of asthma exist 

among families of probands with sickle cell anemia and 

asthma. Am J Human Biol 2008 Mar;20(2):149-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pierce M, Harding D, Ridout D, et al. Risk and prevention 

of type II diabetes: offspring's views. Br J Gen Pract 2001 

Mar;51(464):194-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pinol V, Andreu M, Castells A, et al. Synchronous 

colorectal neoplasms in patients with colorectal cancer: 

predisposing individual and familial factors. Dis Colon 

Rectum 2004 Jul;47(7):1192-200. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Piver MS, Goldberg JM, Tsukada Y, et al. Characteristics 

of familial ovarian cancer: a report of the first 1,000 

families in the Gilda Radner Familial Ovarian Cancer 

Registry. Eur J Gynaecol Oncol 1996;17(3):169-76. 

Excluded because no eligible outcomes presented 

Pohjola-Sintonen S, Rissanen A, Liskola P, et al. Family 

history as a risk factor of coronary heart disease in patients 

under 60 years of age. Eur Heart J 1998 Feb;19(2):235-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Polednak AP, Flannery JT. Family history of breast and 

ovarian cancer among breast-cancer patients in the 

Connecticut Tumor Registry. Conn Med 1996 

Feb;60(2):67-73. 

Excluded because no eligible outcomes presented 

Polley BA, Jakicic JM, Venditti EM, et al. The effects of 

health beliefs on weight loss in individuals at high risk for 

NIDDM. Diabetes Care 1997;20(10):1533-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Polosa R, Al Delaimy WK, Russo C, et al. Greater risk of 

incident asthma cases in adults with allergic rhinitis and 

effect of allergen immunotherapy: A retrospective cohort 

study. Respir Res 2005 Dec 28;6:153. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-54
and outcome criteria were met for the review questions in 

aggregate 

Polychronopoulos P, Gioldasis G, Ellul J, et al. Family 

history of stroke in stroke types and subtypes. J Neurol Sci 

2002 Mar 30;195(2):117-22. 

Excluded because not an eligible population 

Ponder M, Lee J, Green J, et al. Family history and 

perceived vulnerability to some common diseases: A study 

of young people and their parents. J Med Genet 

1996;33(6):485-92. 

Excluded because no eligible outcomes presented 

Poole CA, Byers T, Calle EE, et al. Influence of a family 

history of cancer within and across multiple sites on 

patterns of cancer mortality risk for women. Am J 

Epidemiol 1999;149(5):454-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Portengen L, Sigsgaard T, Omland O, et al. Low 

prevalence of atopy in young danish farmers and farming 

students born and raised on a farm. Clin Exp Allergy 

2002;32(2):247-53. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pottier P, Cormier G, Truchaud F, et al. Efficiency of 

systematic thrombophilia screening in idiopathic venous 

thrombosis: A prospective study in internal medicine. Clin 

Appl Thromb Hemost 2005;11(3):243-51. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pratt CA, Ha L, Levine SR, et al. Stroke Knowledge and 

Barriers to Stroke Prevention Among African Americans: 

Implications for Health Communication. J Health Commun 

2003 Jul;8(4):369-81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Pravin D, Malhotra S, Chakrabarti S, et al. Frequency of 

major affective disorders in first-degree relatives of patients 

with type 2 diabetes mellitus. Indian J Med Res 2006 

Sep;124(3):291-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Purdie D, Green A, Bain C, et al. Reproductive and other 

factors and risk of epithelial ovarian cancer: an Australian 

case-control study. Survey of Women's Health Study 

Group. Int J Cancer 1995 Sep 15;62(6):678-84. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Purvis DJ, Thompson JM, Clark PM, et al. Risk factors for 

atopic dermatitis in New Zealand children at 3.5 years of 

age. Br J Dermatol 2005 Apr;152(4):742-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Quillin JM, Ramakrishnan V, Borzelleca J, et al. Paternal 

relatives and family history of breast cancer. Am J Prev 

Med 2006 Sep;31(3):265-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Quillin JM, Bodurtha JN, McClish DK, et al. The effect of 

a school-based educational intervention on gender 

differences in reported family cancer history. J Cancer 

Educ 2008;23(3):180-5. 

Excluded because no eligible outcomes presented 

Quillin JM, Silberg J, Jones RM, et al. Tolerance for 

ambiguity could influence awareness of breast cancer 

genetic testing and inform health education. Cancer Causes 

Control 2008 Dec;19(10):1227-32. 

Excluded because no eligible outcomes presented 

Qureshi N, Kai J. Informing patients of familial diabetes 

mellitus risk: How do they respond? A cross-sectional 

survey. BMC Health Serv Res 2008;8:37. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Raby BA, Van Steen K, Celedon JC, et al. Paternal history 

of asthma and airway responsiveness in children with 

asthma. Am J Respir Crit Care Med 2005 Sep 

1;172(5):552-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rader JS, Neuman RJ, Brady J, et al. Cancer among firstdegree relatives of probands with invasive and borderline 

ovarian cancer. Obstet Gynecol 1998 Oct;92(4:Pt 1):589-

595. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-55
Radzikowska E, Roszkowski K, Glaz P. Lung cancer in 

patients under 50 years old. Lung Cancer 2001;33(2-

3):203-11. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rafter N, Wells S, Stewart A, et al. Gaps in primary care 

documentation of cardiovascular risk factors. N Z Med J 

2008;121(1269):24-33. 

Excluded because no eligible outcomes presented 

Ram R, Goswami DN, Bhattacharya SK, et al. An 

epidemiological study on risk factors of diabetes mellitus 

among patients attending a Medical College Hospital in 

Kolkata, West Bengal. J Indian Med Assoc 

2006;104(8):428-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ramachandran A, Snehalatha C, Mukesh B, et al. Persistent 

impaired glucose tolerance has similar rate of risk factors 

as for diabetes-Results of Indian Diabetes Prevention 

Programme (IDPP). Diabetes Res Clin Pract 

2006;73(1):100-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ramachandran A, Mary S, Yamuna A, et al. High 

prevalence of diabetes and cardiovascular risk factors 

associated with urbanization in India. Diabetes Care 2008 

May;31(5):893-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ramji F, Cotterchio M, Manno M, et al. Association 

between subject factors and colorectal cancer screening 

participation in Ontario, Canada. Cancer Detect Prev 

2005;29(3):221-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ramsey SD, Clarke L, Etzioni R, et al. Cost-effectiveness 

of microsatellite instability screening as a method for 

detecting hereditary nonpolyposis colorectal cancer. Ann 

Intern Med 2001 Oct 16;135(8:Pt 1):577-88. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ramsey SD, Burke W, Pinsky L, et al. Family history 

assessment to detect increased risk for colorectal cancer: 

conceptual considerations and a preliminary economic 

analysis. Cancer Epidemiol Biomarkers Prev 2005 

Nov;14(11:Pt 1):2494-2500. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Randi G, Pelucchi C, Negri E, et al. Family history of 

urogenital cancers in patients with bladder, renal cell and 

prostate cancers. Int J Cancer 2007 Dec 15;121(12):2748-

52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ranjith N, Verho NK, Verho M, et al. Acute myocardial 

infarction in a young South African Indian-based 

population: Patient characteristics on admission and 

gender-specific risk factor prevalence. Curr Med Res Opin 

2002;18(4):242-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ranjith N, Pegoraro RJ, Naidoo DP. Demographic data and 

outcome of acute coronary syndrome in the South African 

Asian Indian population. Cardiovasc J S Afr 

2005;16(1):48-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rankow EJ, Tessaro I. Mammography and risk factors for 

breast cancer in lesbian and bisexual women. Am J Health 

Behav 1998 Nov;22(6):403-10. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rasouli N, Spencer HJ, Rashidi AA, et al. Impact of family 

history of diabetes and ethnicity on -cell function in obese, 

glucose-tolerant individuals. J Clin Endocrinol Metab 2007 

Dec;92(12):4656-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rauscher GH, Sandler DP. Validating cancer histories in 

deceased relatives. Epidemiology 2005 Mar;16(2):262-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rawal R, Bertelsen L, Olsen JH. Cancer incidence in firstdegree relatives of a population-based set of cases of earlyD-56
onset breast cancer. Eur J Cancer 2006 Nov;42(17):3034-

40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rawl SM, Champion VL, Scott LL, et al. A randomized 

trial of two print interventions to increase colon cancer 

screening among first-degree relatives. Patient Educ Couns 

2008;71(2):215-27. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rebbeck TR, Turner ST, Sing CF. Probability of having 

hypertension: Effects of sex, history of hypertension in 

parents, and other risk factors. J Clin Epidemiol 

1996;49(7):727-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Reed T, Carmelli D, Swan GE, et al. Ten-year follow-up 

for male twins divided into high- or low-risk groups for 

ischemic heart disease based on risk factors measured 25 

years previously. Ann Epidemiol 2000;10(5):278-84. 

