Evidence Report/Technology Assessment 

Number 179 

Clinical Utility of Cancer Family History Collection 

in Primary Care 

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. 290-02-0020 

Prepared by: 

McMaster University Evidence-based Practice Center, Hamilton, ON 

Task Order Leaders: 

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

Nadeem Qureshi, M.B.B.S., D.M. 

Authors: 

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

Nadeem Qureshi, M.B.B.S., D.M. 

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

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

Homa Keshavarz, M.Sc., Ph.D. 

Parminder Raina, B.Sc., Ph.D. 

AHRQ Publication No. 09-E007 

April 2009
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: 

Wilson B, Qureshi N, Little J, Santaguida P, Carroll J, Allanson J, Keshavarz H, Raina P. 

Clinical Utility of Cancer Family History Collection in Primary Care. Evidence 

Report/Technology Assessment No.179. (Prepared by the McMaster University Evidence-based 

Practice Center, under Contract No. 290-02-0020.) AHRQ Publication No. 09-E007. Rockville, 

MD: Agency for Healthcare Research and Quality. 

April 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. 
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 

Richard E. Besser, M.D. 

Acting Director 

Centers for Disease Control and Prevention Supriya Janakiraman, M.D., M.P.H. 

EPC Program Task Order Officer 

Agency for Healthcare Research and Quality 
Acknowledgments 

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

following people for their contributions. 

We are grateful to Gurvaneet Randhawa, Supriya Janakiraman and members of the technical 

expert panel who were instrumental in developing the questions and defining the scope of this 

review: Robert German, Rodolfo Valdez, Lisa Madlensky, and Louise Acheson. 

We would also like to thank Maureen Rice for developing and running the search strategies; 

Catherine Salmon, Connie Freeborn, Robert Stevens, Lynda Booker, Solina Yoo, Kate Walker, 

Sara Kaffashian, and Maureen Rice for screening the citations; and Sara Shepley for managing 

the references in RefMan and SRS and for assistance in article retrieval. 

Thank you to Rachel Morris for the many hours of screening and data abstraction. 

We would like to thank Valery L’Heureux and Silvia Visentin at the University of Ottawa for 

their administrative assistance to the investigators. 

Finally we would like to say thank you to Mary Gauld, Maureen Rice, Roxanne Cheeseman, 

and Cecile Royer for their invaluable input in the editing and formatting of this report. 
Structured Abstract 

Objectives: This systematic review aimed to evaluate, within unselected populations: the (1) 

performance of family history (FHx)-based models in predicting cancer risk; (2) overall benefits 

and harms associated with established cancer prevention interventions; (3) impact of FHx-based 

risk information on the uptake of preventive interventions; and (4) potential for harms associated 

with collecting cancer FHx. 

Data Sources: MEDLINE®, EMBASE®, CINAHL® Cochrane Central®, Cochrane Database of 

Systematic Reviews, and PsycINFO were searched from 1990 to June 2008 inclusive. Cancer 

guidelines and recommendations were searched from 2002 forward and systematic reviews from 

2003 to June 2008. 

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

included English studies evaluating breast, colorectal, ovarian, or prostate cancers. Study designs 

were restricted to systematic review, experimental and diagnostic types. Populations were 

limited to those unselected for cancer risk. Interventions were limited to collection of cancer 

FHx; primary and/or secondary prevention interventions for breast, colorectal, ovarian, and 

prostate cancers. 

Results: Accuracy of models. Seven eligible studies evaluated systems based on the Gail model, 

and on the Harvard Cancer Risk Index. No evaluations demonstrated more than modest 

discriminatory accuracy at an individual level. No evaluations were identified relevant to ovarian 

or prostate cancer risk. 

Efficacy of preventive interventions. From 29 eligible systematic reviews, seven found no 

experimental studies evaluating interventions of interest. Of the remaining 22, none addressed 

ovarian cancer prevention. The reviews were generally based on limited numbers of randomized 

or controlled clinical trials. There was no evidence either to support or refute the use of selected 

chemoprevention interventions, there was some evidence of effectiveness for mammography and 

fecal occult blood testing. 

Uptake of intervention. Three studies evaluated the impact of FHx-based risk information on 

uptake of clinical preventive interventions for breast cancer. The evidence is insufficient to draw 

conclusions on the effect of FHx-based risk information on change in preventive behavior. 

Potential harms of FHx taking. One uncontrolled trial evaluated the impact of FHx-based 

breast cancer risk information on psychological outcomes and found no evidence of significant 

harm.

Conclusions: Our review indicates a very limited evidence base with which to address all four of 

the research questions: 1) the few evaluations of cancer risk prediction models do not suggest 

useful individual predictive accuracy; 2) the experimental evidence base for primary and 

secondary cancer prevention is very limited; 3) there is insufficient evidence to assess the effect 

of FHx-based risk assessment on preventive behaviors; and 4) there is insufficient evidence to 

assess whether FHx-based personalized risk assessment directly causes adverse outcomes. 

Contents 

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

Evidence Report............................................................................................................................ 9 

Chapter 1. Introduction ................................................................................................................. 11 

Background............................................................................................................................... 11 

The Potential of Family History Information in Preventing Cancer..................................... 11 

Evaluating Family History for use in the Prevention of Cancers ......................................... 14 

Risk Stratification ................................................................................................................. 15 

Effectiveness of Cancer Risk Reduction Interventions ........................................................ 16 

Scope and Purpose of the Systematic Review .......................................................................... 17 

Chapter 2. Methods....................................................................................................................... 21 

Analytic framework .................................................................................................................. 21 

Search Strategy ..................................................................................................................... 22 

Eligibility Criteria ................................................................................................................. 22 

Eligibility Criteria for Research Q1:..................................................................................... 23 

Eligibility Criteria for Research Q2...................................................................................... 24 

Eligibility Criteria for Research Q3...................................................................................... 26 

Eligibility Criteria for Research Q4:..................................................................................... 27 

Study Selection ..................................................................................................................... 29 

Data Extraction ..................................................................................................................... 30 

Quality Assessment and Peer Review................................................................................... 30 

Summarizing our Findings: Descriptive and Analytic Approaches ......................................... 30 

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

Research Q1: Which Risk Stratification Algorithms or Guidelines Delineate Risk Accurately, 

and in a Clinically Meaningful Way? ....................................................................................... 31 

General Approach ................................................................................................................. 31 

Studies Reviewed.................................................................................................................. 31 

Outcomes .............................................................................................................................. 32 

Gail Model ............................................................................................................................ 32 

Modified Gail Model ............................................................................................................ 32 

CARE Model ........................................................................................................................ 33 

Harvard Cancer Risk Index................................................................................................... 33 

Conclusion ............................................................................................................................ 34 

Research Q2: For Which Behaviors and Clinical Preventive Services is There Evidence of 

Benefit in Terms of Actual Reduction of Disease Risk, and What Harms, if any, Have Been 

Identified? ................................................................................................................................. 34 

General Approach ................................................................................................................. 34 

Studies Reviewed.................................................................................................................. 34 

Breast Cancer........................................................................................................................ 35 

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

Prostate Cancer ..................................................................................................................... 39 

vii
Quality Assessment of Studies.............................................................................................. 41 

Conclusion ............................................................................................................................ 41 

Research Q3: For Those Interventions Identified as Being Based on Reasonable Evidence, 

What is the Evidence That Providing Information on Risk Status Results in Behavior Change 

or Increased Uptake of Services on the Part of Individual Patients?........................................ 42 

General Approach ................................................................................................................. 42 

Studies Reviewed.................................................................................................................. 43 

Outcomes .............................................................................................................................. 44 

Quality Assessment of Studies.............................................................................................. 44 

Conclusion ............................................................................................................................ 45 

Research Q4: What are the Harms or Risks to Individual Patients That may Result From the 

Collection of Family History Information in Itself, and/or the Provision of Family HistoryBased Risk Information?........................................................................................................... 46 

General Approach ................................................................................................................. 46 

Studies Reviewed.................................................................................................................. 46 

Outcomes .............................................................................................................................. 46 

Conclusion ............................................................................................................................ 47 

Chapter 4. Discussion ................................................................................................................... 77 

Risk Stratification Algorithms .............................................................................................. 77 

Cancer Prevention Interventions........................................................................................... 79 

Family History-Based Risk Assessment and Individual Preventive Behaviors ................... 82 

Direct Harms or Risks From Family History-Based Risk Assessment ................................ 82 

Limitations ................................................................................................................................ 83 

Conclusions............................................................................................................................... 84 

Reference List ............................................................................................................................... 87 

Tables 

Table 1. Pooled relative risk estimates (95% confidence intervals) for cancers of interest ....... 12 

Table 2. Elements and key components of evaluation framework for family history as screening 

tool ................................................................................................................................ 15 

Table 3. Family history-based risk stratification guidelines for breast, ovarian, colorectal, 

prostate cancers............................................................................................................. 16

Table 4. Details of risk prediction models.................................................................................. 48 

Table 5. Evaluations of risk prediction models .......................................................................... 50 

Table 6. Target interventions for review..................................................................................... 56 

Table 7. Breast cancer preventive interventions......................................................................... 57 

Table 8. Colorectal cancer preventive interventions................................................................... 61 

Table 9. Prostate cancer preventive interventions ...................................................................... 66 

Table 10. Details of family history and personalized risk interventions ...................................... 70 

Table 11. Evaluations of family history and personalized risk..................................................... 72 

Table 12. Harm/risk of family history collection......................................................................... 76 

Figures 

Figure 1. Family history-based primary care activities ................................................................ 13 

viii
ix

Figure 2. Analytical framework for the research questions evaluated in this review................... 21 

Figure 3. Flow of studies to final number of eligible studies ....................................................... 29 

 

Appendixes 

Appendix A: Detailed Search Strategies 

Appendix B: Forms and Guides 

Appendix C: Studies Retained But Not Extracted 

Appendix D: List of Excluded Studies 

Appendix E: Partners, 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/famhistory/famhist2.pdf. 
Executive Summary 

Family history reflects the combined influences of genetics, environmental exposures, and 

behaviors within families,1 and is a risk factor for some clinically important chronic diseases 

such as cardiovascular disease, diabetes mellitus, stroke, and several cancers.2,3 Family history 

reflects genomic, social and environmental risk which is shared between relatives. This 

‘compressed information’4 may provide predictive information independent of other known risk 

factors. 

Individual risk stratification systems based on family history may carry valuable predictive 

information for individual patients, but they need to be validated for application in routine 

practice. The usefulness of family history-based risk stratification systems in disease prevention 

depends on (a) accurate reporting and capture of family history information, (b) valid methods of 

risk classification, (c) effective preventive interventions to manage disease risk, and (d) evidence 

that the use of family history information provides incremental net benefit over and above nonfamily history-based alternative approaches. With the exception of accuracy of reporting, this 

systematic review is designed to inform all of these issues. 

Scope and Purpose of the Systematic Review 

This report, which builds on a previous evidence report5 on the topic of tools for collecting 

and interpreting family history information, addresses the clinical utility of routinely using 

family history information in risk assessment and prevention for breast, ovarian, colorectal, and 

prostate cancers in primary care. The specific research questions are: 

1. Which risk stratification algorithms or guidelines delineate risk accurately, and in a clinically 

meaningful way? 

2. For which behaviors and clinical preventive services (‘interventions’) is there evidence of 

benefits in terms of actual reduction in disease risk, and what harms, if any, have been 

identified? 

3. For those interventions identified as being based on reasonable evidence, what is the 

evidence that providing information on risk status results in behavior change or increased 

uptake of services on the part of individual patients? 

4. What are the harms or risks to individual patients that may result from the collection of 

family history information in itself, and/or the provision of family history-based risk 

information? 

These questions represent the links in the chain between taking family history and producing 

benefit: Does family history predict future risk of cancer? If so, are there interventions to reduce 

this risk, and do they also carry their own risks? Does a family history-based approach lead to 

higher uptake of preventive interventions? Are there any direct harms which arise from a family 

history-based approach? 

This review’s focus is therefore firmly on the application of family history taking from 

general populations under the care of primary care providers such as family physicians, 

internists, nurse practitioners, and obstetricians. We sought to examine the capture and use of 

1
family history information as an activity practiced in primary care, where patients are not preselected for risk, and where the approach to capturing information is heavily influenced (often 

constrained) by contextual factors,6

 and where the preventive interventions available are those 

that can be recommended by a primary care practitioner. This is distinctly different from clinical 

genetics assessment, where the central focus is on extensive family history capture, validation, 

and assessment, where the patient population is usually pre-selected for high risk status. 

Methods 

Standard systematic review methodology was employed. MEDLINE®, EMBASE®, 

CINAHL®, Cochrane Central®, Cochrane Database of Systematic Reviews, and PsycINFO were 

searched from 1990 to June 2008 inclusive. Cancer guidelines and recommendations were 

searched from 2002 forward and systematic reviews from 2003 to June 2008. 

Eligibility criteria included English studies evaluating breast, colorectal, ovarian, or prostate 

cancers. Study designs varied by question, but were restricted to systematic reviews of 

effectiveness (Question 2), and experimental (Questions 3 and 4) and diagnostic evaluation 

(Question 1) types. Populations were limited to those unselected for cancer risk. Interventions 

were the structured/systematic collection of family history (Questions 1, 3, and 4) and primary or 

secondary cancer prevention (screening) interventions (Question 2). The outcomes were disease 

incidence or proxy (Questions 1 and 2), uptake of recommended preventive interventions 

(Question 3), and harms (e.g., psychological distress) (Question 4). 

Results 

Our comprehensive search yielded 10,644 unique citations; from these 9,765 were excluded 

as they were not an English language publication, not on the cancers of interest, or on topic for 

any of the four research questions. The remaining 879 citations were screened at full text and 

from these a total of 12 primary studies and 29 systematic reviews were eligible. 

Research Q1: Which Risk Stratification Algorithms or 

Guidelines, Delineate Risk Accurately and in a Clinically 

Meaningful Way? 

 General approach. The purpose of this question was to establish whether family historybased risk stratification systems (of any kind) could accurately predict risk in individual patients. 

We reviewed published studies that examined the discriminatory accuracy of models 

(algorithms, guidelines) that used family history information to predict individual risk of breast, 

ovarian, colorectal or prostate cancer. To be eligible, a model had to incorporate specified family 

history information (either alone or with other personal or clinical information which would be 

routinely available on all patients to a primary care practitioner), and validation data in a defined 

general population had to be presented. The main outcome of interest was discriminatory 

accuracy, which reflects the proportion of individuals correctly classified by the tool with respect 

to actual disease incidence. This was variously presented as a concordance statistic, the area 

under the curve in receiver operating characteristic (ROC) analyses, or correlation coefficient, 

and reflects the usefulness of the model for use in the assessment of individual patients. 

2
Findings. Eight evaluation studies were identified as eligible after full text review.7-14 All 

tools except one were designed for breast cancer risk assessment. The breast cancer tools were 

all generally related to the original Gail model,15 including the model developed from the 

Contraceptive and Reproductive Experiences Study (the CARE model7

). The Harvard Cancer 

Risk Index16 (HCRI) was developed for application to a number of cancers, but an eligible 

validation study was identified only for colon cancer. No eligible studies were identified of tools 

based strictly on family history information alone. 