Excluded because no eligible outcomes presented 

Reinherz HZ, Giaconia RM, Hauf AMC, et al. General and 

specific childhood risk factors for depression and drug 

disorders by early adulthood. J Am Academy Child 

Adolesc Psychiatry 2000 Feb;39(2):223-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rende R, Birmaher B, Axelson D, et al. Psychotic 

symptoms in pediatric bipolar disorder and family history 

of psychiatric illness. J Affect Disord 2006 Nov;96(1-

2):127-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Retnakaran R, Connelly PW, Sermer M, et al. The impact 

of family history of diabetes on risk factors for gestational 

diabetes. Clin Endocrinol (Oxf) 2007 Nov;67(5):754-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Robb KA, Miles A, Wardle J. Demographic and 

psychosocial factors associated with perceived risk for 

colorectal cancer. Cancer Epidemiol Biomarkers Prev 

2004;13(3):366-72. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Robinson RF, Batisky DL, Hayes JR, et al. Body mass 

index in primary and secondary pediatric hypertension. 

Pediatr Nephrol 2004;19(12):1379-84. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rodriguez C, Plasencia A, Schroeder DG. Predictive 

factors of enrollment and adherence in a breast cancer 

screening program in Barcelona (Spain). Soc Sci Med 

1995;40(8):1155-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rodriguez C, Calle EE, Tatham LM, et al. Family history 

of breast cancer as a predictor for fatal prostate cancer. 

Epidemiology 1998 Sep;9(5):525-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Roglic G, Colhoun HM, Stevens LK, et al. Parental history 

of hypertension and parental history of diabetes and 

microvascular complications in insulin-dependent diabetes 

mellitus: the EURODIAB IDDM Complications Study. 

Diabet Med 1998 May;15(5):418-26. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rohrer J, Rohland B, Denison A, et al. Family history of 

mental illness and frequent mental distress in community 

clinic patients. J Eval Clin Pract 2007 Jun;13(3):435-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Roncaglioni MC, Avanzini F, Roccatagliata D, et al. How 

general pratitioners perceive and grade the cardiovascular 

risk of their patients. Eur J Cardiovasc Prev Rehabil 

2004;11(3):233-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ronco AL, De Stefani E, Boffetta P, et al. Food patterns 

and risk of breast cancer: A factor analysis study in 

Uruguay. Int J Cancer 2006;119(7):1672-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-57
and outcome criteria were met for the review questions in 

aggregate 

Ronmark E, Lundback B, Jonsson E, et al. Incidence of 

asthma in adults - Report from the obstructive lung disease 

in Northern Sweden study. Allergy 1997;52(11):1071-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ronmark E, Lundback B, Jonsson E, et al. Asthma, type-1 

allergy and related conditions in 7- and 8-year-old children 

in Northern Sweden: Prevalence rates and risk factor 

pattern. Respir Med 1998;92(2):316-24. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rose PW, Watson E, Yudkin P, et al. Referral of patients 

with a family history of breast/ovarian cancer--GPs' 

knowledge and expectations. Fam Pract 2001 

Oct;18(5):487-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rose PW, Murphy M, Munafo M, et al. Improving the 

ascertainment of families at high risk of colorectal cancer: a 

prospective GP register study. Br J Gen Pract 2004 

Apr;54(501):267-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rosenbaum M, Nonas C, Horlick M, et al. beta-Cell 

function and insulin sensitivity in early adolescence: 

association with body fatness and family history of type 2 

diabetes mellitus. J Clin Endocrinol Metab 2004 

Nov;89(11):5469-76. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Roumier X, Azzouzi R, Valeri A, et al. Adherence to an 

annual PSA screening program over 3 years for brothers 

and sons of men with prostate cancer. Eur Urol 

2003;45(3):280-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Roux C, Fardellone P, Lespessailles E, et al. Prevalence of 

risk factors for referring post-menopausal women for bone 

densitometry. The INSTANT study. Joint, Bone, Spine 

2008 Dec;75(6):702-7. 

Excluded because no eligible outcomes presented 

Rowe MG, Fleming MF, Barry KL, et al. Correlates of 

depression in primary care. J Fam Pract 1995;41(6):551-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Royak-Schaler R, Klabunde CN, Greene WF, et al. 

Communicating breast cancer risk: patient perceptions of 

provider discussions. Medscape Womens Health 

2002;7(2):2 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Rubin DT, LoSavio A, Yadron N, et al. Aminosalicylate 

Therapy in the Prevention of Dysplasia and Colorectal 

Cancer in Ulcerative Colitis. Clin Gastroenterol Hepatol 

2006;4(11):1346-50. 

Excluded because no eligible outcomes presented 

Rumboldt M, Rumboldt Z, Pesenti S. Premature parental 

heart attack is heralding elevated risk in their offspring. 

Coll Antropol 2003 Jun;27(1):221-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ruo L, Cellini C, La Calle JP, Jr., et al. Limitations of 

family cancer history assessment at initial surgical 

consultation. Dis Colon Rectum 1999 Apr;44(1):98-103. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Russell MB, Fenger K, Olesen J. The family history of 

migraine. Direct versus indirect information. Cephalalgia 

1996 May;16(3):156-60. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ryabikov A, Malyutina S, Ryabikov M, et al. Intrafamilial 

correlations of carotid intima-media thickness and flowmediated dilation in a Siberian population. Am J Hypertens 

2007 Mar;20(3):248-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saghafi H, Mahmoodi MJ, Fakhrzadeh H, et al. 

Cardiovascular risk factors in first-degree relatives of 

patients with premature coronary artery disease. Acta 

Cardiol 2006 Dec;61(6):607-13. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-58
and outcome criteria were met for the review questions in 

aggregate 

Sahakyan A, Armenian HK, Breitscheidel L, et al. Feeding 

practices of babies and the development of atopic 

dermatitis in children after 12 months of age in Armenia: Is 

there a signal? Eur J Epidemiol 2006;21(9):723-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saito T, Nanri S, Saito I, et al. A novel approach to 

assessing family history in the prevention of coronary heart 

disease. J Epidemiol 1997 Jun;7(2):85-92. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saito T, Saito I, Nanri S, et al. A quantitative evaluation of 

the effects of sex and age on the positivity of family history 

of hypertension. J Epidemiol 1998 Jun;8(2):99-105. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saito T, Furukawa T, Nanri S, et al. Potential errors 

resulting from sex and age difference in assessing family 

history of diabetes. Prev Med 1999 Jan;28(1):33-9. 

Excluded because no eligible outcomes presented 

Saito T, Nanri S, Saito I, et al. Importance of sex and age 

factor in assessing family history of stroke. J Epidemiol 

2000 Sep;10(5):328-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saito T, Furukawa T, Nanri S, et al. Potential errors 

resulting from sex and age difference in assessing family 

history of coronary heart disease. J Epidemiol 2004 

Mar;14(2):51-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Salem MB, Al Sadoon IO, Hassan MK. Prevalence of 

wheeze among preschool children in Basra governonate, 

southern Iraq. East Mediterr Health J 2002 Jul;8(4-5):503-

8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Salinas CA, Koopmeiners JS, Kwon EM, et al. Clinical 

utility of five genetic variants for predicting prostate cancer 

risk and mortality. Prostate 2009 Mar 1;69(4):363-72. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Salminen M, Vahlberg T, Kivela SL. Effects of familyoriented risk-based prevention on serum cholesterol and 

blood pressure values of children and adolescents. Scand J 

Prim Health Care 2005 Mar;23(1):34-41. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sanders T, Campbell R, Sharp D, et al. Risk constructions 

among people who have a first-degree relative with cancer. 

Health Risk Soc 2003 Mar;5(1):53-69. 

Excluded because not an eligible study design 

Sandhu MS, Luben R, Khaw KT. Self reported non-insulin 

dependent diabetes, family history, and risk of prevalent 

colorectal cancer: population based, cross sectional study. J 

Epidemiol Community Health 2001 Nov;55(11):804-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Santos-Ayarzagoitia M, Salinas-Martinez AM, VillarrealPerez JZ. Gestational diabetes: Validity of ADA and WHO 

diagnostic criteria using NDDG as the reference test. 

Diabetes Res Clin Pract 2006;74(3):322-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saraclar Y, Sekerel BE, Kalayci O, et al. Prevalence of 

asthma symptoms in school children in Ankara, Turkey. 

Respir Med 1998;92(2):203-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Saraiya M, Coughlin SS, Burke W, et al. The role of family 

history in personal prevention practices among US women 

physicians. Community Genet 2001;4(2):102-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Satia JA, McRitchie S, Kupper LL, et al. Genetic testing for 

colon cancer among African-Americans in North Carolina. 

Prev Med 2006 Jan;42(1):51-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-59
Sausenthaler S, Kompauer I, Borte M, et al. Margarine and 

butter consumption, eczema and allergic sensitization in 

children. The LISA birth cohort study. Pediatr Allergy 

Immunol 2006;17(2):85-93. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sautter FJ, Cornwell J, Johnson JJ, et al. Family history 

study of posttraumatic stress disorder with secondary 

psychotic symptoms. Am J Psychiatry 2002 

Oct;159(10):1775-7. 

Excluded because no eligible outcomes presented 

Schambeck CM, Schwender S, Haubitz I, et al. Selective 

screening for the Factor V Leiden mutation: Is it advisable 

prior to the prescription of oral contraceptives? Thromb 

Haemost 1997;78(6):1480-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schattner A, Kasher I, Berrebi A. Causes and outcome of 

deep-vein thrombosis in otherwise-healthy patients under 

50 years. QJM 1997;90(4):283-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Scheuner MT, Wang SJ, Raffel LJ, et al. Family history: a 

comprehensive genetic risk assessment method for the 

chronic conditions of adulthood. Am J Med Genet 1997 

Aug 22;71(3):315-24. 

Excluded because no eligible outcomes presented 

Scheuner MT, Setodji CM, Pankow JS, et al. Relation of 

familial patterns of coronary heart disease, stroke, and 

diabetes to subclinical atherosclerosis: the multi-ethnic 

study of atherosclerosis. Genet Med 2008 Dec;10(12):879-

87. 

Excluded because no eligible outcomes presented 

Schmidt MI, Duncan BB, Bang H, et al. Identifying 

individuals at high risk for diabetes: The Atherosclerosis 

Risk in Communities study. Diabetes Care 

2005;28(8):2013-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Scholte op Reimer WJM, Moons P, De Geest S, et al. 

Cardiovascular risk estimation by professionally active 

cardiovascular nurses: Results from the Basel 2005 Nurses 

Cohort. Eur J Cardiovasc Nurs 2006;5(4):258-63. 

Excluded because no eligible outcomes presented 

Schranz AG, Savona-Ventura C. Long-term significance of 

gestational carbohydrate intolerance: A longitudinal study. 

Exp Clin Endocrinol Diabetes 2002;110(5):219-22. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schroy PC, III, Barrison AF, Ling BS, et al. Family history 

and colorectal cancer screening: a survey of physician 

knowledge and practice patterns. Am J Gastroenterol 2002 

Apr;97(4):1031-6. 

Excluded because family history not collected 

Schulz UG, Flossmann E, Rothwell PM. Heritability of 

ischemic stroke in relation to age, vascular risk factors, and 

subtypes of incident stroke in population-based studies. 

Stroke 2004 Apr;35(4):819-24. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schumacher MC, Slattery ML, Lanier AP, et al. Prevalence 

and predictors of cancer screening among American Indian 

and Alaska native people: The EARTH study. Cancer 

Causes Control 2008;19(7):725-37. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schuurman AG, Zeegers MP, Goldbohm RA, et al. A casecohort study on prostate cancer risk in relation to family 

history of prostate cancer. Epidemiology 1999 

Mar;10(2):192-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schwartz AG, Yang P, Swanson GM. Familial risk of lung 

cancer among nonsmokers and their relatives. Am J 

Epidemiol 1996 Sep 15;144(6):554-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schwartz AG, Rothrock M, Yang P, et al. Increased cancer 

risk among relatives of nonsmoking lung cancer cases. 

Genet Epidemiol 1999;17(1):1-15. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schwartz AG, Siegfried JM, Weiss L. Familial aggregation 

of breast cancer with early onset lung cancer. Genet 

Epidemiol 1999 Nov;17(4):274-84. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-60
and outcome criteria were met for the review questions in 

aggregate 

Schwartz MD, Rimer BK, Daly M, et al. A randomized 

trial of breast cancer risk counseling: The impact on selfreported mammography use. Am J Public Health 1999 

Jun;89(6):924-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Schwartz MD, Valdimarsdottir HB, DeMarco TA, et al. 

Randomized trial of a decision aid for BRCA1/BRCA2 

mutation carriers: Impact on measures of decision making 

and satisfaction. Health Psychol 2009 Jan;28(1):11-9. 

Excluded because not an eligible population 

Sekine I, Abe N, Tsugane S, et al. Does smoking or family 

history influence the prognosis of patients with non-small 

cell lung cancer? Oncol Rep 1997;4(6):1221-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sellers TA, Bazyk AE, Bostick RM, et al. Diet and risk of 

colon cancer in a large prospective study of older women: 

an analysis stratified on family history (Iowa, United 

States). Cancer Causes Control 1998 Aug;9(4):357-67. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sellers TA, Walsh AJ, Grabrick DM, et al. Family history, 

ethnicity, and relative risk of breast cancer in a prospective 

cohort study of older women. Cancer Epidemiol 

Biomarkers Prev 1999 May;8(5):421-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sellers TA, Davis J, Cerhan JR, et al. Interaction of 

waist/hip ratio and family history on the risk of hormone 

receptor-defined breast cancer in a prospective study of 

postmenopausal women. Am J Epidemiol 2002 Feb 

1;155(3):225-33. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sellers TA, Grabrick DM, Vierkant RA, et al. Does folate 

intake decrease risk of postmenopausal breast cancer 

among women with a family history? Cancer Causes 

Control 2004 Mar;15(2):113-20. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Seow A, Quah SR, Nyam D, et al. Food groups and the risk 

of colorectal carcinoma in an Asian population. Cancer 

2002;95(11):2390-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Shah M, Zhu K, Palmer RC, et al. Breast, colorectal, and 

skin cancer screening practices and family history of cancer 

in U.S. women. J Womens Health (Larchmt) 2007 

May;16(4):526-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Shah M, Zhu K, Palmer RC, et al. Family history of cancer 

and utilization of prostate, colorectal and skin cancer 

screening tests in U.S. men. Prev Med 2007 

May;44(5):459-64. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Shah S, Torner J, Mehta A. Prevalence of amblyogenic risk 

factors in siblings of patients with accommodative 

esotropia. J AAPOS 2008 Oct;12(5):487-9. 

Excluded because no eligible outcomes presented 

Shaham J, Gurvich R, Goral A, et al. The risk of breast 

cancer in relation to health habits and occupational 

exposures. Am J Ind Med 2006;49(12):1021-30. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sheinfeld GS, Albert SM. The meaning of risk to first 

degree relatives of women with breast cancer. Women 

Health 2003;37(3):97-117. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sherman JJ, Cordova MJ, Wilson JF, et al. The effects of 

age, gender, and family history on blood pressure of 

normotensive college students. J Behav Med 1996 

Dec;19(6):563-75. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Shirakawa T, Ozono R, Kasagi F, et al. Differential impact 

of family history on age-associated increase in the 

prevalence of hypertension and diabetes in male Japanese 

workers. Hypertens Res 2006 Feb;29(2):81-7. 

D-61
Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Siegmund KD, Province MA, Higgins M, et al. Modeling 

disease incidence rates in families. Epidemiology 1998 

Sep;9(5):557-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sifri RD, Wender R, Paynter N. Cancer risk assessment 

from family history: gaps in primary care practice. J Fam 

Pract 2002 Oct;51(10):856 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Silberberg JS, Wlodarczyk J, Fryer J, et al. Risk associated 

with various definitions of family history of coronary heart 

disease. The Newcastle Family History Study II. Am J 

Epidemiol 1998 Jun 15;147(12):1133-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Silvera SA, Miller AB, Rohan TE. Oral contraceptive use 

and risk of breast cancer among women with a family 

history of breast cancer: a prospective cohort study. Cancer 

Causes Control 2005 Nov;16(9):1059-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Simon MS, Korczak JF, Yee CL, et al. Racial differences in 

the familial aggregation of breast cancer and other female 

cancers. Breast Cancer Res Treat 2005 Feb;89(3):227-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Simon MS, Korczak JF, Yee CL, et al. Breast cancer risk 

estimates for relatives of white and African American 

women with breast cancer in the Women's Contraceptive 

and Reproductive Experiences Study. J Clin Oncol 2006 

Jun 1;24(16):2498-504. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Singh T, Mullick SS, Calton R, et al. Quantification of 

coronary risk score. Indian J Pediatr 2002 Jan;69(1):27-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sipetic S, Vlajinac H, Kocev N, et al. Family history and 

risk of type 1 diabetes mellitus. Acta Diabetol 2002 

Sep;39(3):111-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sipetic SB, Vlajinac HD, Kocev NI, et al. The Belgrade 

childhood diabetes study: A multivariate analysis of risk 

determinants for diabetes. Eur J Public Health 

2005;15(2):117-22. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Siritho S, Thrift AG, McNeil JJ, et al. Risk of ischemic 