The original evaluation of the Gail model was conducted in a predominantly white U.S. 

female population,8

 and reported discriminatory accuracy in terms of a Pearson correlation 

coefficient (0.67). The other breast cancer models were evaluated in white,9

 “diverse”,13 African 

American,7,10 and Italian11,12 populations. These studies reported concordance statistics in the 

range of 0.55-0.59, indicating very modest discriminatory accuracy. 

 The HCRI was evaluated for prediction of colon cancer14 in secondary analyses of cohort 

data, and reported concordance statistics of 0.67 and 0.71 for women and men, respectively. This 

suggests moderate discriminatory accuracy (67 and 71 percent correct prediction of eventual 

cancer status respectively, 50 percent being that expected by chance alone). 

Research Q2: For Which Behaviors and Clinical Preventive 

Services is There Evidence of Benefit in Terms of Actual 

Reduction in Disease Risk, and What Harms, if any, Have 

Been Identified? 

General approach. The purpose of this question was to establish the link between stratifying 

cancer risk and being able to intervene to alter that risk, and not to conduct an exhaustive review 

of the extensive literature around cancer risk factors. We therefore evaluated published 

systematic reviews on a range of interventions which are generally recommended as part of 

cancer risk reduction strategies in primary care settings. Where multiple reviews addressing the 

same intervention were identified, we selected the most recent or most comprehensive for 

reporting, and considered differences in methodological quality.17

Findings. Twenty-nine systematic reviews were retained after full text review, addressing 

four chemoprevention interventions (antioxidant supplementation, calcium supplementation, 

non-steroidal anti-inflammatory drugs (NSAIDS), but not COX-2 inhibitors and statins) and five 

screening interventions (breast self-examination (BSE), screening mammography, fecal occult 

blood testing (FOBT), flexible sigmoidoscopy (FS), and prostate specific antigen (PSA) for three 

cancers (breast, colorectal, prostate). No reviews were identified for several interventions of 

interest, and none were relevant to ovarian cancer prevention. 

Data were extracted from the 10 reviews that represented the most comprehensive, up-todate, and high quality evidence.18-27 Of the remainder where data were not abstracted, 12 

reported overlapping data,28-39 five did not identify primary intervention studies despite these 

being designed to do so,40-44 and two did not report usable data.45,46 

Overall quality assessment suggested low risk for bias, the main area of weakness being 

failure to describe adequate control of bias in study selection.18-20,22,23,27 Other issues were 

incomplete description of search methods,23,27 failure to describe criteria for assessing the 

validity of primary studies,20,25,26 and failure to cite the validity assessments of included 

studies.20,26

3
Breast Cancer 

Five systematic reviews synthesized evidence on chemoprevention (antioxidants and statins) 

and screening (breast self-examination (BSE) and screening mammography). 

Antioxidants. One review18 evaluated supplements that contained any combination of ßcarotene, vitamin C, vitamin E, selenium, zinc, and other antioxidants, and concluded no 

evidence of a protective effect of any combination against breast cancer (RR 1.00, 95 percent CI 

0.90-1.09) at one year followup. A second review19 examined vitamin E alone or in any 

combination in three high quality randomized controlled trials (RCT) and concluded no evidence 

of a reduction in breast cancer incidence (RR 0.99, 95 percent CI 0.90-1.10). 

Statins. One review,20 suggested that statins appeared to confer neither a protective nor a 

harmful effect on breast cancer incidence (RR 1.01, 95 percent CI 0.79-1.30). 

BSE. One review21 showed no impact of BSE on breast cancer mortality (RR 1.05, 95 

percent 0.98-1.14). 

Screening mammography. The most recent comprehensive review,22 suggested that 

screening mammography was associated with reduced breast cancer mortality at 13 years (RR 

0.80, 95 CI 0.73-0.88), although concerns were raised about inadequate bias control in some 

primary trials. No effect on overall mortality was noted (RR 1.00, 95 percent CI 0.96-1.04). 

Colorectal Cancer 

Six reviews evaluated interventions in colorectal cancer (CRC) prevention, four on 

chemoprevention (antioxidants, NSAIDS, statins) and two on screening (fecal occult blood 

testing (FOBT) and flexible sigmoidoscopy (FS)). 

Antioxidants. One review18 evaluated supplements which contained any combination of ßcarotene, vitamin C, vitamin E, selenium, zinc, and showed no evidence of a protective effect 

against CRC incidence (RR 1.00, 95 percent CI 0.90-1.10). A second review19 evaluated vitamin 

E given in any combination and found no evidence of an effect on CRC incidence (RR 0.95, 95 

percent CI 0.81-1.12). 

NSAIDS. One review evaluated low dose ASA,23 and found no evidence of an effect on 

CRC incidence (RR 1.02, 95 percent CI 0.84-1.25), CRC mortality (RR not reported) or 

adenoma incidence (RR 0.85, 95 percent CI 0.68-1.1) at 5 years. 

Statins. One review20 showed neither a protective nor harmful effect of statins on CRC 

incidence (pooled RR 1.02, 95 percent CI 0.89-1.16) or CRC mortality (RR 0.33, 95 percent CI 

0.07-1.63). 

FOBT. One review24 examined FOBT (guaiac or immunochemical) in studies of at least two 

rounds of screening were compared with no screening. A statistically significant effect of 

screening on CRC mortality was observed (RR 0.84, 95 percent CI 0.78-0.90), and no effect on 

all-cause mortality (RR 1.00, 95 percent CI 0.99-1.01). 

FS. A single review25 examined the evidence for FS in CRC screening, identifying a single 

RCT comparing FS plus FOBT against FOBT alone. No statistically significant effect was found 

on CRC mortality or incidence (RR 0.78, 95 percent CI 0.36-1.73 and 1.37, 95 percent CI 0.88-

2.15, respectively). 

4
Prostate Cancer 

Five reviews synthesized evidence in relation to prostate cancer prevention: four relating to 

chemoprevention (antioxidants, calcium, and statins) and one relating to screening (prostatespecific antigen (PSA) with digital rectal examination (DRE) and trans-urethral ultrasound 

(TRUS) biopsy). 

Antioxidants. One review18 evaluated supplements that contained any combination of ßcarotene, vitamin C, vitamin E, selenium, zinc, and other antioxidants. The pooled analysis of all 

antioxidants showed no effect on prostate cancer incidence (RR 0.87, 95 percent CI 0.74-1.02), 

and a reduced risk associated with vitamin E specifically (RR 0.82, 95 percent CI 0.67-0.99). A 

second review19 of vitamin E in any combination showed a negative association with prostate 

cancer incidence (RR 0.85, 95 percent CI 0.74, 0.96). 

Calcium. One review evaluated calcium supplementation and prostate cancer risk,26 where 

this was a secondary outcome in a single colorectal adenoma prevention trial.47 It suggested a 

statistically significantly lower incidence of prostate cancer in the supplement group until 2 years 

after supplementation was discontinued (rate ratio 0.52, 95 percent CI 0.28-0.98), at which point 

the risk in both groups converged. 

Statins. One review20 examined the effectiveness of statins on prostate cancer. The results 

indicated that statins appeared to neither increase nor decrease the risk of prostate cancer 

incidence or mortality (RR 1.00, 95 percent CI 0.85-1.17 and RR 0.99, 95 percent CI 0.14-7.01, 

respectively). 

PSA-based screening. One review27 examined the effectiveness of PSA-based population 

screening (with DRE and TRUS biopsy) in two trials, one with an annual and the other a three 

times yearly, screening cycle. No statistically significant impact of screening on prostate cancer 

mortality was found (RR 1.01, 95 percent CI 0.80-1.29). 

Research Q3: For Those Interventions Identified as Being 

Based on Reasonable Evidence, What is the Evidence That 

Providing Information on Risk Status, Results in Behavior 

Change or Increased Uptake of Services on the Part of 

Individual Patients? 

General approach. The focus of this question was behavior: whether giving people 

personalized risk advice based on their family history would lead to a higher adherence with 

preventive recommendations. We evaluated intervention studies in which the outcomes were 

actual risk-reduction behavior, focusing on interventions that were considered standard of care 

when the primary study was conducted. 

Findings. Three studies48-50 were eligible, all focusing on uptake of screening interventions 

for breast cancer as the target behavior. Two were randomized controlled trials49,50 and examined 

different levels of personalization of risk information. The third48 was an uncontrolled beforeafter study. 

One trial48 showed a borderline statistically significant difference (P = 0.05) in 

mammography uptake (about 8 percent) between intervention and control groups. The other two 

studies were null. The community pharmacy study46 was the only one to examine other 

behaviors, and showed a statistically significant increase in self-reported BSE, but not CBE. 

5
Research Q4: What are the Harms or Risks to Individual 

Patients That may Result From the Collection of Family 

History Information in Itself, and/or the Provision of Family 

History-Based Risk Information? 

General approach. The purpose of this question was to identify whether the process of 

capturing family history and feeding back personalized risk, in and of itself, was associated with 

identifiable harms. We reviewed published intervention studies which examined the direct 

impact of family history-based risk information on quality of life, psychological, and social 

impact, where these could be directly attributed to this intervention and not subsequent 

investigations or preventive activities. 

Findings. One eligible study was identified,51 an uncontrolled before-after study designed to 

evaluate the psychological impact of providing family history information and receiving a 

personalized risk assessment for breast cancer. In all participants, no statistically significant 

change in anxiety or cancer worry between baseline and followup was observed. In participants 

whose risk assessment indicated “population risk”, a small reduction in self-perceived risk was 

observed (P<0.01). In participants who required further assessment (‘true’ high risk and ‘false 

positive’ groups), higher baseline cancer risk perception scores were observed compared with the 

group assessed as population risk (P<0.001 for ‘higher risk’ group and P=0.003 for ‘false 

positive’ group). 

Discussion and Conclusions 

The purpose of this review was to establish the evidence base to answer the question, “In 

primary care settings, and in relation to breast, ovarian, colorectal or prostate cancers, would the 

routine use of family history-based risk assessment be likely to lead to net health benefits?” We 

identified a very limited evidence base for all four of the research questions. 

While there are a number of FHx-based cancer risk stratification systems, no evaluations 

have been published of any based only on FHx information. Of those models which include FHx 

information along with other clinical variables, published validations suggest good 

epidemiological calibration but no more than modest individual discriminatory accuracy. The 

models evaluated were not necessarily developed for general clinical use. 

The experimental evidence base, represented in published systematic reviews, for primary 

and secondary cancer prevention in general populations is very limited. The most consistent 

evidence supports screening mammography and FOBT-based colorectal screening strategies, 

with equivocal evidence for vitamin E and calcium in reducing the risk of prostate cancer. The 

review likely did not include some experimental evidence for interventions which have not been 

examined in systematic reviews, but which would be relevant to the main study questions. 

There is insufficient evidence to assess the effect of FHx-based risk assessment on preventive 

behaviors. Very few trials have been conducted, and none in settings resembling routine primary 

care practice. There is also insufficient evidence to assess definitively whether FHx-based 

personalized risk assessment directly causes adverse outcomes; the results of the single study 

available indicate the need to take into account baseline psychological status and risk perception 

in assessing the impact of FHx-based risk information. 

6
Conclusions 

1. The evidence for the predictive accuracy of algorithms in primary care populations was very 

limited. Although many tools were identified that incorporated some family history information, 

no evaluations of solely family history-based tools. The tools on which it was possible to 

comment related mainly to breast cancer. 

Recommendations for future research: 

• The actual performance of tools based only on family history should be formally 

examined in primary prospective studies, and/or in secondary analysis of large cohort 

studies. 

• The performance of individual family history components of different risk 

stratification models which use a wider range of factors (including those examined in 

this report) should be examined separately from the non-family history components, 

in order to determine whether they provide sufficient predictive power in the absence 

of the non-family history factors. 

• For clinical relevance, the focus of validation should be discriminatory accuracy at 

the individual patient level. 

• More definitive evaluation should examine the effect on health outcomes when risk 

stratification systems are used in combination with preventive interventions, in actual 

practice settings. This cannot be done with secondary analyses of observational data 

and requires well-designed intervention studies. 

2. The evidence establishing the efficacy of interventions for primary and secondary prevention 

based on systematic reviews of randomized or controlled clinical studies in unselected 

populations is very limited. Interventions for which there were reviews include chemoprevention 

(antioxidants, calcium, NSAIDS, and statins) and screening interventions (BSE, mammography, 

FBOT, FS, and PSA) for breast, colorectal and prostate cancers. No reviews were found for 

ovarian cancer. It is likely that this review excluded effectiveness data available from RCTs of 

interventions which have not yet been the subject of systematic reviews. 

Recommendations for future research: 

• The large amount of evidence on potential primary cancer preventive interventions 

obtained from observational studies of cancer risk factors should continue to be 

further evaluated in well-designed randomized controlled trials. 

• Further systematic reviews should be conducted to examine the full range of 

potentially preventive interventions 

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 family history and using it to personalize risk of breast, ovarian, 

colorectal or prostate cancer. 

Recommendations for future research: 

• Well-designed trials are required that compare family history-based, personalized risk 

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

risk levels (including population risk). 

7
8

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

from the routine practice of taking family history and using it to personalize risk information. 

Recommendations for future research: 

• Trials of family history taking as an intervention should include capture of data to 

examine the full range of potential impacts on individuals. Baseline data on 

psychological status should be captured so that this can formally be adjusted for in 

outcome analyses. 

5. Research on the use of family history tools, risk stratification systems, and family historybased personalized prevention advice should take into account evidence on the factors likely to 

promote their effective use in practice, such as the educational needs of primary care 

practitioners and issues which act as barriers or constraints to their implementation in practice. 
Evidence Report 
 
Chapter 1. Introduction 

Background 

The Potential of Family History Information in Preventing Cancer 

Family history has always been a core tool in medical practice. A person’s family history 

reflects the combined influences of genetics, environmental exposures, and behaviors within 

families.1

 A large number of reports demonstrate that a positive family history is a risk factor for 

many chronic diseases of clinical importance, including cardiovascular disease, diabetes 

mellitus, stroke, and several cancers.2,3 The greater the number of relatives affected by a 

disorder, the younger their ages of onset, and the closer the relationship to the individual in 

question, the more likely it is that the family’s disease experience has a genetic basis. However, 

given the low population prevalence of genetic forms of common, complex disorders, a 

screening approach based on identifying fairly extreme family histories offers very limited public 

health or clinical utility in practice. 

Historically, the practice of clinical genetics has been largely predicated on detecting 

individuals marked out by membership in families with unusual patterns of disease, and who are 

at significantly elevated individual risk as a result of rare genetic disorders that have relatively 

high penetrance. The alternative approach, which is the focus of this review, is to recognize that 

family clustering of disease risk reflects combinations of lower penetrance, and moderate risk 

alleles which are reasonably common within a population. The latter example, a high prevalence 

of people with slightly or moderately elevated inherited disease risk, would lead to a much 

higher total disease burden within a population than that associated with a low prevalence of 

people at very high risk.52 Under the right circumstances, a ‘genomic test’ – such as the presence 

of particular family history characteristics - could have a significant positive predictive value. 