stroke among users of the oral contraceptive pill: The 

Melbourne Risk Factor Study (MERFS) Group. Stroke 

2003;34(7):1575-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Skinner HG, Schwartz GG. Serum calcium and incident 

and fatal prostate cancer in the national health and nutrition 

examination survey. Cancer Epidemiol Biomarkers Prev 

2008;17(9):2302-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Slanger T, Mutschelknauss E, Kropp S, et al. Test-retest 

reliability of self-reported reproductive and lifestyle data in 

the context of a German case-control study on breast cancer 

and postmenopausal hormone therapy. Ann Epidemiol 

2007 Dec;17(12):993-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Slattery ML, Mineau GP, Kerber RA. Reproductive factors 

and colon cancer: the influences of age, tumor site, and 

family history on risk (Utah, United States). Cancer Causes 

Control 1995 Jul;6(4):332-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Slattery ML, Potter JD, Duncan DM, et al. Dietary fats and 

colon cancer: assessment of risk associated with specific 

fatty acids. Int J Cancer 1997 Nov 27;73(5):670-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-62
and outcome criteria were met for the review questions in 

aggregate 

Slattery ML, Potter JD, Ma KN, et al. Western diet, family 

history of colorectal cancer, NAT2, GSTM-1 and risk of 

colon cancer. Cancer Causes Control 2000 Jan;11(1):1-8. 

Excluded because not an eligible population 

Slattery ML, Levin TR, Ma K, et al. Family history and 

colorectal cancer: predictors of risk. Cancer Causes Control 

2003 Nov;14(9):879-87. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Slattery ML, Kinney AY, Levin TR. Factors associated 

with colorectal cancer screening in a population-based 

study: The impact of gender, health care source, and time. 

Prev Med 2004;38(3):276-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Slattery ML, Sweeney C, Murtaugh M, et al. Associations 

between apoE genotype and colon and rectal cancer. 

Carcinogenesis 2005;26(8):1422-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Smith AW, Dougall AL, Posluszny DM, et al. 

Psychological distress and quality of life associated with 

genetic testing for breast cancer risk. Psychooncology 

2008;17(8):767-73. 

Excluded because family history not collected 

Smyth DJ, Plagnol V, Walker NM, et al. Shared and 

distinct genetic variants in type 1 diabetes and celiac 

disease. N Engl J Med 2008 Dec 25;359(26):2767-77. 

Excluded because family history not collected 

Soliman AS, Bondy ML, Levin B, et al. Familial 

aggregation of colorectal cancer in Egypt. Int J Cancer 

1998 Sep 11;77(6):811-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Solomon CG, Willett WC, Carey VJ, et al. A prospective 

study of pregravid determinants of gestational diabetes 

mellitus. JAMA 1997;278(13):1078-83. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Somnath CP, Janardhan Reddy YC, Jain S. Is there a 

familial overlap between schizophrenia and bipolar 

disorder? J Affect Disord 2002;72(3):243-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Spencer BA, Babey SH, Etzioni DA, et al. A populationbased survey of prostate-specific antigen testing among 

California men at higher risk for prostate carcinoma. 

Cancer 2006 Feb 15;106(4):765-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Spencer L. Results of a heart disease risk-factor screening 

among traditional college students. J Am Coll Health 2002 

May;50(6):291-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

St Sauver JL, Hagen PT, Cha SS, et al. Agreement between 

patient reports of cardiovascular disease and patient 

medical records. Mayo Clin Proc 2005 Feb;80(2):203-10. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stabile A, Sopo SM, Guerrini B, et al. In vitro production 

of interleukin-4 and interferon-gamma after PHA and PMA 

stimulation, and mononuclear cell proliferative response to 

betalactoglobulin and ovalbumin in neonates with different 

family history of atopy. A follow-up of five years. Pediatr 

Asthma Allergy Immunol 1998;12(4):259-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Staples MP, Giles GG, English DR, et al. Risk of prostate 

cancer associated with a family history in an era of rapid 

increase in prostate cancer diagnosis (Australia). Cancer 

Causes Control 2003 Mar;14(2):161-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stark JR, Bertone-Johnson ER, Costanza ME, et al. Factors 

associated with colorectal cancer risk perception: the role 

of polyps and family history. Health Educ Res 2006 

Oct;21(5):740-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-63
Steck AK, Barriga KJ, Emery LM, et al. Secondary attack 

rate of type 1 diabetes in Colorado families. Diabetes Care 

2005 Feb;28(2):296-300. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stefansson T, Moller PH, Sigurdsson F, et al. Familial risk 

of colon and rectal cancer in Iceland: evidence for different 

etiologic factors? Int J Cancer 2006 Jul 15;119(2):304-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Steinberg KK, Pernarelli JM, Marcus M, et al. Increased 

risk for familial ovarian cancer among Jewish women: a 

population-based case-control study. Genet Epidemiol 

1998;15(1):51-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stencel-Gabriel K, Obuchowicz A, Paul M, et al. Serum 

IgE levels during first 18 months of life in newborns from 

Upper Silesia. Int Rev Allergol Clin Immunol 

2006;12(2):56-60. 

Excluded because no eligible outcomes presented 

Stensland-Bugge E, Bonaa KH, Joakimsen O. Age and sex 

differences in the relationship between inherited and 

lifestyle risk factors and subclinical carotid atherosclerosis: 

the Tromso study. Atherosclerosis 2001 Feb 1;154(2):437-

48. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stephens JH, Moore JW. Can targeted intervention in CRC 

patients' relatives influence screening behaviour? A pilot 

study. Colorectal Dis 2008 Feb;10(2):179-86. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stick SM, Burton PR, Gurrin L, et al. Effects of maternal 

smoking during pregnancy and a family history of asthma 

on respiratory function in newborn infants. Lancet 1996 

Oct 19;348(9034):1060-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stone SN, Hoffman RM, Tollestrup K, et al. Family 

history, Hispanic ethnicity, and prostate cancer risk. Ethn 

Dis 2003;13(2):233-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Stoney CM, Hughes JW. Lipid reactivity among men with 

a parental history of myocardial infarction. 

Psychophysiology 1999 Jul;36(4):484-90. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Strauss ME, Ogrocki PK. Confirmation of an association 

between family history of affective disorder and the 

depressive syndrome in Alzheimer's disease. Am J 

Psychiatry 1996 Oct;153(10):1340-2. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Strom SS, Yamamura Y, Flores-Sandoval FN, et al. 

Prostate cancer in Mexican-Americans: Identification of 

risk factors. Prostate 2008;68(5):563-70. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Strum WB. Impact of a family history of colorectal cancer 

on age at diagnosis, anatomic location, and clinical 

characteristics of colorectal cancer. Int J Gastrointest 

Cancer 2005;35(2):121-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Strum WB. Impact of a family history of colorectal cancer 

on the prevalence of advanced adenomas of the 

rectosigmoid colon at flexible sigmoidoscopy in 3147 

asymptomatic patients. Dig Dis Sci 2006;51(11):2048-52. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sugano K, Nakamura S, Ando J, et al. Cross-sectional 

analysis of germline BRCA1 and BRCA2 mutations in 

Japanese patients suspected to have hereditary 

breast/ovarian cancer. Cancer Sci 2008 Oct;99(10):1967-

76. 

Excluded because not an eligible population 

Sullivan PF, Wells JE, Joyce PR, et al. Family history of 

depression in clinic and community samples. J Affect 

Disord 1996 Oct;40(3):159-68. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-64
Summerton N, Garrood PV. The family history in family 

practice: a questionnaire study. Fam Pract 1997 

Aug;14(4):285-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sundell J, Laine H, Raitakari OT, et al. Positive family 

history of coronary artery disease is associated with 

reduced myocardial vasoreactivity in healthy men. Int J 

Cardiol 2006 Oct 10;112(3):289-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sunsaneevithayakul P, Sutanthavibul A, Kanokpongsakdi 

S, et al. Risk factor-based selective screening program for 

gestational diabetes mellitus in Siriraj Hospital: Result 

from clinical practice guideline. J Med Assoc Thai 

2003;86(8):708-14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sutherland HJ, Lacroix J, Knight J, et al. The Cooperative 

Familial Registry for Breast Cancer Studies: design and 

first year recruitment rates in Ontario. J Clin Epidemiol 

2001 Jan;54(1):93-8. 

Excluded because no eligible outcomes presented 

Suzuki T, Matsuo K, Wakai K, et al. Effect of familial 

history and smoking on common cancer risks in Japan. 

Cancer 2007;109(10):2116-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Svanes C, Jarvis D, Chinn S, et al. Childhood environment 

and adult atopy: results from the European Community 

Respiratory Health Survey. J Allergy Clin Immunol 1999 

Mar;103(3:Pt 1):415-20 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sveger T, Flodmark C-E, Nordborg K, et al. Hereditary 

dyslipidaemias and combined risk factors in children with a 

family history of premature coronary artery disease. Arch 

Dis Child 2000;82(4):292-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Svensson J, Carstensen B, Mortensen HB, et al. Early 

childhood risk factors associated with type 1 diabetes - Is 

gender important? Eur J Epidemiol 2005;20(5):429-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sweeney C, Blair CK, Anderson KE, et al. Risk factors for 

breast cancer in elderly women. Am J Epidemiol 2004 Nov 

1;160(9):868-75. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Sweet KM, Bradley TL, Westman JA. Identification and 

referral of families at high risk for cancer susceptibility. J 

Clin Oncol 2002 Jan 15;20(2):528-37. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Swerdlow AJ, De Stavola BL, Floderus B, et al. Risk 

factors for breast cancer at young ages in twins: an 

international population-based study. J Natl Cancer Inst 

2002 Aug 21;94(16):1238-46. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Szczech R, Bieniaszewski L, Narkiewicz K, et al. Family 

history of hypertension: A novel and potent risk factor for 

premature coronary artery disease. Kardiol Pol 

2002;56(1):68-71. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Szelei-Stevens KA, Kuske RR, Yantsos VA, et al. The 

influence of young age and positive family history of breast 

cancer on the prognosis of ductal carcinoma in situ treated 

by excision with or without radiation therapy or by 

mastectomy. Int J Radiat Oncol Biol Phys 2000 Nov 

1;48(4):943-9. 

Excluded because no eligible outcomes presented 

Taira K, Bujo H, Kobayashi J, et al. Positive family history 

for coronary heart disease and 'midband lipoproteins' are 

potential risk factors of carotid atherosclerosis in familial 

hypercholesterolemia. Atherosclerosis 2002 

Feb;160(2):391-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tam WH, Yang XL, Chan JCN, et al. Progression to 

impaired glucose regulation, diabetes and metabolic 

D-65
syndrome in Chinese women with a past history of 

gestational diabetes. Diabetes Metab Res Rev 

2007;23(6):485-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tammemagi CM, Freedman MT, Church TR, et al. Factors 

associated with human small aggressive non-small cell lung 

cancer. Cancer Epidemiol Biomarkers Prev 

2007;16(10):2082-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tanaka K, Miyake Y, Sasaki S, et al. Maternal smoking 

and environmental tobacco smoke exposure and the risk of 

allergic diseases in Japanese infants: The Osaka maternal 

and child health study. J Asthma 2008;45(9):833-8. 

Excluded because no eligible outcomes presented 

Taraboanta C, Wu E, Lear S, et al. Subclinical 

atherosclerosis in subjects with family history of premature 

coronary artery disease. Am Heart J 2008 Jun;155(6):1020-

6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tavani A, Braga C, La Vecchia C, et al. Attributable risks 

for breast cancer in Italy: education, family history and 

reproductive and hormonal factors. Int J Cancer 1997 Jan 

17;70(2):159-63. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tavani A, Ricci E, La Vecchia C, et al. Influence of 

menstrual and reproductive factors on ovarian cancer risk 

in women with and without family history of breast or 

ovarian cancer. Int J Epidemiol 2000 Oct;29(5):799-802. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tavani A, Bosetti C, Dal Maso L, et al. Influence of 

selected hormonal and lifestyle factors on familial 

propensity to ovarian cancer. Gynecol Oncol 2004 

Mar;92(3):922-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tavani A, Bertuzzi M, Gallus S, et al. Risk factors for nonfatal acute myocardial infarction in Italian women. Prev 

Med 2004;39(1):128-34. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tavani A, Augustin L, Bosetti C, et al. Influence of 

selected lifestyle factors on risk of acute myocardial 

infarction in subjects with familial predisposition for the 

disease. Prev Med 2004 Apr;38(4):468-72. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Taylor AJ, Bindeman J, Bhattarai S, et al. Subclinical 

calcified atherosclerosis in men and its association with a 

family history of premature coronary heart disease in firstand second-degree relatives. Prev Cardiol 2004;7(4):163-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Taylor R, Boyages J. Absolute risk of breast cancer for 

Australian women with a family history. Aust N Z J Surg 

2000 Oct;70(10):725-31. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Terdiman JP, Levin TR, Allen BA, et al. Hereditary 

nonpolyposis colorectal cancer in young colorectal cancer 

patients: High-risk clinic versus population-based registry. 

Gastroenterology 2002;122(4):940-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Thalib L, Wedren S, Granath F, et al. Breast cancer 

prognosis in relation to family history of breast and ovarian 

cancer. Br J Cancer 2004 Apr 5;90(7):1378-81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Thompson IM, Ankerst DP, Chi C, et al. Prediction of 

prostate cancer for patients receiving finasteride: Results 

from the prostate cancer prevention trial. J Clin Oncol 

2007;25(21):3076-81. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Thomsen SF, Ulrik CS, Kyvik KO, et al. Importance of 

genetic factors in the etiology of atopic dermatitis: a twin 

study. Allergy Asthma Proc 2007 Sep;28(5):535-9. 

Excluded because family history not collected 

D-66
Thorand B, Liese AD, Metzger MH, et al. Can inaccuracy 

of reported parental history of diabetes explain the maternal 

transmission hypothesis for diabetes? Int J Epidemiol 2001 

Oct;30(5):1084-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tiller K, Meiser B, Gould L, et al. Knowledge of risk 

management strategies, and information and risk 

management preferences of women at increased risk for 

ovarian cancer. Psychooncology 2005 Apr;14(4):249-61. 

Excluded because not an eligible population 

Timko C, Cronkite RC, Berg EA, et al. Children of parents 

with unipolar depression: A comparison of stably remitted, 

partially remitted, and nonremitted parents and 

nondepressed controls. Child Psychiatry Hum Dev 

2002;32(3):165-85. 

Excluded because family history not collected 

Timonen M, Jokelainen J, Herva A, et al. Presence of atopy 

in first-degree relatives as a predictor of a female proband's 

depression: Results from the Northern Finland 1966 Birth 

Cohort. J Allergy Clin Immunol 2003;111(6):1249-54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tomac N, Demirel F, Acun C, et al. Prevalence and risk 

factors for childhood asthma in Zonguldak, Turkey. 

Allergy Asthma Proc 2005 Sep;26(5):397-402. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tonstad S, Refsum H, Sivertsen M, et al. Relation of total 

homocysteine and lipid levels in children to premature 

cardiovascular death in male relatives. Pediatr Res 1996 

Jul;40(1):47-52. 

Excluded because no eligible outcomes presented 

Toren K, Hermansson B-A. Incidence rate of adult-onset 

asthma in relation to age, sex, atopy and smoking: A 

Swedish population-based study of 15 813 adults. Int J 

Tuberc Lung Dis 1999;3(3):192-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tozzi F, Prokopenko I, Perry JD, et al. Family history of 

depression is associated with younger age of onset in 

patients with recurrent depression. Psychol Med 

2008;38(5):641-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tracy KA, Quillin JM, Wilson DB, et al. The impact of 

family history of breast cancer and cancer death on 

women's mammography practices and beliefs. Genet Med 

2008 Aug;10(8):621-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tremeau F, Staner L, Duval F, et al. Suicide attempts and 

family history of suicide in three psychiatric populations. 

Suicide Life Threat Behav 2005;35(6):702-13. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Trentham-Dietz A, Newcomb PA, Nichols HB, et al. Breast 

cancer risk factors and second primary malignancies among 

women with breast cancer. Breast Cancer Res Treat 2007 

Oct;105(2):195-207. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tripathy D, Lindholm E, Isomaa B, et al. Familiality of 

metabolic abnormalities is dependent on age at onset and 

phenotype of the type 2 diabetic proband. Am J Physiol 

Endocrinol Metab 2003 Dec;285(6):E1297-E1303 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tsolaki M, Fountoulakis K, Chantzi E, et al. Risk factors 

for clinically diagnosed Alzheimer's disease: A casecontrol study of a Greek population. Int Psychogeriatr 

1997;9(3):327-41. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tung KH, Goodman MT, Wu AH, et al. Aggregation of 

ovarian cancer with breast, ovarian, colorectal, and prostate 

cancer in first-degree relatives. Am J Epidemiol 2004 Apr 

15;159(8):750-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ture M, Kurt I, Kurum T. Analysis of intervariable 

relationships between major risk factors in the development 

of coronary artery disease: A classification tree approach. 

Anadolu Kardiyoloji Dergisi 2007;7(2):140-5. 