Several years ago, Yoon and colleagues1 illustrated this point. They demonstrated how even 

fairly simple family history information could be used to clarify the risk of a number of common, 

complex disorders. Based on published data, they suggested that a healthy 23 year old man could 

have the following lifetime risks of: 

• 60 percent for cardiovascular disease (based on one male first degree relative (1DR) 

diagnosed after age 60) 

• 50 percent for colorectal cancer (based on two 1DRs diagnosed before age 50); and 

• 30 percent for type 2 diabetes (based on one 1DR diagnosed after age 60 

Importantly, their risk prediction was based on family history information which would not 

be considered extreme. This application of family history information complements the vision of 

‘personalized medicine’ which physician-geneticist Francis Collins M.D., PhD., predicted 

would be available in 2010, in the form of DNA-based genome profiling tests.53 While recent 

research indicates that such profiling is possible in principle,54 it is evident that this is not yet a 

technology ready for routine implementation in health care.52,55 Until such time, family history 

represents a potential source of useful predictive information already available to any health care 

provider. 

 11
Discussing the role of family history in coronary heart disease risk, Kardia and colleagues 

describe the family history as “compressed information” which integrates risks arising from 

shared genomic components, and social and physical environments.4

 They expand: 

 “For, example, we know that parents and children share exactly half their genes. This 

translates practically into sharing one copy of the 30,000 to 50,000 genes estimated to be 

in the human genome in the nucleus of each nucleated cell in the human body. ... it is 

quite possible that even with our ability to measure hundreds and thousands of genes and 

environments we may find that family history is the best, low-cost way to identify the atrisk subgroups in the population. This will be especially true if gene-gene and geneenvironment interactions play a major role in determining risk of future disease.” 

This perspective is supported by the work of Butterworth,3 who recently conducted a 

comprehensive meta-analysis of the risk conferred by family history for a number of common, 

complex disorders, including the cancers of interest in this review. Table 1 summarizes his 

findings for colorectal, breast, ovarian, and prostate cancer. 

Table 1. Pooled relative risk estimates (95% confidence intervals) for cancers of interest3

Cancer >1 1DR >2 1DRs Age 

cut-off 

younger, 

older 

Younger 

affected relative 

Older affected 

relative 

Colorectal 2.24 

(2.06, 2.43) 

3.97 

(2.60, 6.06) <50, ≥50 

3.55 

(1.84, 6.83) 

2.18 

(1.56, 3.04) 

Breast 1.80 

(1.70, 1.91) 

3.01 

(2.46, 3.69) <40, >60 

2.22 

(1.71, 2.87) 

1.55 

(1.38, 1.74) 

Ovarian 2.85 

(2.41, 3.37) 

14.74 

(5.78, 37.60) <50, ≥50 

3.98 

(2.53, 6.26) 

2.90 

(2.10, 4.01) 

Prostate 2.42 

(2.25, 2.60) 

4.27 

(3.13, 5.84) <60, ≥60 

2.91 

(2.12, 4.01) 

1.88 

(1.47, 2.40) 

1DR=first degree relative 

These meticulous analyses provide direct evidence to support the association between family 

history and risk of cancer even when family history is captured in a less specific or extensive 

way than is the case in a specialist genetics consultation. 

In order to understand the specific nature of family history information which might be most 

useful in primary care settings, it is useful to consider how family history data may serve 

different purposes. Figure 1 maps out different contexts for family history taking in primary care 

against the general locus of clinical management (primary care versus specialist referral) if 

elevated risk is identified. It demonstrates how the goal of family history taking may include, but 

is most definitely not limited to, identifying rare, high risk disease patterns in families which 

warrant referral for formal genetic evaluation (domain A). Domain B represents systematic 

screening of general patient populations for a defined range of familial or genetic diseases. 

Domain C represents the assessment of disease-specific family history information with other 

risk factor data in the assessment of chronic disease risks in individual patients. In all three 

domains (A, B, C), a primary care practitioner may be the key provider who captures the family 

history data; however, the drivers for capturing such information, and the likely decisions that 

will follow, vary across the three domains and extend beyond the possible identification of 

classical genetic disorders. 

 12
 Figure 1: Family history-based primary care activities 

 

a priori suspicion of specific disease 

risk 

Low High 

Primary 

carebased 

preventive 

strategies 

Specialist 

genetics 

referral 

A 

Suspected genetic risk, 

highly targeted risk 

assessment 

C 

Individual chronic disease 

 risk assessment 

B 

Systematic 

populationbased 

screening 

or case 

finding 

 Clinical Management Approach 

Mixed 

Domain A represents the assessment of a patient in whom clinical suspicions of an inherited 

disorder or predisposition have arisen, for example in response to concerns about several 

relatives affected by cancer. In this situation, the main clinical goal would be to assess whether 

the individual met the criteria for referral for specialist genetics assessment and/or genetic 

testing. A family history ‘tool’ in this situation would be represented by guidelines for genetic 

referral or testing. Here, the focus would be on capturing specific family history information 

which might be rather extensive and specific, requiring attention to, for example, different 

combinations of diseases in the family, the lineage of affected relatives, and so forth, as 

illustrated in the Bethesda criteria for non-polyposis colorectal cancer.56

Domain B might typically represent a periodic health assessment in an otherwise healthy 

individual, where there would be no suspicion of underlying genetic disease and no particular 

indications of illness or disease susceptibility. Here, the goal would be to conduct a broad brush 

assessment across a range of common disorders, to identify issues which warrant further probing 

by the primary care practitioner. The most useful family history tool might incorporate a limited 

range of the most sensitive family history markers or “red flags” across a range of disorders, in 

the expectation that more detailed information would be collected for those conditions where an 

indicator item was positive. 

In domain C, the primary care practitioner’s goal would be to incorporate family history with 

other clinical and personal information to assess future risk of a specific chronic disease, with a 

view to ordering further investigations and advising on appropriate risk reduction strategies. In 

this situation, the focus would be on family history items which were either independently highly 

predictive of disease risk, or added useful incremental predictive value to other, established risk 

factors. A family history “tool” in this context might actually consist of a short set of questions 

within a more comprehensive disease-specific risk assessment guideline. An example of this 

approach would be the incorporation of information on parental history of myocardial infarction 

in the National Cholesterol Education Program III guidelines.57 

 13
These three domains are clearly not mutually exclusive. However, this approach illustrates 

that the demands of extensiveness and specificity of the type of information that is necessary is 

not uniform across all contexts. Until comprehensive and current family history information is 

available for patients through, for example, electronic records systems, a primary care 

practitioner’s approach to family history-taking may be influenced by external constraints (e.g., 

time), their prior assessment of the patient’s risk of disease, and the way in which the 

information will actually be used for decisionmaking. 

Although this report borrows from the language and concepts of genetics and genomics (see 

below), its approach reflects the perspective on family history exemplified particularly by 

domain C described above. Its focus is on the utility of using family history information to 

stratify the risk of common, complex diseases in individuals who are not specifically selected for 

suspicion of high genetic risk. 

Evaluating Family History for use in the Prevention of Cancers 

The usefulness of family history stratification systems as predictive tools for common, 

chronic diseases can be approached using an evaluation framework originally developed by the 

Secretary’s Advisory Committee on Genetic Testing.58 This framework has four elements (1) 

analytic validity; (2) clinical validity; (3) clinical utility; and (4) ethical legal and social 

implications of using a test. It has been further developed for application to the evaluation of 

family history information in disease prevention (see Table 2 for definitions).59 Put another way, 

the line of evidence between family history and individual and population benefit requires 

answers to the following questions: 

(a) Does a positive family history (however defined) predict future risk of cancer in an 

individual patient sufficiently accurately to be useful in a clinical setting? 

(b) If so, are there interventions available which reduce the risk of cancer? Do these 

interventions also carry risks? 

(c) If there are interventions which help prevent cancer, does information on family historybased disease risk mean a person is more likely to adhere to them (compared with 

advice which is not based on knowledge of family history)? 

(d) Are there any direct harms which arise from the process of taking a family history and 

feeding back personalized risk based on family history? 

In terms of efficient health care resource use, it is also legitimate to examine the incremental 

benefits and costs associated with capturing and using family history information, whether it 

substitutes for, or adds informational value to, other risk factor information, and whether it is 

easier and/or cheaper to obtain. 

 14
Table 2. Elements and key components of evaluation framework for family history as screening tool 

[reproduced from Yoon, Scheuner, and Khoury 2003]59

Element Definition Components 

Analytic validity An indicator of how well a test or tool 

measures the property or characteristic 

(disease status among relatives) that it 

is intended to measure 

Analytical sensitivity 

Analytical specificity 

Clinical validity A measurement of the accuracy with 

which a test or tool identifies or predicts 

a clinical condition 

Clinical sensitivity 

Clinical specificity 

Positive predictive value 

Negative predictive value 

Clinical utility Degree to which benefits are provided 

by positive and negative test results 

(presence and absence of family 

history for disease) 

Availability of effective 

interventions 

Health risks and benefits 

Economic assessment 

Ethical, legal, and social 

implications 

Issues affecting data collection and 

interpretation that might negatively 

impact individuals, families, and society 

Stigmatization 

Discrimination 

Psychological harms 

Risks to privacy and 

confidentiality 

Yoon P.W., Scheuner M.T., Khoury M.J. Research priorities for evaluating family history in the prevention 

of common chronic diseases. Am J Prev Med 2003;23(2)128-135. Used with permission. 

In a previous effectiveness report,5

 evidence regarding the accuracy of reporting by 

individuals of their family history of breast, ovarian, colorectal, and prostate cancer was 

synthesized, and a large number of family history tools and family history-based risk assessment 

tools identified and reviewed. The current review is designed to inform issues (a) to (d) above, 

which address the issues of clinical validity and, in part, clinical utility. 

Risk Stratification 

A number of risk classification systems exist, generally in the form of guidelines or 

algorithms developed to assist in decisionmaking around referral to genetic services or genetic 

testing (e.g., Rodriguez-Bigas56). Few risk stratification systems have been developed 

specifically for direct application in primary care, with a focus on recommending behavior 

changes and/or preventive clinical interventions in which referral for genetic counselling would 

be relevant for only a small sub-group of patients. One such system is that proposed by Scheuner 

and colleagues60 who, in a paper predating Butterworth’s analysis,3

 used available 

epidemiological data61-70 to define three risk strata for a number of complex disorders (Table 3). 

An approach like this has the merit of appearing practical for immediate and easy application in 

primary care settings, but further evaluation is necessary to determine its predictive ability for 

the disorders of interest (clinical validity). 

 

 15
Table 3. Family history-based risk stratification guidelines for breast, ovarian, colorectal, prostate 

 cancers60 

High risk 

1. Premature disease* in a 1DR 

2. Two affected 1DRs 

3. A 1DR with late/unknown onset of disease and an affected 2DR with premature disease from 

the same lineage 

4. Two 2DRs, maternal or paternal, with at least one having premature onset of disease 

5. Three or more affected maternal or paternal relatives 

6. The presence of a ‘moderate risk’ family history on both sides of the pedigree 

7. Pedigree demonstrating clustering of different primary cancers consistent with a family cancer 

syndrome 

Moderate risk 

1. A 1DR with late or unknown disease onset 

2. Two 2DRs from the same lineage with late or unknown disease onset 

Average (population) risk 

1. No affected relatives 

2. Only one affected 2DR 

3. No known family history 

4. Adopted individual with unknown family history 

Scheuner M.T., Wang S.J., Raffel L.J., Larabel S.K., Rotter J.I. Family history: a comprehensive genetic risk assessment method 

for the chronic conditions of adulthood. Am J Med Genet 1997;71(3):315-324. Used with permission of John Wiley & Sons, Inc. 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative * Breast, ovarian: premenopausal or ≤50 years; colorectal, prostate ≤50 years 

Effectiveness of Cancer Risk Reduction Interventions 

Even the most highly predictive and practical risk stratification system cannot change health 

outcomes unless effective cancer prevention interventions are available for patients at risk. 

While there is extensive epidemiological literature on a wide range of cancer risk factors, much 

of the evidence regarding cancer prevention is based on observational studies. Contradictory 

evidence has emerged when some apparently protective factors, identified through observational 

studies71-73 were associated with increased risk of cancer in experimental studies, as was the case 

for alpha-tocopherol.74 It is crucial that any assessment of the clinical utility of family historybased risk stratification take into account the highest quality evidence on the benefits and risks of 

recommended preventive interventions. 

Effect of family history taking on uptake of interventions. Assuming that proven 

preventive interventions are available, the question remains whether individualized, family 

history-based advice actually promotes uptake of such interventions by patients. Simplistically, it 

might be assumed that individuals would be more motivated to act on a health care provider’s 

advice if they know they are at higher than average risk. However, there is a body of literature in 

the area of predictive and predisposition genetic testing which cautions that knowledge of 

genetic risk might lead to fatalism in those at higher risk (failing to take up available 

interventions because of the ‘inevitability’ of disease) or complacency in those at average risk 

(failing to take up available interventions because of lower perceived personal risk - the 

‘certificate of health’ effect).75 Like any healthcare intervention, family history taking may incur 

incremental costs in time, energy, and money over and above standard care, therefore an 

examination of the incremental benefits is important. 

Risks inherent in family history-based risk assessment. No healthcare intervention should 

be assumed to be safe without formal assessment of harms as well as benefits. While family 

history taking is seen as a standard activity in all areas of healthcare, the systematic capture of 

 16
more extensive information, and its purposeful use in individual risk assessment, merits objective 

review. The ACCE framework58 emphasizes the assessment of both harms and benefits, and 

there is substantial literature that examines the impacts of predictive genetic tests beyond simple 

accuracy.76 While some guidelines77 suggest a cautionary approach, with cancer family history 

collection undertaken only in response to patients’ enquiries, many other observers argue that 

family history taking is an integral part of good clinical practice.78,79 Objective evidence on the 

prevalence of specific harms of family history taking, and of its use in advising patients about 

disease risk reduction, is necessary in order to clarify the appropriate level of caution to be 

exercised, and the types of situations in which patients might be most vulnerable to potential 

harms. 

Scope and Purpose of the Systematic Review 

This report is intended to build on a published evidence report focused on collection and use 

of family history for breast, ovarian, colorectal, and prostate cancers.5 The key questions for that 

project are available at: http://www.ahrq.gov/clinic/tp/famhisttp.htm. The current systematic 

review addresses four key research questions relating to the clinical validity and utility of 

routinely using family history information in risk assessment and prevention of breast, ovarian, 

colorectal, and prostate cancer in primary care, as follows: 

1. Which risk stratification algorithms or guidelines delineate risk accurately, and in a clinically 

meaningful way? 

2. For which behaviors and clinical preventive services (‘interventions’) is there evidence of 

benefits in terms of actual reduction in disease risk, and what harms, if any, have been 

identified? 

3. For those interventions identified as being based on reasonable evidence, what is the 

evidence that providing information on risk status results in behavior change or increased 

uptake of services on the part of individual patients? 

4. What are the harms or risks to individual patients that may result from the collection of 

family history information in itself, and/or the provision of family history-based risk 

information? 