Excluded because no eligible outcomes presented 

D-67
Tyagi A, Morris J. Using decision analytic methods to 

assess the utility of family history tools. Am J Prev Med 

2003 Feb;24(2):199-207. 

Excluded because not an eligible population 

Tyndel S, Clements A, Bankhead C, et al. Mammographic 

screening for young women with a family history of breast 

cancer: Knowledge and views of those at risk. Br J Cancer 

2008;99(7):1007-12. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tytherleigh MG, Ng VV, Mathew LO, et al. Colonoscopy 

for screening and follow up of patients with a family 

history of colorectal cancer. Colorectal Dis 2008 

Jun;10(5):506-11. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Tytherleigh MG, Ng VV, Mathew LO, et al. Colonoscopy 

for screening and follow up of patients with a family 

history of colorectal cancer. Colorectal Dis 

2008;10(5):506-11. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Uchigata Y, Otani T, Takaike H, et al. Time-course 

changes in clinical features of early-onset Japanese type 1 

and type 2 diabetes: TWMU hospital-based study. Diabetes 

Res Clin Pract 2008 Oct;82(1):80-6. 

Excluded because no eligible outcomes presented 

Ueda K, Tsukuma H, Tanaka H, et al. Estimation of 

individualized probabilities of developing breast cancer for 

Japanese women. Breast Cancer 2003;10(1):54-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Urashima M, Wada T, Fukumoto T, et al. Prevalence of 

metabolic syndrome in a 22,892 Japanese population and 

its association with life style. JMAJ 2005;48(9):441-50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Uzzo RG, Brown JG, Horwitz EM, et al. Prevalence and 

patterns of self-initiated nutritional supplementation in men 

at high risk of prostate cancer. BJU Int 2004 

May;93(7):955-60. 

Excluded because family history not collected 

Valdez R, Yoon PW, Liu T, et al. Family history and 

prevalence of diabetes in the U.S. population: the 6-year 

results from the National Health and Nutrition Examination 

Survey (1999-2004). Diabetes Care 2007 Oct;30(10):2517-

22. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Valentine RJ, Verstraete R, Clagett GP, et al. Premature 

cardiovascular disease is common in relatives of patients 

with premature peripheral atherosclerosis. Arch Intern Med 

2000 May 8;160(9):1343-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

van der Net JB, Janssens AC, Defesche JC, et al. 

Usefulness of genetic polymorphisms and conventional risk 

factors to predict coronary heart disease in patients with 

familial hypercholesterolemia. Am J Cardiol 2009 Feb 

1;103(3):375-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Van Der Sande MA, Walraven GE, Milligan PJ, et al. 

Family history: an opportunity for early interventions and 

improved control of hypertension, obesity and diabetes. 

Bull World Health Organ 2001;79(4):321-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

van Dijk DA, Oostindier MJ, Kloosterman-Boele WM, et 

al. Family history is neglected in the work-up of patients 

with colorectal cancer: a quality assessment using cancer 

registry data. Fam Cancer 2007;6(1):131-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

van Dooren S, Seynaeve C, Rijnsburger AJ, et al. The 

impact of having relatives affected with breast cancer on 

psychological distress in women at increased risk for 

hereditary breast cancer. Breast Cancer Res Treat 2005 

Jan;89(1):75-80. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

van Ojen R, Hooijer C, Bezemer D, et al. Late-life 

depressive disorder in the community: II. The relationship 

between psychiatric history, MMSE and family history. Br 

J Psychiatry 1995 Mar;166(3):316-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-68
and outcome criteria were met for the review questions in 

aggregate 

Van dA, I, Van Golde RJ, Tuerlings JH, et al. 

Underestimation of subfertility among relatives when using 

a family history: taboo bias. J Androl 2003 Mar;24(2):285-

8. 

Excluded because no eligible outcomes presented 

Vasen HFA, Taal BG, Nagengast FM, et al. Hereditary 

nonpolyposis colorectal cancer: Results of long-term 

surveillance in 50 families. Eur J Cancer 1995;31(7-

8):1145-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Verkooijen HM, Fioretta G, Chappuis PO, et al. Set-up of a 

population-based familial breast cancer registry in Geneva, 

Switzerland: validation of first results. Ann Oncol 2004 

Feb;15(2):350-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Verkooijen HM, Fioretta G, Rapiti E, et al. Family history 

of breast or ovarian cancer modifies the risk of secondary 

leukemia after breast cancer: results from a populationbased study. Int J Cancer 2008 Mar 1;122(5):1114-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Vestbo E, Damsgaard EM, Froland A, et al. Clinical 

features in persons with a family history of diabetes 

compared to controls (The Second Generation Fredericia 

Study). J Intern Med 1996 Dec;240(6):381-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Viana DV, Goes JR, Coy CS, et al. Family history of 

cancer in Brazil: is it being used? Fam Cancer 

2008;7(3):229-32. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Vicencio JCA, Gonzalez-Andaya AM. Sensitization to food 

and aeroallergens in children with atopic dermatitis seen at 

the University of Santo Tomas Hospital Allergy Clinic. 

Santo Tomas Journal of Medicine 2005;52(3):92-100. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Vikram NK, Tandon N, Misra A, et al. Correlates of Type 

2 diabetes mellitus in children, adolescents and young 

adults in north India: a multisite collaborative case-control 

study. Diabet Med 2006 Mar;23(3):293-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Viladiu P, Izquierdo A, de Sanjose S, et al. A breast cancer 

case-control study in Girona, Spain. Endocrine, familial 

and lifestyle factors. Eur J Cancer Prev 1996;5(5):329-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Villani AC, Lemire M, Fortin G, et al. Common variants in 

the NLRP3 region contribute to Crohn's disease 

susceptibility. Nat Genet 2009 Jan;41(1):71-6. 

Excluded because not an eligible population 

Villarreal AB, Sanin Aguirre LH, Tellez Rojo MM, et al. 

Risk factors for asthma in school children from Ciudad 

Juarez, Chihuahua. J Asthma 2003;40(4):413-23. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Vitullo F, Marchioli R, Di Mascio R, et al. Family history 

and socioeconomic factors as predictors of myocardial 

infarction, unstable angina and stroke in an Italian 

population. PROGETTO 3A Investigators. Eur J Epidemiol 

1996 Apr;12(2):177-85. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

von Eyben FE, Mouritsen E, Holm J, et al. Smoking, low 

density lipoprotein cholesterol, fibrinogen and myocardial 

infarction before 41 years of age: A Danish case-control 

study. J Cardiovasc Risk 2002;9(3):171-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wadonda-Kabondo N, Sterne JA, Golding J, et al. 

Association of parental eczema, hayfever, and asthma with 

atopic dermatitis in infancy: birth cohort study. Arch Dis 

Child 2004 Oct;89(10):917-21. 

Excluded because no eligible outcomes presented 

Wakefield CE, Meiser B, Homewood J, et al. Randomized 

trial of a decision aid for individuals considering genetic 

testing for hereditary nonpolyposis colorectal cancer risk. 

Cancer 2008 Sep;113(5):956-65. 

Excluded because no eligible outcomes presented 

D-69
Wakefield CE, Meiser B, Homewood J, et al. A 

randomized controlled trial of a decision aid for women 

considering genetic testing for breast and ovarian cancer 

risk. Breast Cancer Res Treat 2008 Jan;107(2):289-301. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wakefield CE, Meiser B, Homewood J, et al. A 

randomized trial of a breast/ovarian cancer genetic testing 

decision aid used as a communication aid during genetic 

counseling. Psychooncology 2008 Aug;17(8):844-54. 

Excluded because family history not collected 

Waldhoer T, Haidinger G, Feenstra O, et al. The influence 

of genetic predisposition on the prevalence of atopic 

diseases in Carinthian school children. Acta Med Austriaca 

2000;27(5):141-4. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Waldhor T, Schober E, Rami B, et al. The prevalence of 

IDDM in the first degree relatives of children newly 

diagnosed with IDDM in Austria - A population-based 

study. Exp Clin Endocrinol Diabetes 1999;107(5):323-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Walker GR, Schlesselman JJ, Ness RB. Family history of 

cancer, oral contraceptive use, and ovarian cancer risk. Am 

J Obstet Gynecol 2002 Jan;186(1):8-14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wallace E, Hinds A, Campbell H, et al. A cross-sectional 

survey to estimate the prevalence of family history of 

colorectal, breast and ovarian cancer in a Scottish general 

practice population. Br J Cancer 2004 Oct 18;91(8):1575-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Walsh PC, Partin AW. Family history facilitates the early 

diagnosis of prostate carcinoma. Cancer 1997 Nov 

1;80(9):1871-4. 

Excluded because not an eligible study design 

Walter FM, Emery J. 'Coming down the line'-- patients' 

understanding of their family history of common chronic 

disease. Ann Fam Med 2005 Sep;3(5):405-14. 

Excluded because not an eligible study design 

Walter FM, Emery J. Perceptions of family history across 

common diseases: a qualitative study in primary care. Fam 

Pract 2006 Aug;23(4):472-80. 