Addressing these four key questions requires a focus on different types of evidence and 

different sets of literatures. The focus of key question (Q1) is not only on identifying family 

history-based risk prediction systems (which may be presented as guidelines, algorithms or other 

tools) suited to use in primary care, but also on assessing their actual predictive ability when 

applied to individual patients. This requires review of primary studies addressing discriminatory 

accuracy in cohorts representative of relevant general populations. Key question (Q2) asks 

whether effective cancer prevention interventions are available. While answering this question is 

an essential step in addressing the overall question of clinical utility of cancer family history 

taking, we note that the primary goal of this report is on family history taking, rather than 

evidence for cancer control per se. Given the considerable practical implications in attempting to 

synthesize the very extensive literature on cancer risk factors and prevention (see, for example, 

the reports by the World Cancer Research Fund26,45,46), the reasonable expectation that evidence 

reviews might be available for cancer prevention interventions which are considered standard of 

care, and direction from the sponsors of the report, the focus is therefore on reviewing systematic 

 17
reviews for primary and secondary (screening) cancer prevention. Key questions (Q3) and (Q4) 

are evaluative questions. Question 3 asks whether taking and using family history information is 

more likely to lead to desired behavior changes in patients than other approaches which do not 

use family history information. In addressing this question it is important to distinguish between 

studies which examine the behavior of people who have pre-existing perceptions of elevated 

disease risk because of living with a “family disease” from the clinical strategy of systematically 

capturing family history information and personalizing risk assessment for all patients, in order 

to promote adherence to recommended preventive behaviors. The possibility for confounding of 

the latter by the former cannot fully be addressed in observational studies, and steers the review 

towards examining evidence from well-designed intervention studies. The same issue applies in 

question (Q4), where adverse outcomes from the clinical strategy of taking and using family 

history information needs to be separated out from the psychological and social impacts of living 

with the implications of pre-existing perceived familial disease risk. 

As discussed above, the focus of this review is firmly on using family history information in 

a primary care context. This has driven the eligibility criteria for studies towards 

• study populations that resemble those in primary care – with an inherent range of disease 

risks but not selected because of suspicion of genetic disease 

• 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 

• cancer 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) 

Even within primary care, we recognize that there is an inevitable gradation (rather than a 

clear cut separation) between family history taking as a means to promote effective primary carebased disease risk assessment and management (domain C, Figure 1), and family history taking 

as a way of identifying individuals who may be at high genetic risk, where referral to specialist 

genetics services is warranted (domain A). We therefore sought to include studies examining 

family history taking as a generalist activity, and to exclude studies which focused on family 

history as part of a clinical genetics assessment. Thus, even though we recognize that family 

history taking is a core activity in specialist genetics, this review excludes literature where the 

focus is primarily on the assessment of genetically high risk patients in specialist settings. 

It is also important to emphasize that 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, with clustering around an “average” value (by definition). This criterion was 

adopted in an effort to reflect professional and patient decisionmaking in “typical” primary care 

contexts where patients with a wide range of risks (but mostly “average”) are encountered. Thus, 

it would be expected that a predictably small proportion of patients from an unselected 

population would be classified by a risk stratification system into a high risk category. This 

situation is distinctly different from those where patients and their providers already know or 

suspect that they are at high disease risk, by virtue of, for example, an uncommon pattern of 

familial disease, a positive genetic test result in a close relative, a previous diagnosis of the 

condition, or diagnosis of a pre-disease state. In short, populations unselected for high risk may 

include some high risk individuals whereas populations selected for high risk definitively exclude

 18
 19

average and low risk individuals. We suggest that it cannot be assumed that findings from 

“selected for high risk” studies are directly applicable to the general primary care context. 
 
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 cancer family history, and 

the outcomes of interest for each research question. Figure 2 shows the inter-relationships among 

the four research questions being addressed in this systematic review. Cancer family history is an 

important component of algorithms, models, and guidelines used to predict risk of cancer or gene 

mutation; we evaluated predictive accuracy outcomes of eligible algorithms, models, or 

guidelines in the first research question (Q1). A large number of interventions have been 

implemented to address primary and secondary prevention of the cancers of interest; our second 

research question evaluated the evidence from systematic reviews and evaluated outcomes of 

benefit and harm from these interventions (Q2). Following the collection of cancer family 

history, the uptake of these prevention and screening interventions was the outcome of interest 

for our third research question (Q3). Our final research question focused on the potential for 

harmful outcomes as a result of collecting family history (Q4). 

Figure 2. Analytic framework for the research questions evaluated in this review 

Collect Family 

History 

Models 

Predict 

Risk Interventions 

Outcomes 

Benefit 

Outcomes 

Harms 

Risk of 

Disease or 

Proxy 

Q4 

Q1 

Q2 

Q3 

Q2 

Uptake of 

Intervention

Risk Stratification 

 21
Search Strategy 

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

CINAHL®, Cochrane Controlled Trials Register (CCTR)® (Q1, Q3, Q4), Cochrane Database of 

Systematic Reviews (Q2), and PsycINFO (Q3). Years searched were 1990 to June 2008 

inclusive (Q1, Q3, and Q4). We searched for cancer guidelines and recommendations from 2002 

forward to ensure that the guidelines were reasonably current. We also searched the grey 

literature, including the National Clearing House for guidelines. Based on input from our 

Technical Expert Panel we searched the Guide to Community Preventive Services published by 

the CDC80 and other appropriate guidelines (e.g., U. S. Preventive Services Task Force 

recommendations for the prevention and screening interventions for the cancers of interest). 

Finally, we restricted the search for systematic reviews (Q2), from 2003 to June 2008 (Q2). 

As per the recommendations of our content experts, we reviewed the methods and content of the 

report “Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective” 

published by World Cancer Research Fund’ from American Institute for Cancer Research 

(updated for breast cancer only in Spring 2008).81 This report reflects an international initiative 

that has systematically reviewed the literature to evaluate the cancer prevention evidence for a 

range of interventions broadly including exercise and related behaviors, food and food 

supplements (including vitamins), and screening interventions for different types of cancer 

(including breast, ovarian, colorectal, and prostate cancers). Since this World Cancer Review 

comprehensively captured and evaluated the literature on these interventions from root to the end 

of 2006), we did not include any reviews on these particular interventions for this time period. 

In addition we retrieved and evaluated references from eligible articles. Hand searching was 

not undertaken, but we reviewed the publication type “letters” (normally excluded from 

reviews); the investigators suggested that, within the content area of cancer genetics, primary 

data information might be published as letters in some journals. Finally, we formally reviewed 

all articles suggested by peer reviewers of the draft evidence report and incorporated those which 

met eligibility criteria. Detailed search strategies are listed in Appendix A. 

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. (Q1, Q2, Q3, Q4) 

 Publication Date: 1990 to June 2008. (Q1, Q3, Q4) 

 2003 to June 2008 (Q1 guidelines/recommendations and Q2) 

Exclusion 

Publications that were editorials, comments, opinions, or abstract only (Q1, Q2, Q3, Q4) 

 22
Eligibility Criteria for Research Q1: 

Population 

Any patient or general populations not selected for known or suspected pre-existing elevated 

risk of breast, ovarian, colorectal, and/or prostate cancer 

Inclusion 

• populations sampled from clinical settings, including population screening programs 

• participants in analytical epidemiological research studies 

Exclusion 

• people with a personal history of breast, ovarian, colorectal, or prostate cancer 

• people at high risk of cancer, as estimated by an existing risk assessment system 

• populations sampled from specialist genetic clinics or cancer family clinics 

• people who have had a genetic test for a mutation related to one of the cancers of 

interest (irrespective of result) 

Intervention 

Inclusion 

Any system designed 

• to use family history information alone, or in combination with other information 

typically and universally available to primary care practitioners (i.e., 

personal/demographic factors, past medical history, clinical observations that do not 

require specialist referral) 

• to stratify people into two or more risk categories OR to provide a numerical point 

estimate of risk of developing breast, ovarian, colorectal, and/or prostate cancer, over 

any time period 

• for application in risk assessment of individual patients 

• in which the model validation is tested on a patient sample different than the one used to 

develop the model 

Exclusion 

• Systems which do not incorporate family history information 

• Systems which include data from specialist investigations which are typically 

unavailable in primary care settings 

Design 

Inclusion 

1. Analytical studies examining disease risk categorization as the ‘exposure’ and cancer 

incidence or proxy as the ‘outcome’ 

• cohort (prospective or historical) 

• case control 

2. Diagnostic studies examining disease risk categorization using the algorithm as the ‘test’ and 

cancer incidence or proxy as the ‘reference’ 

3. Intervention studies examining disease risk classification system as the ‘intervention’ and 

correct prediction of cancer incidence or proxy as the ‘outcome’ 

• randomized controlled trials (cancer risk classification system compared with any other 

system, or no system) 

 23
• non-randomized controlled trials (cancer risk classification system compared with any 

other system, or no system) 

• uncontrolled before-after studies (data on prediction of patients’ cancer risk before and 

after the introduction of a cancer risk classification system) 

Exclusion 

None

Outcome 

Inclusion 

1. Model calibration, expressed as observed versus expected cases 

2. Model discriminatory accuracy, expressed as sensitivity, specificity, predictive value, 

likelihood ratio, concordance statistic, receiver operator characteristics (ROC), area under the 

curve (AUC), or other appropriate summary statistic 

 For the outcomes of 

• incidence of breast, ovarian, colorectal, or prostate cancer 

• breast-, ovarian-, colorectal-, or prostate-specific mortality 

• proxies - incidence of known precancerous states, such as colorectal adenomatous 

polyps 

 Over any defined time period 

Exclusion 

None

Eligibility Criteria for Research Q2 

Population 

Inclusion 

 Reviews where eligibility criteria include AND outcome data are presented separately for: 

General population, primary care patients or participants in population screening programs 

who may or may not have been selected by age and sex criteria but not on the basis of a priori

higher risk, such as: 

• personal history of cancer 

• known precancerous condition 

• known disorder which increases cancer risk 

• known or suspected familial cancer syndrome 

Participants may have had relatives with cancer, but they are not selected specifically on the 

basis of suspected genetic risk 

Exclusion 

Reviews where the eligibility criteria focus specifically on people eligible for, or who have 

had, a genetic test for a cancer-associated mutation (irrespective of result) 

 

Intervention 

Inclusion 

Breast 

• breast self-examination 

• clinical examination 

• screening mammography 

 24
• chemoprevention 

• magnetic resonance imaging breast screening (MRI) 

• referral for genetic counseling +/- genetic testing, where criteria are met 

Colorectal 

• fecal occult blood (FOB) test 

• screening colonoscopy 

• screening sigmoidoscopy 

• chemoprevention 

• referral for genetic counseling +/- genetic testing, where criteria are met 

Ovarian 

• ultrasound screening 

• referral for genetic counseling +/- genetic testing, where criteria are met 

Prostate 

• prostate-specific antigen (PSA) screening 

• digital rectal examination 

• chemoprevention 

• referral for genetic counseling +/- genetic testing, where criteria are met 

General behaviors for all four cancers 

• vitamins, minerals, micronutrient supplementation 

• regular exercise/physical activity 

• high fiber diet 

• increased fruit and vegetable consumption or specific food intake 

• low fat diet 

• smoking cessation 

• reduction in alcohol intake 

• seeking healthcare advice 

• participation in recommended screening/surveillance 

Exclusion 

None 

Comparator/Study Design 

Inclusion 

Systematic reviews of primary studies which seek to identify studies with the following 

designs 

• randomized controlled trials 

• non-randomized controlled trials 

• uncontrolled before-after studies (or non-controlled trials) 

 Comparators: 

• as reported in primary studies 

Exclusion 

Systematic reviews of primary studies which focus solely on the following designs 

• cohort studies 

• case-control studies 

• case series and case reports 

 25
Outcomes 

Inclusion 

• cancer incidence 

• cancer-related mortality 

• all cause mortality 

• incidence of known precancerous conditions 

• complications of diagnosis, complications or side effects of treatment, psychosocial 

sequelae 

Exclusion 

All other outcomes 

Eligibility Criteria for Research Q3 

Population 

Any patient or general populations not specifically selected for known or suspected preexisting elevated risk of breast, ovarian, colorectal, and/or prostate cancer 

Inclusion 

• populations sampled from population or clinical settings, including population screening 

programs 

Exclusion 

• populations selected entirely on the basis of a personal history of breast, ovarian, 

colorectal, or prostate cancer 

• populations selected entirely on the basis of having a high risk of cancer, as estimated by 

an existing risk assessment system or a genetics specialist 

• populations sampled from specialist genetics clinics or cancer family clinics 

• populations selected entirely because they have had a genetic test for a mutation related 

to one of the cancers of interest (irrespective of the result) 

Intervention 

Inclusion 

Systematic provision of personal risk of breast, colorectal, prostate and/or ovarian cancer 

based on family history, alone or combined with individual advice on appropriate risk reduction 

behaviors and/or services 

Exclusion 

• family history taking without provision of personal risk information 

• advice on risk reduction not accompanied by, or based on, family history information 

• provision of general risk information 

• genetic counseling 

Comparator/Study Design 

Inclusion 

 Primary studies of the following study designs: 

• randomized controlled trials 

• non-randomized controlled trials 

• uncontrolled before-after studies (or non-controlled trials) 

 26
Comparators: 

• no comparator group 

• comparator group with no intervention 

• comparator group receiving preventive advice without provision of family history-based 

information 

Exclusion 

• cohort studies 

• case-control studies 

• case series and case reports 

Outcomes 

Inclusion 

• change in target behaviors related to cancer prevention, considered standard advice at the 

time of the primary study 

• uptake of services identified in (Q2) or considered current/standard of care at the time of 

the primary study 

Exclusion 

None 

Eligibility Criteria for Research Q4: 

Population 

Any patient or general populations not specifically selected for known or suspected preexisting elevated risk of breast, ovarian, colorectal, and/or prostate cancer 

Inclusion 

• populations sampled from population or clinical settings, including population screening 

programs 

Exclusion 

• populations selected entirely on the basis of a personal history of breast, ovarian, 

colorectal, or prostate cancer 

• populations selected entirely on the basis of having a high risk of cancer, as estimated by 

an existing risk assessment system or a genetics specialist 

• populations sampled from specialist genetics clinics or cancer family clinics 

• populations selected entirely because they have had a genetic test for a mutation related 

to one of the cancers of interest (irrespective of the result) 

Intervention 

Inclusion 

Systematic collection of family history information and/or the provision of family historybased personal risk of breast, colorectal, prostate, and/or ovarian cancer 

Exclusion 

• advice on risk reduction not based on family history information 

• provision of general risk information 

• genetic counseling 

 27
Comparator/Study Design 

Inclusion 

Primary studies of the following study designs: 

• randomized controlled trials 

• non-randomized controlled trials 

• uncontrolled before-after studies (non-controlled trials) 

Comparators: 

• no comparator group 

• comparator group with no intervention 

• comparator group with intervention not based on family history collection or family 

history-based preventive advice 

Exclusion 

• cohort studies 

• case-control studies 

• case series and case reports 

Outcome 

Inclusion 

• psychological status 

- anxiety/distress 

- cancer worry 

- depression 

- inaccurate risk perception 

- other psychological outcome 

• quality of life 

• social impacts 

- family functioning including dynamics/communication, etc. 

- insurance or employment discrimination 

- other 

Exclusion 

• outcomes not listed above 

Figure 3 illustrates the flow of studies based on the eligibility criteria described.

 28
Figure 3. Flow of studies to final number of eligible studies 

1st Title and Abstract Screening 

n=10,644 

Excluded at 1st title 

and abstract 

n=8,996 

2nd Title and Abstract Screening 

n=1,648 

Excluded at 2nd title 

and abstract 

n=769 

1st Full Text 

Screening 

n=879 838 Excluded from 1st & 2nd Full Text 

Not an eligible publication type ..........................30

Not an eligible population.................................129

Model does not categorize risk or validate...... 175

Not an eligible study design .............................157

Not an eligible intervention or outcome............133

Family history not systematically collected ......214 2nd Full Text 

Screening 

n=503 

Eligible Studies n=41

Question 1 Question 2 Question 3 Question 4 Guidelines 

n=8 n=29 n=3 n=1 n=0 

Study Selection 

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

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

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

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

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

 29
 30

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 screening 

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 developed for use in the SRS (Appendix B). All 

eligible studies from the selection phase (full text screening) were abstracted onto a data form 

according to predetermined criteria. One data extractor 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 investigators responsible for summarizing the different report results sections. 

Quality Assessment and Peer Review 

Quality assessment of studies was undertaken in varying forms. Studies eligible for (Q1) 

were evaluated for potential bias in relation to the model variables and selection bias. For the 

systematic reviews identified for (Q2), a modified version of the Oxman-Guyatt Overview 

Quality Assessment Questionnaire, a validated, 10-item assessment scale was used.82 Studies for 

(Q3 and Q4) were evaluated using the Jadad scale for randomized trials.83 

A draft version of this report was circulated to 14 peer reviewers (see Appendix E). Where 

possible, comments and suggestions were incorporated. 

Summarizing our Findings: Descriptive and Analytic 

Approaches 

A qualitative descriptive approach was used to summarize study characteristics and 

outcomes. Multiple publications on the same study cohort were grouped together and treated as a 

single study with the most current data reported for presentation of summary results. 

Standardized summary tables explaining important study population and population 

characteristics, as well as study results, were created. Meta-analysis was not undertaken for 

eligible studies for (Q1, Q3, or Q4) as the clinical heterogeneity between studies was 

considerable. 
Chapter 3. Results 

Our comprehensive search yielded 10,644 unique citations; from these 9,765 were excluded 

as they were not an English language publication, not on the cancers of interest, or on topic for 

any of the four research questions (Figure 3). The remaining 879 citations were screened at full 

text and of these a total of 12 primary studies and 29 systematic reviews were eligible for 

inclusion in this review. 

Research Q1: Which Risk Stratification Algorithms or 

Guidelines Delineate Risk Accurately, and in a Clinically 

Meaningful Way? 

General Approach 

We reviewed published studies which examined the ability of models (or algorithms, or 

guidelines) which used family history information to accurately predict individual risk of breast, 

ovarian, colorectal, or prostate cancer. To be eligible, the model had to include systematic 

collection of specified family history information, either alone or with other personal or clinical 

information which would be available for all patients and routinely available to a primary care 

practitioner. We examined the performance of models in relation to populations not selected for 

known or suspected high risk of cancer. 

Model performance was assessed by predictive accuracy, in terms of calibration and 

discrimination. “Calibration” is a model’s ability to correctly predict the number of observed 

events (incidence of cancer) in a population and is generally evaluated by its goodness-of-fit to 

observed events. The ratio of observed to expected cases provides an overall epidemiological 

assessment of how well a model might perform for a defined population. 

“Discrimination” is the assessment of how well a model separates out individuals who will 

go on to develop different outcomes. Discriminatory accuracy for dichotomous outcomes (e.g., 

disease/no disease) is best examined through metrics such as sensitivity and specificity, 

predictive value, likelihood ratio, and the area under the receiver operator characteristic (ROC) 

curve (or area under the curve (AUC)). The AUC is also referred to as the c-statistic and is 

defined in the unit square with a range of 0 to 1.0. Since chance alone will follow a perfect 

diagonal from (0,0) to (1,1), the subsequent AUC will be 0.5 (no apparent discrimination), 

whereas an AUC of 1.0 indicates perfect discriminatory accuracy. 

Discriminatory accuracy is a more relevant evaluation than calibration from the point of view 

of clinical practice, as it directly indicates how well the model predicts an individual patient’s 

likelihood of developing cancer within a defined time scale. A model that is well calibrated at a 

population level may not necessarily be highly discriminating when used for individual 

prediction. 

Studies Reviewed 

Eight evaluation studies were retained for data abstraction after full text review.7-14 All 

except one focused on breast cancer risk assessment. The individual breast cancer models were 

 31
all conceptually related: the “original” Gail model,15 the modified Gail model,84 the modified 

Gail model for African American populations,10 the modified Gail model for Italian 

populations,11,12 and the model developed from the Contraceptive and Reproductive Experiences 

(CARE) study.7

 The exception was Harvard Cancer Risk Index (HCRI),16 which was developed 

for calculating the risk of a several cancers, including breast, ovary, colon, and prostate. An 

eligible validation14 of the HCRI was published only for colon cancer. 

The details of the models are summarized in Table 4. All of the models examined used a set 

of predetermined input variables in addition to family history as the basis for risk assessment. 

These variables included a range of personal demographic and disease-specific risk factors such 

as age, ethnicity, reproductive factors, diet, history of clinical investigations (e.g., breast 

biopsies, colonoscopies), and other risk factors such as body mass index, and alcohol 

consumption. 

Outcomes 

The details of evaluations of the models are summarized in Table 5. All evaluations were 

performed as secondary analyses of data derived from observational studies or trials. The sample 

sizes for the evaluations ranged from 1,450 to 147,916, covering a wide age range of 

participants. Six of the evaluations7-10,13,14 were conducted in U.S. populations: the Nurses’ 

Health Study (NHS)14,85,86 (4 studies), the Women’s Health Initiative (WHI)7,87 (2 studies), the 

Black Women’s Health Study,88 and the Health Professionals Follow-Up Study (HPFS).87 The 

remaining two evaluations11,12 were conducted in Italian populations. Followup periods in the 

validation cohorts ranged from 5 to 10 years. 

Gail Model 

The first published version of the ‘Gail Score’15 used information on a woman’s age at 

menarche, her age at the time of the birth of her first child, the number of her first degree 

relatives who had had breast cancer, and the number of previous breast biopsies that she had 

undergone. It was designed for women with no personal history of breast cancer who were being 

followed by annual screening mammography. It estimates the absolute probability of developing 

invasive or in situ breast cancer over a defined age interval. The model uses estimates of baseline 

hazard and attributable risk derived from the Breast Cancer Detection Demonstration Project 

(BCDDP).89 The authors indicated that its primary application would be to “determine eligibility 

for entry to breast cancer prevention trials, where an important determinant of sample size is the 

absolute risk of breast cancer” in the study population.15

We identified a single study8

 which evaluated the original Gail model,15 a secondary analysis 

of data from the NHS.85,86 The ratio of expected to observed breast cancer cases was 1.33 (95 

percent CI 1.28-1.39), which was a significant overestimation. Only modest discriminatory 

accuracy was demonstrated (Pearson correlation coefficient 0.67). 

Modified Gail Model 

The modified Gail model incorporated revisions to improve its validity and applicability to 

the North American population.84 The key revisions were a focus on the absolute risk of invasive 

breast cancer only (i.e., in situ cancer was excluded): the inclusion of a diagnosis of atypical 

 32
hyperplasia on biopsy as an additional risk factor; and the substitution of age-specific invasive 

breast cancer rates from the Surveillance, Epidemiology, and End Results (SEER) Program of 

the National Cancer Institute (NCI) for the BCDDP-based data used in the original model. 

 We identified five studies which evaluated the performance of the modified version of the 

Gail model, either in its originally published form, or adjusted to take account of different 

underlying breast cancer incidence patterns in different populations (African American,10

Italian11,12). The ratios of expected to observed invasive cancer cases ranged from 0.79 to 0.96, 

mostly not statistically significantly different from unity. Validations, performed in a 

predominantly white U.S. population9

 and two Italian populations,11,12 suggested reasonably 

good calibration, but poorer performance in “more diverse”13 and African American10 U.S. 

populations. These studies all suggested that the standard and modified versions all had very 

modest discriminatory accuracy (concordance statistic 0.58-0.59). 

CARE Model 

The CARE Model7

 was developed as an African American adaptation of the Gail model, 

using data from the Women’s Contraceptive and Reproductive Experiences (CARE) Study,90 the 

SEER program, and National Center for Health Statistics. It is a simpler model, in that two 

variables in the modified Gail model were removed and one was dichotomized. 

We identified one study that validated this model, in a subset of African American women in 

the WHI. The model showed good calibration, with an expected observed ratio of cases not 

statistically significantly differently from unity. The discriminatory accuracy, expressed as AUC, 

was 0.555, which suggests only very modest predictive ability at best. 

The authors compared the CARE Model with the MGM in classifying eligibility for a 

chemoprevention trial, and found that it doubled the proportion of women who met inclusion 

criteria (30.3 percent compared with 14.5 percent). 

Harvard Cancer Risk Index 

The HCRI was developed as a tool to assist clinicians in counseling patients about cancer 

risk reduction.16 It addressed prediction of the most common cancers in American men and 

women (prostate, breast, lung, colon, bladder, endometrium, non-Hodgkin’s lymphoma, ovary, 

kidney, leukemia, cervix, pancreas, skin melanoma, and stomach). The tool was developed using 

a consensus-based process in which available evidence was used to assign points for different 

levels of defined risk factors. Risk was stratified into a seven point categorical scale, set relative 

to the average U.S. population risk for each cancer. Several risk factors contributed to the score 

for each cancer, family history being included in all except leukemia and cervical cancer. 

We identified one validation study,87 in which the HCRI’s predictive validity for colon 

cancer was assessed in two cohorts, the NHS (women) and the HPFS (men). Results pertaining 

to ovarian cancer were also reported in this publication, but family history items were lacking, 

therefore these data were excluded from the current review. In addition to family history, eight 

variables for men and eleven for women were included in the HCRI for colon cancer. 

The overall ratios of observed and expected cases were not reported. For women, the ratios 

by initial risk stratum ranged from 0.58 to 1.79, and for men 0.75 to 2.35. A better fit was 

observed for women than men. The AUC was 0.67 for women and 0.71 for men, suggesting 

moderately good discriminatory accuracy. 

 33
Conclusion 

There were essentially two families of tools on which relevant performance data were 

available, those based on the Gail model, and the HCRI. None of the identified studies evaluated 

the performance of a predictive tool or algorithm, designed for use in populations not already 

pre-selected for higher risk, and using family history information alone. No validation studies of 

tools designed for risk prediction for ovarian or prostate cancer were found. 

 Most, but not all models demonstrated good calibration for the populations for which they 

were developed. However, none of the models identified demonstrated more than moderate 

ability to correctly discriminate risk at an individual level. The highest concordance presented 

was 0.71: this is equivalent to the correct classification of future disease (present or absent) in 71 

percent of individuals, and incorrect classification of 29 percent. 

Research Q2: For Which Behaviors and Clinical Preventive 

Services is There Evidence of Benefit in Terms of Actual 

Reduction of Disease Risk, and What Harms, if any, Have 

Been Identified? 

General Approach 

 For the purposes of this review, we included published quantitative and qualitative reviews of 

the effectiveness of personal behavioral/lifestyle and clinical interventions that are commonly 

recommended as part of cancer risk reduction strategies in primary care settings. The list of 

interventions of interest was developed by the study team in consultation with the partners and 

the members, and was incorporated into the eligibility criteria for the review. Table 6 lists the 

interventions of interest. 

 Where multiple reviews addressing the same intervention were identified, they were 

scrutinized to determine the degree of overlap, as well as for quality. We selected the most recent 

and/or most comprehensive review for reporting, bearing in mind any differences in quality.17 

Studies Reviewed 

 Twenty-nine systematic reviews fulfilled eligibility criteria after full text review. These 

eligible reviews addressed evidence for four chemoprevention interventions (antioxidant 

supplementation, calcium supplementation, non-steroidal anti-inflammatory drugs (NSAIDS), in 

the form of aspirin, but not COX-2 inhibitors and statins) and five screening interventions (breast 

self-examination (BSE), screening mammography, fecal occult blood testing (FOBT), flexible 

sigmoidoscopy (FS), and prostate specific antigen (PSA), for three cancers (breast, colorectal, 

and prostate). 

No reviews were identified which examined evidence for magnetic resonance imaging in 

breast screening, ultrasound ovarian screening, colonoscopy as a stand-alone screening 

intervention, regular exercise, dietary interventions other than supplements (reviewed under 

chemoprevention), reduction in alcohol consumption, smoking cessation, seeking health care 

advice or referral for genetic counseling and/or genetic testing. As mentioned in chapter 2, we 

 34
did not search for reviews for food, nutrition or physical activity interventions before 2006 as 

these were well evaluated in the World Cancer Research Fund/ American Institute for Cancer 

Research Second Expert Report.81

 Of the eligible studies, data were extracted from the 10 reviews which represented the most 

comprehensive, up-to-date, and high quality evidence.18-27 Twelve additional reviews reported 

overlapping data28-39 but these data were not extracted. Five reviews40-44 did not identify primary 

intervention studies despite being designed to do so; and two reviews45,46 identified apparently 

relevant intervention studies but did not report usable data. The studies, which were not reported, 

on are listed in Table 1 in Appendix C. 

 The findings of the reviews which were included and reported are presented in Tables 7, 8, 

and 9. Some reviews addressed evidence related to prevention of more than one cancer type; in 

this situation, the results are presented separately by cancer type. 

Breast Cancer 

 Five reviews on breast cancer prevention18-22 are presented in Table 7 which synthesizes 

evidence in relation to chemoprevention (antioxidants and statins), screening (BSE), and 

screening mammography. 

Chemoprevention. ‘Chemoprevention’ refers to the use of chemical compounds to arrest or 

reverse the earliest stages of carcinogenesis or development of pre-cancerous lesions. We apply 

it very broadly in this review to include the use of both recognized pharmaceutical agents (drugs) 

and supplements of naturally occurring elements and compounds administered in doses above 

those naturally encountered in typical diets, and/or administered in tablets or capsule. 

Antioxidants. Antioxidants are molecules which inhibit or prevent damage to cells caused by 

oxidizing agents such as oxygen free radicals. It is suggested that such damage (oxidative stress) 

is an important early step in the development of many diseases, including cancer. It is 

hypothesized that antioxidant compounds could act as cancer prevention agents by preventing or 

inhibiting DNA damage, the earliest stage of carcinogenesis. Many observational 

epidemiological studies have found an inverse relationship between consumption of foods with 

high antioxidant content, such as fruits and vegetables, and incidence of cancer.71-73 

 Antioxidants are a diverse group of compounds and different reviews have assessed them 

collectively and individually. Among the many antioxidants associated with food, the most 

commonly studied are vitamins (A, C, and E), their precursor molecules (e.g., alpha-tocopherol 

and ß-carotene), and minerals (e.g., selenium and zinc). 