Excluded because not an eligible study design 

Wang I-J, Guo YL, Hwang K-C, et al. Genetic and 

environmental predictors for pediatric atopic dermatitis. 

Acta Paediatrica Taiwanica 2006;47(5):238-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wang NY, Young JH, Meoni LA, et al. Blood pressure 

change and risk of hypertension associated with parental 

hypertension: the Johns Hopkins Precursors Study. Arch 

Intern Med 2008 Mar 24;168(6):643-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wang TN, Chao YY, Wang TH, et al. Familial risk of 

asthma among adolescents and their relatives in Taiwan. J 

Asthma 2001 Sep;38(6):485-94. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Warner E, Goel V, Ondrusek N, et al. Pilot study of an 

information aid for women with a family history of breast 

cancer. Health Expect 1999;2(2):118-28. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wattacheril J, Kramer JR, Richardson P, et al. Lagtimes in 

diagnosis and treatment of colorectal cancer: Determinants 

and association with cancer stage and survival. Aliment 

Pharmacol Ther 2008;28(9):1166-74. 

Excluded because no eligible outcomes presented 

Webb PM, Byrne C, Schnitt SJ, et al. Family history of 

breast cancer, age and benign breast disease. Int J Cancer 

2002 Jul 20;100(3):375-8. 

Excluded because no eligible outcomes presented 

Weeks SK, O'Connor PC. The FAMTOOL family health 

assessment tool. Rehabil Nurs 1997 Jul;22(4):188-91. 

Excluded because family history not collected 

Wei JN, Sung FC, Lin CC, et al. National Surveillance for 

Type 2 Diabetes Mellitus in Taiwanese Children. JAMA 

2003;290(10):1345-50. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-70
Weinrich S, Royal C, Pettaway CA, et al. Interest in genetic 

prostate cancer susceptibility testing among african 

American men. Cancer Nurs 2002 Feb;25(1):28-34. 

Excluded because no eligible outcomes presented 

Weinrich SP, Faison-Smith L, Hudson-Priest J, et al. 

Stability of self-reported family history of prostate cancer 

among African American men. J Nurs Meas 2002;10(1):39-

46. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Weires MB, Tausch B, Haug PJ, et al. Familiality of 

diabetes mellitus. Exp Clin Endocrinol Diabetes 2007 

Nov;115(10):634-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Weiss HA, Brinton LA, Brogan D, et al. Epidemiology of 

in situ and invasive breast cancer in women aged under 45. 

Br J Cancer 1996 May;73(10):1298-305. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

West DS, Greene PG, Kratt PP, et al. The impact of a 

family history of breast cancer on screening practices and 

attitudes in low-income, rural, African American women. J 

Womens Health (Larchmt) 2003 Oct;12(8):779-87. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Whitaker JA, Davis KL, Lauer C. Is there a need for 

screening for type 2 diabetes in seventh graders? J Am 

Acad Nurse Pract 2004 Nov;16(11):496-501. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

White DB, Bonham VL, Jenkins J, et al. Too many 

referrals of low-risk women for BRCA1/2 genetic services 

by family physicians. Cancer Epidemiol Biomarkers Prev 

2008 Nov;17(11):2980-6. 

Excluded because family history not collected 

White HL, Roberts DH. Cholesterol management in 

general practice. Curr Med Res Opin 1997;14(1):53-62. 

Excluded because family history not collected 

Whittemore AS, Wu AH, Kolonel LN, et al. Family history 

and prostate cancer risk in black, white, and Asian men in 

the United States and Canada. Am J Epidemiol 1995 Apr 

15;141(8):732-40. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wickens K, Crane J, Kemp T, et al. A case-control study of 

risk factors for asthma in New Zealand children. Aust N Z J 

Public Health 2001;25(1):44-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wickramaratne PJ, Greenwald S, Weissman MM. 

Psychiatric disorders in the relatives of probands with 

prepubertal-onset or adolescent-onset major depression. J 

Am Acad Child Adolesc Psychiatry 2000 

Nov;39(11):1396-405. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wiegman A, Rodenburg J, de Jongh S, et al. Family history 

and cardiovascular risk in familial hypercholesterolemia: 

data in more than 1000 children. Circulation 2003 Mar 

25;107(11):1473-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wilhelmsen L, Lappas G, Rosengren A. Risk of coronary 

events by baseline factors during 28 years follow-up and 

three periods in a random population sample of men. J 

Intern Med 2004;256(4):298-307. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Willemsen G, van Beijsterveldt TC, van Baal CG, et al. 

Heritability of self-reported asthma and allergy: a study in 

adult Dutch twins, siblings and parents. Twin Res Human 

Genet 2008 Apr;11(2):132-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Williams KP, Sheppard VB, Todem D, et al. Family 

matters in mammography screening among AfricanAmerican women age [greater-than or equal to]40. J Natl 

Med Assoc 2008;100(5):508-15. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Williams MA, Qiu C, Dempsey JC, et al. Familial 

Aggregation of Type 2 Diabetes and Chronic Hypertension 

D-71
in Women with Gestational Diabetes Mellitus. J Reprod 

Med 2003;48(12):955-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Williams RR, Hunt SC, Heiss G, et al. Usefulness of 

cardiovascular family history data for population-based 

preventive medicine and medical research (the Health 

Family Tree Study and the NHLBI Family Heart Study). 

Am J Cardiol 2001 Jan 15;87(2):129-35. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Williams T, Clarke V, Borland R. Breast cancer and family 

history: evaluation of a community resource. Health 

Promot J Aust 2000 Dec;10(3):224-9. 

Excluded because no eligible outcomes presented 

Williamson DE, Ryan ND, Birmaher B, et al. A casecontrol family history study of depression in adolescents. J 

Am Acad Child Adolesc Psychiatry 1995 Dec;34(12):1596-

607. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Winawer SJ, Zauber AG, Gerdes H, et al. Risk of colorectal 

cancer in the families of patients with adenomatous polyps. 

N Engl J Med 1996;334(2):82-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wohlfahrt J, Olsen JH, Melbye M. Breast cancer risk after 

childbirth in young women with family history (Denmark). 

Cancer Causes Control 2002;13(2):169-74. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wolf AMD, Nasser JF, Wolf AM, et al. The impact of 

informed consent on patient interest in prostate-specific 

antigen screening. Arch Intern Med 1996;156(12):1333-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wolf AMD, Philbrick JT, Schorling JB. Predictors of 

interest in prostate-specific antigen screening and the 

impact of informed consent: What should we tell our 

patients? Am J Med 1997;103(4):308-14. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wong TY, Mohamed Q, Klein R, et al. Do retinopathy 

signs in non-diabetic individuals predict the subsequent risk 

of diabetes? Br J Ophthalmol 2006;90(3):301-3. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wood ME, Stockdale A, Flynn BS. Interviews with 

primary care physicians regarding taking and interpreting 

the cancer family history. Fam Pract 2008 Oct;25(5):334-

40. 

Excluded because not an eligible study design 

Woodward M, Brindle P, Tunstall-Pedoe H, et al. Adding 

social deprivation and family history to cardiovascular risk 

assessment: the ASSIGN score from the Scottish Heart 

Health Extended Cohort (SHHEC). Heart 2007 

Feb;93(2):172-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wrensch M, Chew T, Farren G, et al. Risk factors for 

breast cancer in a population with high incidence rates. 

Breast Cancer Res 2003;5(4):R88-102. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wright CE, O'Donnell K, Brydon L, et al. Family history of 

cardiovascular disease is associated with cardiovascular 

responses to stress in healthy young men and women. Int J 

Psychophysiol 2007 Mar;63(3):275-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wu AH, Fontham ET, Reynolds P, et al. Family history of 

cancer and risk of lung cancer among lifetime nonsmoking 

women in the United States. Am J Epidemiol 1996 Mar 

15;143(6):535-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Wu PF, Lee CH, Wang MJ, et al. Cancer aggregation and 

complex segregation analysis of families with female nonsmoking lung cancer probands in Taiwan. Eur J Cancer 

2004 Jan;40(2):260-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

D-72
Wyshak G. Behavior, heredity, and diabetes in college 

alumnae. J Wom Health Gend Base Med 2002;11(6):549-

54. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yang P-S, Yang T-L, Liu C-L, et al. A case-control study 

of breast cancer in Taiwan - A low-incidence area. Br J 

Cancer 1997;75(5):752-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yang Q, Khoury MJ, Rodriguez C, et al. Family history 

score as a predictor of breast cancer mortality: prospective 

data from the Cancer Prevention Study II, United States, 

1982-1991. Am J Epidemiol 1998 Apr 1;147(7):652-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yang X-Z, Liu Y, Mi J, et al. Pre-clinical atherosclerosis 

evaluated by carotid artery intima-media thickness and the 

risk factors in children. Chin Med J (Engl) 

2007;120(5):359-62. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yarnell J, Yu S, Patterson C, et al. Family history, 

longevity, and risk of coronary heart disease: the PRIME 

Study. Int J Epidemiol 2003 Feb;32(1):71-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yasui Y, Newcomb PA, Trentham-Dietz A, et al. Familial 

relative risk estimates for use in epidemiologic analyses. 