 We report the findings of two reviews that examined antioxidants and breast cancer 

incidence. The first review18 evaluated supplements which contained any combination of ßcarotene, vitamin C, vitamin E, selenium, zinc, and other antioxidants, and the second review19

focused on vitamin E in any combination. Both of these reviews also evaluated outcomes related 

to colorectal and prostate cancer, the results for which are presented in the relevant sections 

below. 

 The first review18 included only placebo-controlled trials where antioxidants were given as 

supplements where the ingredients were fully disclosed, and which had followed up participants 

for at least one year. Their breast cancer analysis was based on 1,753 cancers in a total of 88,392 

participants enrolled in the primary trials. No evidence was found of a protective effect of any 

combination of antioxidants against breast cancer (RR 1.00, 95 percent CI 0.90-1.09). 

 35
 The second review19 examined vitamin E alone or in any combination. It included 

randomized controlled trials (RCTs) where vitamin E, in tablet or capsule form with or without 

other components, was evaluated against a control group receiving placebo or no intervention. 

They assessed the methodological quality of all included trials as high. They identified three 

trials, involving 62,158 participants, in which breast cancer incidence was reported as an 

outcome. They concluded that there was no evidence of a protective effect of vitamin E 

supplementation against breast cancer (RR 0.99, 95 percent CI 0.90-1.10). 

Statins. Statins (hepatic 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase 

inhibitors) are a class of lipid-lowering drugs that are widely prescribed for people at risk of 

cardiovascular disease. Interest in whether use of statins is associated with cancer risk was 

prompted by safety monitoring findings from cardiovascular prevention trials.91 Some studies 

suggest that they may also have a protective effect against cancer,92-98 while others suggest the 

opposite.99-101 Setoguchi et al., (2007)102 observed that longterm statin users tend to be healthier 

overall than non-users, and suggested that this might explain the positive associations. 

 Table 7 summarizes findings from the most comprehensive recent review20 that examined the 

evidence for statins in reducing the risk of a range of cancers, including breast, colorectal, and 

prostate (data for the latter two presented below). This review focused on placebo-controlled 

trials of any statin involving any population except participants being treated for particular high 

risk indications (e.g., familial hypercholesterolemia). The overall analysis indicated that statins 

appear to confer neither a protective nor a harmful effect on breast cancer incidence (RR 1.01, 95 

percent CI 0.79-1.30). The findings were unaltered in sub-group analyses comparing lipophilic 

and lipophobic statins, and low, medium, and high potency statins. 

 Screening. Breast self-examination (BSE). It has been believed for many years that the 

practice of regular BSE allows women to detect breast tumors at an early stage, and thus to seek 

early treatment and improve their chances of cure. It is also considered inexpensive, noninvasive, and can be done in private.103,104 Observational evidence suggests that women 

diagnosed with breast cancer who have practiced BSE are more likely to have found the tumor 

themselves, to have smaller tumors (on average) at the time of diagnosis, and to have benefited 

from longer survival.105 Critics of such analyses point to the possibility of lead-time bias, and the 

need to examine mortality rates as a more valid method of examining outcomes. 

We report the findings of one systematic review21 which identified primary reports of three 

large randomized controlled trials, in two of which the intervention was teaching BSE in general 

populations and, in the third, clinical breast examination followed by teaching BSE. The latter 

was discontinued after the first screening round because of poor compliance, so data were 

available for only two trials. A total of 587 breast cancer deaths were observed in a total group of 

participants of 388,535 across the two trials. The relative risk of breast cancer mortality was 1.05 

(95 percent CI 0.90-1.14). There was no statistically significant effect on the total number of 

cancers identified. There was a non-significant trend towards the detection of smaller tumors 

(carcinoma in situ RR 1.32, 95 percent CI 0.82-2.14, tumors ≤2cm RR 1.13, 95 percent CI 0.99-

1.28). There was a statistically significant increase in total number of breast biopsies and 

biopsies with benign pathology (RR 1.53, 95 percent CI 1.47-1.60, and 1.88, 95 percent CI 1.77-

1.99, respectively). These two large, longterm, population-based trials provide robust evidence 

that teaching women to perform regular BSE does not translate into a lower mortality rate from 

breast cancer, and is associated with a higher rate of invasive investigation. 

Screening mammography. Mammography as an investigative technology for suspected 

breast pathology has been available for several decades, and has been gradually introduced, and 

 36
evaluated, as a potential screening strategy for breast cancer. The rationale for mammography is 

that screening may detect tumors at a stage before they are palpable through self- or clinical 

examination, and that these smaller tumors are less likely to have become locally invasive or 

metastasized. Screening mammography aims to detect early malignant tumors and, if effective, 

would be expected to reduce breast cancer, and overall, mortality, but not breast cancer 

incidence.

 Screening mammography has been the focus of a relatively large number of controlled trials 

in a range of countries, and between 1992 and 2002, 22 systematic reviews of screening 

mammography were published.106-127 This level of scrutiny reflects ongoing controversies about 

the quality of the primary trials, and the possibility for harm which some experts consider 

inadequately examined and appreciated.106,128

 We summarize the findings of the most recent comprehensive review22 that attempts to 

address these issues through analyzing the outcome of all-cause mortality as well as breast 

cancer mortality, by sensitivity analyses according to adequacy of allocation procedures in 

primary trials, and by assessing rates of different treatment modalities in screened and control 

groups. The data are presented in Table 7. 

 This review examined data from 10 completed RCTs involving about half a million women. 

Of these, the reviewers considered only three trials to have been adequately randomized, and 

conducted a meta-analysis for these three separately. The trials covered a wide range of age 

groups, from 39 to 74 years, although most studies focused on women within the 40-59 age 

group. The reported screening intervals ranged from annual to about 2 years. In some studies, 

screening was accompanied by clinical breast examination, physical examination, or 

encouragement to perform monthly BSE. In most trials, the control intervention was usual care. 

 The overall analysis suggested that screening mammography is associated with reduced 

breast cancer mortality at 13 years (RR 0.80, 95 percent CI 0.73-0.88), but the association is 

more marked for the trials considered ‘sub-optimally randomized’ (RR 0.75, 95 percent CI 0.67-

0.83) than for ‘adequately randomized trials (RR 0.93, 95 percent CI 0.80-1.09). When all cause 

mortality outcomes are considered (which would incorporate serious harms caused by overtreatment), the pooled estimates are very similar for trials considered ‘adequately randomized’ 

(RR 1.00, 95 percent CI 0.96-1.04) and ‘sub-optimally randomized’ (RR 0.99, 95 percent CI 

0.97-1.01). 

Colorectal Cancer 

 Six reviews are presented in Table 8 which synthesizes evidence in relation to colorectal 

cancer (CRC) prevention, four relating to chemoprevention (antioxidants, NSAIDS, and statins) 

and two relating to screening (FOBT and FS). 

Chemoprevention. The rationale for chemoprevention is described in previous section on 

breast cancer. 

Antioxidants. The background to antioxidants is described in previous section on breast 

cancer. 

We report the findings of two reviews which examined antioxidants and CRC incidence. The 

first18 evaluated supplements which contained any combination of β-carotene, vitamin C, vitamin 

E, selenium, zinc, and other antioxidants, and the second19 focused on vitamin E in any 

combination. Further details of these reviews are included in the section on breast cancer. 

 37
The first review18 conducted an analysis of 1,523 cancers in a total of 178,086 participants 

enrolled in the primary trials. No evidence was found of a protective effect of any combination 

of antioxidants against CRC incidence (RR 1.00, 95 percent CI 0.90-1.10). 

The second review19 identified four trials focusing on CRC. For vitamin E given in any 

combination (91,099 total participants), they found no evidence of an association with CRC 

incidence (RR 0.95, 95 percent CI 0.81-1.12). Similarly, there was no association when they 

examined data from two trials (24,114 participants) which evaluated vitamin E alone (RR 1.05, 

95 percent CI 0.79-1.39). 

Together, these reviews provide no evidence of a positive or negative association between 

antioxidant or vitamin E supplementation, and CRC risk. 

NSAIDS. NSAIDs are a group of compounds which have an anti-inflammatory effect 

generally due to their action as non-selective inhibitors of the enzyme cyclooxygenase. Their 

potential protective effect against CRC has been observed in a number of case-control and cohort 

studies;129-136 there is also evidence of their effectiveness in preventing recurrence of colorectal 

adenomatous polyps.137,138 

We identified two systematic reviews that examined one specific NSAID only, ASA, in CRC 

prevention. We report the findings of the single review that conducted a formal meta-analysis.23

This review identified two primary studies that evaluated CRC incidence (one at 5 years, the 

other at 10 years) in individuals at average risk (including no personal history of adenomas); one 

of these trials also reported CRC mortality and the other examined the incidence of colorectal 

adenomas. The intervention in both of these studies was ASA at doses recommended for 

cardiovascular protection (i.e., 325 mg every other day or 100 mg/day). Apparently no primary 

studies of standard doses (i.e., ≥325 mg/day) have examined cancer outcomes in average risk 

individuals. The combined number of participants in these two studies was 61,947. No 

statistically significant association was identified between low dose ASA and CRC incidence 

(pooled RR 1.02, 95 percent CI 0.84-1.25), CRC mortality (RR not reported) or adenoma 

incidence at 5 years (RR 0.86, 95 percent CI 0.68-1.10). These results provide no direct 

information on the effectiveness of either higher doses of ASA, or other NSAIDS, on colorectal 

neoplasia. 

Statins. The background to statins is described in previous section on breast cancer. A 

comprehensive systematic review20 examined the evidence for statins in reducing the risk of 

CRC as well as breast (reported above) and prostate cancer (reported below). Data was 

synthesized for nine trials which examined CRC incidence, and one which evaluated CRC 

mortality, as outcomes. The overall analysis indicated that statins appeared to confer neither a 

protective nor a harmful effect on CRC incidence (pooled RR 1.02, 95 percent CI 0.89-1.16) or 

mortality (RR 0.33, 95 percent CI 0.07-1.63). The findings were unaltered in sub-group analyses 

comparing lipophilic and lipophobic statins, and low, medium and high potency statins. 

Screening. Evidence from a wide range of studies139-141 suggests that CRC results from 

complex interactions between genetic and environmental factors, and that most cancers evolve 

from small adenomas over a period of years.140,141 The possibility of preventing CRC cases and 

deaths by early intervention to remove colorectal adenomas and/or early stage cancers has led to 

a large number of studies of a range of screening strategies, specifically involving FOBT, 

colonoscopy and sigmoidoscopy.142 There is no consensus on the optimum combination of these 

modalities, or on the ideal screening interval. 

FOBT. The most widely used approach to FOBT is the stool guaiac test, in which the 

presence of heme (from haemoglobin) is indicated by a color change when hydrogen peroxide is 

 38
added. This is a result of the oxidation of guaiac by the peroxide. A newer class of occult blood 

tests (immunochemical) rely on the detection of globin rather than heme, and it is suggested that 

these are more sensitive and specific than guaiac tests.143

A number of reviews examined FOBT-based screening strategies, of which one is reported 

here.24 This review examined RCTs only of FOBT (guaiac or immunochemical) in which at least 

two rounds of screening were compared with no-screening controls. This review analyzed data 

from four trials involving a total of 329,642 participants. A statistically significant effect of 

screening on CRC mortality was observed (pooled RR 0.84, 95 percent CI 0.78-0.90), which 

remained when the three trials with biennial screening were examined separately. No effect on 

all-cause mortality was observed (pooled RR 1.00, 95 percent CI 0.99-1.01), but a statistically 

borderline association with non-CRC mortality was noted (pooled RR 1.01, 95 percent CI 1.00-

1.03). The interpretation of these combined results is difficult. It is argued that effective CRC 

screening would have little impact on all-cause mortality because CRC makes only a small 

contribution to overall mortality in these populations (and screening trials are therefore 

inadequately powered to detect such an effect). There is also an argument that biased attribution 

of cause of death between screened and control groups can lead to an overestimate of the true 

effect of screening on mortality, therefore an assessment of all-cause mortality would provide a 

more valid assessment of effectiveness.144 

We do not present data from a further systematic review36 which focused on guaiac-based 

biennial FOBT screening alone; it included a non-randomized controlled trial excluded from the 

review reported above24 and excluded one of the latter’s included trials. The pooled results are 

consistent with those reported above and in Table 8. 

Flexible sigmoidoscopy. Flexible sigmoidoscopy (FS) is an endocopic technique which 

allows visualization of the colon and rectum distal to the splenic flexure. FS has a very low 

complication rate.145,146 The majority of CRCs arise in the distal colon, thus are theoretically 

detectable with FS, and detection of distal adenomas is an indication for full colonoscopy.147 It is 

suggested that a combined strategy such as this can detect about 80 percent of CRC cases in men 

and about 50 percent of those in women, without recourse to more invasive colonoscopy as a 

primary screening modality.148-150 

We identified one review25 which examined the evidence for FS in CRC screening. One 

RCT was identified which compared FS in addition to FOBT against FOBT only (positive 

screens being followed up by colonoscopy). This review also considered FOBT alone as a 

screening strategy, but the data were not extracted as they are similar to the review reported 

above.24 This trial involved 10,978 participants and showed no statistically significant effect of 

the combined FS plus FOBT strategy on CRC mortality or incidence (RR 0.78, 95 percent CI 

0.36-1.73 and 1.37, 95 percent CI 0.88-2.15, respectively). No formal intervention studies 

comparing FS alone with either no screening, or FOBT only, have been identified. 

Prostate Cancer 

Five reviews18-20,26,27 are presented in Table 9 which synthesizes evidence in relation to 

prostate cancer prevention, four relating to chemoprevention (antioxidants, calcium, and statins) 

and one relating to screening (PSA, digital rectal examination (DRE), and transurethral 

ultrasound (TRUS) biopsy). 

Chemoprevention. The rationale for chemoprevention is described in previous section on 

breast cancer. 

 39
Antioxidants. The background to antioxidants is described in previous section on breast 

cancer. 

We report the findings of two reviews which examined antioxidants and prostate cancer 

incidence. The first18 evaluated supplements which contained any combination of β-carotene, 

vitamin C, vitamin E, selenium, zinc, and other antioxidants, and the second19 focused on 

vitamin E in any combination. Further details of these reviews are included in the section on 

breast cancer. 

The first review18 conducted an analysis of 2,143 new cancers in a total of 55,709 

participants enrolled in the primary trials. Overall, the pooled analysis indicated a small, nonstatistically significant decrease in prostate cancer incidence when all antioxidants were 

considered together (pooled RR 0.87, 95 percent CI 0.74-1.02). Noting high heterogeneity, a 

sensitivity analysis suggested that vitamin E in particular was associated with a reduced risk 

(pooled RR 0.82, 95 percent CI 0.67-0.99), based on three trials. The authors of this review also 

noted that “one trial report a decreased incidence of prostate cancer with selenium,” although 

they did not provide relative risk data. Reporting on the same trial,151 another review26 (included 

below) estimated that, for a daily dose of 200μg of selenium (compared with placebo), the 

relative risk for prostate cancer incidence was 0.37 (95 percent CI 0.20-0.70). 