Am J Epidemiol 2006 Oct 1;164(7):697-705. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yeh CY, Chiang JM, Wang JY, et al. Colonoscopic 

surveillance in asymptomatic persons with family history 

of colorectal cancer. Formos J Surg 1999;32(3):111-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yeung EH, Pankow JS, Astor BC, et al. Increased risk of 

type 2 diabetes from a family history of coronary heart 

disease and type 2 diabetes. Diabetes Care 2007 

Jan;30(1):154-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yip CH, bt Mohd Taib NA, Lau PC. Does a positive family 

history influence the presentation of breast cancer? Asian 

Pac J Cancer Prev 2008 Jan;9(1):63-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yokoe T, Takei H, Horiguchi J, et al. Family history in 

participants of breast cancer screening. Oncol Rep 

1997;4(5):973-6. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yokoyama H, Kawai K, Ohishi M, et al. Familial 

predisposition to cardiovascular risk and disease 

contributes to cardiovascular risk and disease interacting 

with other cardiovascular risk factors in diabetesImplication for common soil (JDDM 14). Atherosclerosis 

2008;201(2):332-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yologlu S, Sezgin AT, Sezgin N, et al. Determination of 

risk factors in obese and non-obese patients with coronary 

artery disease. Acta Cardiol 2005;60(6):625-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yong MC, Zhou XJ, Lee SC. The importance of paternal 

family history in hereditary breast cancer is 

underappreciated by health care professionals. Oncology 

2003;64(3):220-6. 

Excluded because family history not collected 

Yoshinaga M, Nagashima M, Shibata T, et al. Who Is at 

Risk for Cardiac Events in Young Patients with Long QT 

Syndrome? Circ J 2003;67(12):1007-12. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Young CA, Kumar S, Young MJ, et al. Excess maternal 

history of diabetes in Caucasian and Afro-origin noninsulin-dependent diabetic patients suggests dominant 

maternal factors in disease transmission. Diabetes Res Clin 

Pract 1995;28(1):47-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

D-73
and outcome criteria were met for the review questions in 

aggregate 

Youssef AA, Valdez R, Elkasabany A, et al. Time-course 

of adiposity and fasting insulin from childhood to young 

adulthood in offspring of parents with coronary artery 

disease: the Bogalusa Heart Study. Ann Epidemiol 2002 

Nov;12(8):553-9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Yung AR, Phillips LJ, Yuen HP, et al. Risk factors for 

psychosis in an ultra high-risk group: Psychopathology and 

clinical features. Schizophr Res 2004;67(2-3):131-42. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zeegers MP, Schouten LJ, Goldbohm RA, et al. A 

compendium of familial relative risks of cancer among first 

degree relatives: A population-based study. Int J Cancer 

2008;123(7):1664-73. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zhang Y, Shu XO, Gao YT, et al. Family history of cancer 

and risk of lung cancer among nonsmoking Chinese 

women. Cancer Epidemiol Biomarkers Prev 2007 

Nov;16(11):2432-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zheng YF, Saito T, Takahashi M, et al. Factors associated 

with intentions to adhere to colorectal cancer screening 

follow-up exams. BMC Public Health 2006;6:272 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zhou BS, Wang TJ, Guan P, et al. Indoor air pollution and 

pulmonary adenocarcinoma among females: a case-control 

study in Shenyang, China. Oncol Rep 2000 Nov;7(6):1253-

9. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zhou WS, Hu ZP, Deng JG, et al. Comparative analysis of 

the risk factors of ischemic stroke in the middle-aged and 

youth. Chin J Clin Rehabil 2005;9(9):184-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zhu S, Toyoshima H, Kondo T, et al. Short- and long-term 

reliability of information on previous illness and family 

history as compared with that on smoking and drinking 

habits in questionnaire surveys. J Epidemiol 2002 

Mar;12(2):120-5. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zimmerman M, McGlinchey JB, Young D, et al. 

Diagnosing major depressive disorder VII: family history 

as a diagnostic criterion. J Nerv Ment Dis 2006 

Sep;194(9):704-7. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ziogas A, Gildea M, Cohen P, et al. Cancer risk estimates 

for family members of a population-based family registry 

for breast and ovarian cancer. Cancer Epidemiol 

Biomarkers Prev 2000 Jan;9(1):103-11. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Ziv E, Shepherd J, Smith-Bindman R, et al. 

Mammographic breast density and family history of breast 

cancer. J Natl Cancer Inst 2003 Apr 2;95(7):556-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zlot AI, Bland MP, Silvey K, et al. Influence of family 

history of diabetes on health care provider practice and 

patient behavior among nondiabetic Oregonians. Prev 

Chronic Dis 2009 Jan;6(1):A27 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zodpey SP, Tiwari RR, Kulkarni HR. Risk factors for 

haemorrhage stroke: A case-control study. Public Health 

2000;114(3):177-82. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zureik M, Touboul PJ, Bonithon-Kopp C, et al. Differential 

association of common carotid intima-media thickness and 

carotid atherosclerotic plaques with parental history of 

premature death from coronary heart disease : the EVA 

study. Arterioscler Thromb Vasc Biol 1999 Feb;19(2):366-

71. 

D-74
D-75

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 

Zutavern A, Hirsch T, Leupold W, et al. Atopic dermatitis, 

extrinsic atopic dermatitis and the hygiene hypothesis: 

results from a cross-sectional study. Clin Exp Allergy 2005 

Oct;35(10):1301-8. 

Excluded because it does not meet all criteria for any one 

review question, although each of population, intervention 

and outcome criteria were met for the review questions in 

aggregate 
Appendix E - Technical Expert Panel and Peer Reviewers 

Task Order Officer 

Supriya Janakiraman, M.D., M.P.H. 

Staff Service Fellow, Center for Outcomes and Evidence AHRQ 

Rockville, MD USA 

Technical Expert Panel 

In designing the study questions and methodology at the outset of this report, the EPC consulted 

several technical and content experts. Broad expertise and perspectives are sought. Divergent 

and conflicted opinions are common and perceived as health scientific discourse that results in a 

thoughtful, relevant systematic review. Therefore, in the end, study questions, design and/or 

methodologic approaches do not necessarily represent the views of individual technical and 

content experts. 

Al Berg, M.D., M.P.H., Official representative on TEP for partners 

Professor 

Department of Family Medicine 

University of Washington School of Medicine 

Lisa Madlensky, Ph.D. 

Moores UCSD Cancer Center 

University of California 

Louise S. Acheson, M.D., M.S. 

Department of Family Medicine 

Case Western Reserve University 

Wylie Burke, M.D., Ph.D. 

Professor and Chair 

Department of Medical History and Ethics 

University of Washington

E-1
Peer Reviewers 

Peer reviewer comments on a preliminary draft of this report were considered by the EPC in 

preparation of this final report. Synthesis of the scientific literature presented here does not 

necessarily represent the views of individual reviewers. 

Joy Larsen Haidle, M.S., C.G.C. 

Genetic Counselor 

Hubert H. Humphrey Cancer Center 

Robbinsdale, MN 

Ted Adams PhD MPH 

Research professor, Cardiovascular Genetics Division 

University of Utah School of Medicine 

Salt Lake City, UT 

Doug Campos-Outcalt M.D, M.P.A. 

Associate Chair 

University of Arizona College of Medicine 

Department of Family and Community Medicine 

Phoenix, AZ 

Karen Edwards M.D. 

Associate Professor, Epidemiology 

Department of Epidemiology

University of Washington 

Seattle, WA 

Jon Emery M.D. 

Department of General Practice 

University of Western Australia 

Claremont, WA 

Australia 

Kent McKelvey 

Assistant Professor, Family and Preventive Medicine and 

Director of Cancer Genetics Services 

University of Arkansas 

Little Rock, AR 

Kristin Peterson Oehlke MS CGC 

State Genomics Coordinator 

Minnesota Department of Health 

St. Paul, MN 

E-2
E-3

Jon Tilburt M.D 

Division of General Internal Medicine 

The Program in Professionalism and Bioethics 

Mayo Clinic 

Rochester, MN 

Barbara P. Yawn, M.D., M.Sc, FAAFP 

Director of Research 

Department of Research and Education 

Olmsted Medical Center 

Rochester, MN 

Carrie Zabel M.S., C.G.C 

Genetic counselor 

Genomics Education Program 

Mayo Clinic 

Rochester, MN