The second review19 evaluated the effect of vitamin E alone or in combination, and 

performed a meta-analysis on three primary trials. For vitamin E given in any combination 

(71,759 total participants), the pooled estimate for effect on prostate cancer incidence also 

indicated slightly reduced risk (pooled RR 0.85, 95 percent CI 0.74-0.96). Two trials examined 

vitamin E alone, with no evidence of an association (pooled RR 0.86, 95 percent CI 0.70, 1.06). 

Similarly, there was no association when they examined data from two trials (24,114 

participants) which evaluated vitamin E alone (RR 1.05, 95 percent CI 0.79-1.39). 

Together, these reviews suggest no evidence of an effect of combined antioxidant 

supplementation on prostate cancer risk, but potentially a small protective effect of vitamin E 

supplementation. 

Calcium. The association between calcium intake and prostate cancer risk has been examined 

both from risk increasing and risk reducing perspectives. Observational studies have indicated a 

positive association between calcium intake and prostate cancer, the suggested mechanism being 

that calcium lowers circulating vitamin D concentrations, and this in turn alters prostate cell 

proliferation.152-155 In contrast, some studies have suggested that dietary calcium decreases 

prostate cancer risk.156-162

We identified one review which analyzed intervention study data relating to calcium and 

prostate cancer risk.26 This review identified a single primary trial of calcium supplementation, 

designed to evaluate calcium as a protective agent against recurrence of colorectal adenomas, 

where prostate cancer incidence was evaluated as a secondary outcome.47 Supplements 

equivalent to 1,200 mg elemental calcium daily were given for 4 years and participants followed 

up for another 7 years. This trial observed 70 prostate cancers in 672 men with an RR for 

prostate cancer incidence of 0.83 (95 percent CI 0.52-1.32). Detailed review of the results 

suggested a statistically significantly lower incidence of prostate cancer in the supplement group 

until 2 years after supplementation was discontinued (RR 0.52, 95 percent CI 0.28-0.98), at 

which point the risk in both groups converged. It is suggested that calcium may have a slight 

protective effect, which is maintained only by ongoing supplementation. This finding from a 

single trial is insufficient to recommend calcium supplementation specifically for the purpose of 

 40
prostate cancer prevention, particularly given the contradictory findings of previous 

observational studies. 

Statins. The background to statins is described above in previous section on breast cancer. 

We present data from the comprehensive systematic review described in previous sections,20

which examined the effectiveness of statins in reducing the risk of several cancers. Four trials 

examined prostate cancer incidence, and one evaluated prostate cancer mortality. The overall 

analysis indicated that statins appeared to neither increase nor decrease risk of prostate cancer 

incidence or mortality (pooled RR 1.00, 95 percent CI 0.85-1.17 and RR 0.99, 95 percent CI 

0.14-7.01 respectively). No data were presented with regard to lipophilic versus lipophobic, or 

low, medium and high potency statins. 

Screening. Prostate-specific antigen-based strategies (PSA). Strategies for screening for 

early prostate cancer have revolved around the combined use of PSA with or without DRE of the 

prostate, followed by needle biopsy guided transrectal ultrasound (TRUS). Digital rectal 

examination has limited sensitivity because it is not possible to palpate the entire prostate gland, 

while PSA testing produces high rates of false positive and false negative results.163 In addition, 

although reductions in prostate cancer mortality have been demonstrated with early 

treatment,164,165 there remains considerable concern about lead and length time bias, the 

overtreatment of men who have indolent disease (tumors which were never destined to be 

fatal),166 and harms associated with treatment.167-170 

We identified a single review27 which examined the effectiveness of population-based 

screening in preventing death from prostate cancer. This study identified two trials of screening 

strategies that combined PSA testing, DRE and TRUS biopsy for diagnostic investigation, one of 

which used an annual, the other a 3 times yearly, screening cycle. The total number of 

participants randomized was 55,512, and 345 prostate cancer deaths were observed over 

followup periods of at least 11 years. No statistically significant impact of screening on prostate 

cancer mortality was found (pooled RR 1.01, 95 percent CI 0.80-1.29). No data were presented 

in relation to all-cause mortality. The authors of the review considered that both trials had a high 

risk of bias. The overall findings indicate that PSA-based screening cannot be considered to be 

an effective secondary prevention intervention in prostate cancer. 

Quality Assessment of Studies 

Standardized quality assessment checklists using a modified scoring version of the Oxman 

and Guyatt criteria82 were employed for all systematic reviews. The range of scores was 11-17 

out of a possible 18. The major area of weakness was failure to describe adequate control of bias 

in the selection of studies for review.18-20,22,23,27 Other issues encountered in a minority of 

reviews were incomplete description of search methods,23,27 and failure to describe criteria for 

assessing the validity of primary studies,20,25,26 or to cite the validity assessments of included 

studies.20,26 

Overall, the potential for bias in these reviews appears quite low. It is impossible to say 

whether failing to adequately describe search strategies, methods for controlling selection bias, 

or assessing validity of studies reflects methodological shortcomings or only failure to report 

these in published articles. 

 41
Conclusion 

We were able to locate relevant systematic reviews relating to prevention, in average risk 

populations, of breast, colorectal, and prostate cancers, but not ovarian cancer. For all three 

cancers, the core primary prevention strategy for which reviews could be identified was 

chemoprevention. For breast and CRC, no evidence of an effect on cancer incidence of 

antioxidant supplements in general, vitamin E supplements in particular, or statins. For CRC, 

data on NSAIDS were available, with no evidence of an effect on cancer incidence. For prostate 

cancer, equivocal evidence was found of a possible protective effect of vitamin E supplements, 

selenium, and calcium supplements. 

Screening strategies were also examined. For breast cancer, a review of three large 

population-based trials, confirm that BSE is not an effective strategy for reducing mortality from 

breast cancer and may increase morbidity through unnecessary investigations. Screening 

mammography has been evaluated in a large number of meta-analyses, which indicate that 

population-based screening appears to consistently reduce breast cancer mortality by about 15 

percent, although there is still an open debate on whether all-cause mortality is a more valid 

measure of benefit of this intervention. There is concern that screening leads to higher rates of 

investigation and over treatment which undermine overall benefits. The analyses are based on 

studies with participants with a wide range of age ranges, which makes it difficult to discern the 

extent to which the profile of benefits and risks change according to target age. Both the 

technical performance of the screening test, in terms of sensitivity and specificity, and the prior 

risk of breast cancer, vary according to age, therefore the predictive value is not constant across 

all age groups. Also, the level of any risks associated with overtreatment will depend on local 

protocols for diagnostic investigation and treatment. 

For CRC, FOBT-based screening strategies (which generally include diagnostic investigation 

using colonoscopy) appear to be associated with a decrease in CRC mortality, and the limited 

evidence available suggests that adding FS does not improve their effectiveness. As with breast 

screening, it is argued that all-cause mortality may provide a more valid assessment of screening 

effectiveness; however, since the proportion of overall mortality attributable to CRC is low, 

screening studies are generally underpowered to detect an effect. 

With respect to prostate cancer, we found no evidence that PSA-based screening strategies 

are effective in reducing mortality. 

Research Q3: For Those Interventions Identified as Being 

Based on Reasonable Evidence, What is the Evidence That 

Providing Information on Risk Status Results in Behavior 

Change or Increased Uptake of Services on the Part of 

Individual Patients? 

General Approach 

We reviewed published intervention studies (RCTs, controlled trials, and before-after 

studies) that examined the impact of systematic collection of family history information on one 

or more risk-reduction behaviors for breast, ovarian, colorectal, or prostate cancer. To be 

 42
included, the intervention had to comprise systematic collection of individual family history 

information, and also communication of personal risk of one or more of the cancers of interest. 

This could be accompanied by individualized advice on specific risk reduction behaviors, 

although this was not necessary for a study to be included. The target behaviors of interest were 

both personal/lifestyle, and adherence to recommended clinical preventive interventions such as 

screening; the interventions were those considered standard of care when the primary study was 

conducted. 

Studies Reviewed 

Three studies48-50 were retained for data abstraction after full text review. These studies all 

focused on breast cancer risk assessment and mammography screening, with or without other 

behaviors, as the target intervention (Table 10). Two of the studies were RCTs49,50 and the 

other48 was an uncontrolled before-after study. 

The sample sizes ranged from 188 to 2,076, and participants were recruited from a health 

maintenance organization (HMO),49 community pharmacies/health promotion events,48 and as 

first degree relatives (1DR) of breast cancer patients.50 Family history information was captured 

by computer-assisted telephone interview,50 postal questionnaire,49 and interviewer-administered 

questionnaire.48 In all three studies, information relating to personal medical history was 

collected as well as family history information. The 1DR and community pharmacy studies48,50

specified use of the Gail model for risk calculation, which requires information on the number of 

1DRs with breast cancer; the HMO study49 used a risk stratification algorithm developed inhouse, which included information on first and second degree relatives with breast cancer.171

The HMO study49 had four groups, with two levels of collection of family history 

information (collected or not collected) and three levels of risk information included in screening 

invitation letters (no reinforcement, general risk messages, personalized risk messages) in the 

following combinations: 

• no collection of individual risk information plus generic invitation for mammography 

• no collection of individual risk information plus general risk messages embedded in 

invitation for mammography 

• collection of individual risk information plus general risk messages embedded in 

invitation for mammography 

• collection of individual risk information plus personalized risk messages embedded in 

invitation for mammography. 

Data on the outcome of mammography uptake by 12 months were captured using the HMO’s 

databases. 

The 1DR study50 had two groups, both of which had individual family history information 

collected, and personalized information on risk of breast cancer fed back. The two groups had 

different levels of reinforcement of the importance of, and reminders to undertake, the target 

behavior of screening mammography. Data on the outcome of uptake of mammography was 

assessed by self-report at 12 months, captured by mail or telephone survey. 

The community pharmacy study48 had one group of participants, all of whom had individual 

family history information collected and personalized information on risk of breast cancer fed 

back, along with reminders of recommended screening behaviors. Data on the outcomes of selfreported uptake of mammography, and adherence to BSE and clinical breast examination (CBE) 

recommendations, was captured at 6 months using telephone survey. 

 43
It should be noted that the two controlled studies (1DR and HMO49,50) both examined 

different levels of personalization of risk information, but only the HMO study49 examined the 

capture of family history information as an intervention in itself. The community pharmacy 

study48 did not have a control group without family history capture. 

Outcomes 

The findings of the evaluation studies of the interventions described above are summarized in 

Table 11. The 1DR study50 showed a borderline statistically significant difference (P=0.05) in 

the change in mammography uptake (about 8 percent) between intervention and control groups. 

The other two studies were null. The community pharmacy study48 was the only one to examine 

other behaviors, and showed a statistically significant increase in self-reported BSE, but not 

CBE. The HMO study appeared to be adequately statistically powered; this was also likely the 

case with the 1DR study although sample size considerations were not discussed. Although the 

community pharmacy study indicated an a priori sample size calculation, their assumptions 

about baseline adherence rates may have been erroneous, as they were around 70-80 percent for 

CBE and mammography, much higher than published general population figures and suggestive 

of a possible ceiling effect. 

All articles reported age-specific analyses, which generally did not show meaningful 

differences in effectiveness of the interventions. The HMO study49 also analyzed outcomes by 

breast cancer family history status (positive or negative) in the two groups that had been sent a 

risk questionnaire. While mammography uptake was similar between those receiving general risk 

and personalized risk invitations and who had a negative family history (41.4 and 39.7 percent, 

respectively), uptake was higher in women who had a positive family history and received a 

personalized invitation (66.7 percent) than women with a positive family history who received a 

generalized risk invitation (42.9 percent) (P=0.005). The results of the community pharmacy 

study48 were unchanged when the analyses were limited to the high risk participants only. 

The studies vary in the extent to which their participants were representative of the general 

population. The HMO study was designed to be completely representative of its own patient 

population, which was described in previous publication as predominantly white, slightly better 

educated, and having a slightly different income distribution than Washington state as a 

whole.171 The proportion of participants with a positive first or second degree family history of 

breast cancer was about 20 percent, which is consistent with the North American female 

population. In contrast, the 1DR study was confined to women who had at least one first degree 

relative with breast cancer. The community pharmacy study drew participants from women 

attending pharmacies and heart health events, and no specific data are presented regarding 

representativeness. Their analyses indicate that 21 of 140 (15 percent) participants were assigned 

to the high risk category (≥1.7 percent risk of breast cancer in 5 years), which appears higher 

than would be expected for an unselected female population in this age group. Also, the high 

baseline rates of CBE and mammography compared with published figures for the general 

population may indicate that this study has limited external validity. 

Quality Assessment of Studies 

Standardized quality assessment checklists were employed on the two studies that used a 

randomized trial design.49,50 The modified Jadad scores were 4 out of 8 for both studies.83 The 

 44
main problem areas for both studies were failure to report measures to achieve blinding, and 

neither explicitly described randomization procedures or measures to conceal allocation. Both 

studies implemented the intervention through mail-outs to participants, asking them to take a 

specific action (schedule a mammography), and the possibility for contamination was probably 

rather low, particularly for the 1DR study. The potential for bias in these studies therefore 

appears quite low. 

The third study48 was described in the report’s abstract as a ‘randomized, paired, pre-post 

study’, which is misleading. In our assessment, it was an uncontrolled pre-post study in which 

before-after outcomes for individual participants were analyzed as paired data. No control group 

was used and therefore no random allocation was possible. The potential for bias in this study is 

high, given that no assessment could be made of the influence of external factors, or placebo or 

Hawthorne effects. 

Conclusion 

Taken together, the three studies identified neither support nor refute the hypothesis that 

taking family history and using it to personalize risk of breast, ovarian, colorectal, or prostate 

cancer promotes lifestyle changes which reduce cancer risk, and/or greater adherence with 

preventive clinical interventions. All three studies focused on breast cancer, the interventions 

were heterogeneous, some including components beyond family history taking and 

personalization of risk. The interventions generally did not resemble the routine, personal 

interaction which might occur between a primary care professional and an individual patient, and 

the methodological rigor of the evaluations was variable. 

The HMO study49 was embedded in a routine screening invitation system, and therefore 

resembled regular clinical practice, albeit in a non-personal way. The evaluation was welldesigned and had a large sample size. This study (the oldest of the three reviewed) provides no 

evidence that personalization of risk information would be an effective overall strategy, but 

suggests that it might be worth exploring as a way of promoting risk reduction behavior in high 

risk sub-groups. 

The 1DR study50 provided evidence of a possible modest effect on mammography uptake of 

personalizing risk information for a group already likely to have higher than average personal 

risk perceptions. The intervention had several components, and it is impossible to separate out 

the individual effects of the family history collection, the personalization of risk information, and 

the materials designed to reinforce the importance of mammography. Even this thoughtfully 

designed intervention produced only a small increase in screening behavior. The transferability 

of the approach to a clinical setting, and the absolute size of benefits that would be achieved, is 

unclear. 

The community pharmacy study48 showed some evidence that personalized risk information 

could promote cancer prevention behavior, but the lack of a control group, the questionable 

validity of the outcome measurement, and the likely selection bias of participants all make it 

impossible to judge the wider applicability of its findings. 

 45
Research Q4: What are the Harms or Risks to Individual 

Patients That may Result From the Collection of Family 

History Information in Itself, and/or the Provision of Family 

History-Based Risk Information? 

General Approach 

We reviewed published intervention studies, (RCTs, controlled trials, and before-after 

studies) which assessed negative impacts of systematically collecting family history information 

and providing patients with risk information for the cancers of interest based on their family 

history. The focus was on systematic collection of individual family history information, and 

communication of personal risk of one or more of the cancers of interest, in populations 

considered representative of primary care populations. Specialist genetic counseling (with or 

without genetic testing) for patients selected because of possible genetic risk was excluded from 

this definition. 

The outcomes of interest were impaired quality of life, negative psychological effects 

(cognitive, affective, or behavioral), social impacts (e.g., negative impact on family well-being, 

discrimination, stigmatization), which could be directly attributed to this intervention, not 

subsequent clinical or other preventive activities. 

Studies Reviewed 

One study was identified which met all eligibility criteria.51 This was an uncontrolled beforeafter study designed to evaluate the psychological impact of providing family history information 

and receiving a personalized risk assessment. Patients aged 35-65 registered with a single family 

doctor’s office were invited to complete a postal cancer family history questionnaire, and were 

provided with individual feedback on their genetic risk of CRC and breast cancer (where 

appropriate). General anxiety and cancer worry was assessed at baseline and 4 to 6 weeks after 

risk information feedback using the Spielberger State-Trait Inventory (STAI) and a 

multidimensional cancer worry scale, respectively. Details of the study are summarized in Table 

12. 

 

Outcomes 

This study analyzed participants in two groups. Firstly, ‘lower risk’ (those at no more than 

slightly elevated risk) participants, for whom no followup was necessary, were given feedback 

by letter only. No statistical difference was observed in anxiety and most other cancer worry 

measures following the intervention, with the exception of a small reduction in participants’ 

perception of their own risk (P<0.01). 

Of the remaining participants, most were interviewed to clarify details of the family history, 

which led 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 anxiety and cancer worries scales was observed. However, both of these groups showed 

 46
 47

higher baseline cancer risk perception scores compared to the lower risk group (P<0.001 for 

‘higher risk’ group and P=0.003 for ‘false positive’ group). 

Overall, the findings suggested no association between the exercise of capturing family 

history information and feeding back personalized risk, and anxiety or cancer worry, in patients 

who are close to average risk. In fact, it is possible that the intervention may have led to more 

realistic (lower) perceptions of personal risk. In contrast, the higher anxiety and cancer worry 

outcomes in the ‘true’ and ‘false positive’ high risk groups may reflect their baseline (preintervention) status rather than an effect of family history taking. 

Conclusion 

The evidence base for addressing (Q4) is limited to a single study. It suggested that 

structured family history collection and feedback of breast cancer risk information had no 

deleterious psychological effects on any of the risk groups, and in women, who were not at high 

risk, may have led to appropriate reductions in perceived risk. Higher average baseline levels of 

anxiety and cancer worry in the groups who went on to have further assessment may reflect preexisting concerns about a positive family history and need to be taken into account when family 

history interventions are evaluated. 
Table 4. Details of risk prediction models 

System Cancer Family history items Other items Output Relevant studies 

Gail model (GM)15 Breast 1DRs with BC 

Age at first birth <20y (0, 1, ≥2) 20-24y (0, 1, ≥2) 

25-29 y or nulliparous (0, 1, ≥2) ≥30y (0, 1, ≥2) 

Age Ethnicity Age at menarche Age at first live birth # previous breast biopsies (0, 1, >1) Presence of atypical hyperplasia on biopsy 

Risk of BC Adams-Campbell10(2007) 

Spiegelman8(1994) 

Modified GM (MGM)84

Breast As for GM As for GM Risk of invasive 

BC 

Chlebowski13(2007) 

Adams-Campbell10(2007) 

Rockhill9(2001) 

Boyle11(2004) 

Decarli12(2006) 

MGM for black/African Americans (GMB)10

Breast As for GM As for MGM As for MGM Adams-Campbell10(2007) 

Abbreviations: 1DR=first degree relative; AUC=area under the curve; BC=Breast cancer; BCDDP=Breast Cancer Detection Demonstration Project; 

CRC=Colorectal cancer; E=Expected events; GM=Gail Model; GM-B=GM for blacks/African Americans; IT-GM=GM for Italian population; MGM=

events; NHS= National Health Service; RCT=Randomized controlled trial; RR=Relative risk; SEER=Surveillance, Epidemiology and End Results

48
Table 4. Details of risk prediction models (continued) 

System Cancer Family history 

items 

Other items Output Relevant studies 

MGM for Italian population (ITGM)11,12

Breast As for GM As for MGM, except # 

previous breast biopsies replaced by any breast biopsy (no, yes) 

As for MGM Boyle11(2004) 

Decarli12(2006) 

CARE model for African American population7

Breast Number of affected 

relatives (mother, sisters) 

Age Age at menarche # previous breast biopsies, (<50y, ≥50y) Presence of atypical hyperplasia on biopsy (Age at first live birth) 

As for MGM Gail 72007 

Harvard Cancer Risk Index 16

Colon Brother/sister/parent 

with colon cancer 

Red meat intake Vegetable intake Alcohol intake Multivitamin use Physical activity Body mass index Height Colonoscopy/sigmoidoscopy screening (Aspirin use) 

10 year cancer risk 

Kim 14 2004 

49
50

Table 5. Evaluations of risk prediction models 

Study 

Design Tool(s) Participants Outcome measure(s), timing ascertainment Algorithm performance Co

Spiegelman8

1994 

GM n=115,172 12 y BC incidence Calibration 

O, E E/O (95% CI) O=2,396, E=3,196 E/O=1.33 (1.28-1.39) Discrimination Correlation coefficient (Pearson) 0.67 (Spearman) 0.04 

Significant overesrisk Modest discrimina

Rockhill9

2001 

MGM n=82,109 5 y BC risk Calibration 

O, E E/O (95% CI) O=1,354, E=1,273.42 E/O=0.94 (0.89-0.99) Discrimination AUC (95% CI) 0.58 (0.56-0.60) RR=(95% CI) 2.83 (2.19-3.65) Sensitivity, specificity (cut point=1.67% 5 y risk): Se=0.44, Sp=0.66 

Fairly well calibraModest discrimina

Abbreviations: 1DR=first degree relative; AUC=area under the curve; BC=Breast cancer; CI=confidence interval; CRC=Colorectal cancer; E=Expec

GM-B=GM for blacks/African Americans; IT-GM=GM for Italian population; MGM=Modified GM; O=Observed events; NHS= National Health S

controlled trial; RR=Relative risk; Se=sensitivity; SEER=Surveillance, Epidemiology and End Results; Sp=specificity; y=years;

1Performance by other cut-off points also reported 
Table 5. Evaluations of risk prediction models (continued) 

Study 

Design Tool(s) Participants 

Outcome 

measure(s), 

timing 

ascertainment 

Algorithm performance Co

Chlebowski13

2007 

MGM n=147,916 

Mean age 63 y (range 50-79 y) “Ethnically diverse” Excluded: History of BC, mastectomy Suspicious baseline mammogram <5 y followup 

5 y invasive BC risk, assessed by annual or semiannual ascertainment by mail or telephone questionnaire Cancer verified through pathology reports 

Calibration O, E E/O O=3,236, E=2,562 E/O=0.79 (p<0.001) Discrimination AUC (95% CI) 0.58 (0.56-0.60) 

Poorly calibratenumber of invasabout 20% Modest discrimi

AdamsCampbell10

2007 

MGM GM-B 

n=1,450 Age: 21-69 y Enrolled 1995 Diagnosed with BC 1995-2003, aged ≥35 y 

(cases) Age-matched, no BC by 2003 

5 y invasive BC risk, assessed by biennial questionnaires 

Discrimination Sensitivity, specificity (cut point=1.7% 5 y risk) MGM Se=0.18, Sp=0.86 MGM-B Se=0.04, Sp= 0.97 

The MGM and Mat predicting risAfrican AmericaLimited discrimi

51
Table 5. Evaluations of risk prediction models (continued) 

Study 

Design Tool(s) Participants 

Outcome 

measure(s), 

timing 

ascertainment 

Algorithm performance Co

Boyle11

2004 Secondary analysis of RCT data 

172

IT-GM MGM 

n=5,383 Women had hysterectomies and no benign breast disease 

5 y BC incidence Calibration 

O, E E/O (95% CI) IT-GM O=79, E=82.5 E/O=0.92 (0.68-1.16) MGM O=79, E=88.4 E/O=0.86 (0.64-1.08) Discrimination AUC IT-GM 0.58 

Reasonably weModest discrimipopulation studData were misshyperplasia on 

52
Table 5. Evaluations of risk prediction models (continued) 

Study 

Design Tool(s) Participants 

Outcome 

measure(s), 

timing 

ascertainment 

Algorithm performance Co

Decarli12

2006 

IT-GM MGM 

n=10,031 Age: 35-64 

5 y invasive BC risk Method of ascertainment not reported in this paper. 

Calibration O, E E/O (95% CI) IT-GM O=194, E=186.11 E/O=0.96 (0.84-1.11) MGM O=194, E=180.1 E/O=0.93 (0.81-1.08) Discrimination Average age-specific AUC (95% CI) IT-GM 0.59 (0.54-0.63) MGM 0.58 (0.55-0.63) 

MGM and IT-GM Modest discrimipopulation stud

Gail7

2007 

CARE n=14,059 

Age:≥50 

5 y age-specific invasive BC risk 

Calibration O/E ratio (95% CI):1.08 (0.97-1.20) Discrimination Unweighted average age-specific AUC (95% CI): 0.555 (0.535-0.575) 

Good calibrationdiscriminatory a

53
Table 5. Evaluations of risk prediction models (continued) 

Study 

Design Tool(s) Participants 

Outcome 

measure(s), 

timing 

ascertainment 

Algorithm performance Co

Kim14

2004 

HCRI n=52,668 

Females Age: median 52 

10 y colon cancer incidence 

Calibration O/E(95% CI) Overall O/E not reported By HCRI category: 2.10≤RR≤5.10 1.79 (0.89-2.70) 1.10≤RR≤2.10 1.39 (1.12-1.67) 0.90≤RR≤1.10 1.00 (0.66-1.34) 0.50≤RR≤0.90 0.89 (0.68-1.09) 0.20≤RR≤0.50 0.58 (0.37-0.79) Discrimination AUC (95% CI): 0.67 (0.64-0.70) 

Good calibrationdiscriminatory p

54
Table 5. Evaluations of risk prediction models (continued) 

Study 

Design Tool(s) Participants 

Outcome 

measure(s), 

timing 

ascertainment 

Algorithm performance Co

Kim 14

2004 

HCRI n=38,953 

Males Age: median 51 

10 y colon cancer incidence 

Calibration O/E(95% CI) Overall O/E not reported By HCRI category: 2.10≤RR≤5.10 2.35 (1.12-3.59) 1.10≤RR≤2.10 1.34 (1.02-1.66) 0.90≤RR≤1.10 1.01 (0.64-1.39) 0.50≤RR≤0.90 0.75 (0.56-0.95) 0.20≤RR≤0.50 0.83 (0.60-1.07) Discrimination 

Poor calibration potential misclacohort at baselidiscrimination 

AUC (95% CI): 0.71 (0.68-0.74) 

55
56

Table 6. Target interventions for review Cancer Intervention Breast Chemoprevention 

Breast self-examination Clinical breast examination Screening mammography Screening MRI 

Ovarian Screening ultrasound Colorectal Chemoprevention 

FOBT screening Screening colonoscopy Screening sigmoidoscopy 

Prostate Chemoprevention 

PSA screening Digital rectal examination 

All Regular exercise/physical activity 

Dietary interventions - high fiber diet - high fruit and vegetables - low fat Vitamin and micronutrient supplementation Limitation of alcohol intake Smoking cessation Seeking health care advice Referral for genetic counseling and/or genetic testing, where criteria are met 

Abbreviations: FOBT=fecal occult blood test; MRI=magnetic resonance imaging; PSA=prostate specific antigen 
Table 7. Breast cancer preventive interventions 

Study 

Specific 

interventio

n(s) 

evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

of trials 

Followup 

duration 

(years) 

Sample 

sizes 

Ages 

Type of intervention: Chemoprevention (antioxidants, NSAIDS, and statins) Bardia18

2008 

Antioxidant supplementation: β-carotene Selenium Zinc Vitamin C Vitamin E or any others 

Quant People at 

average risk of cancer 

RCTs; Supplements with fully disclosed components and not dietary increases in nutrients; placebocontrolled; ≥1 y of followup; reported overall cancer incidence 

≤12 (n not reported for cancerspecific analyses) 

NR 88,392 

(total across all trials) 

NR B

(aR(

Abbreviations: BC=breast cancer; BSE=breast self-examination; DRE=digital rectal exam; e.g.=example; FOBT=fecal occult blood test; HP=High po

LP=Low potency; mg=milligrams; MP=Medium potency; NR=not reported; PHS=Physician’s Health Study; PSA=prostate specific antigen; Qual=QuRCT=Randomized controlled trial; RR=Relative risk; SM=Screening mammography; SR=systematic review; TRUS=transrectal ultrasound; y=year; W

57
Table 7. Breast cancer preventive interventions (continued)

Study 

Specific 

interventi

on(s) 

evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

of trials 

Followup 

duration 

(years) 

Sample 

sizes Ages 

Alkhenizan 19

2007 

Vitamin E alone Vitamin E as part of other supplements 

Quant ≥18 y; 

range of preexisting health states, but not high risk for BC 

RCTs; Supplementation in capsule or tablet form; control = placebo or no intervention; reported total mortality, cancer mortality, cancerspecific mortality 

3 ≥510 

days - ≤10 y (not reported separately for individual cancers) 

62,158 (total across all studies) 

NR B

(cR(

Browning20

2006 

Statins Quant All 

populations except highly specific statin-using patients (e.g. familial hypercholesterolemia, renal transplant) 

RCTs; Control = placebo; Reported all cancer, sitespecific cancer incidence or mortality 

1-7 (depending on analysis) 

Median followup: Trials: 3.6 y Observational studies: 6.2 y 

RCTs: n = 103,573 Observational studies: n = 826,854 

RCTs: 18-82 y Observational studies: 30-89 y 

Bfs1R(2R(3R(4R(5tR(

58
Table 7. Breast cancer preventive interventions (continued)

Study 

Specific 

interventi

on(s) 

evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

of trials 

Followup 

duration 

(years) 

Sample 

sizes Ages 

6tR(

Type of intervention: Screening Kosters21

2003 

BSE Quant General 

population 

RCTs 3 trials, 

1 discontinued China Russia 

10-12 122,471-

266,064 

30-74 1

m(afoR(

59
60

Table 7. Breast cancer preventive interventions (continued)

Study 

Specific 

interventi

on(s) 

evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

of trials 

Followup 

duration 

(years) 

Sample 

sizes Ages 

Gøtzsche 22

2006 

SM Quant Women 

without previously diagnosed BC 

RCTs; Controls with no SM 

3 ‘adequately randomized’ trials Canada 7 ‘suboptimally randomized’ trials 

7-13 42,482-

92,934 

39-74 A

B(R(SrtR(ArtR(AmR(SrtR(AmR(
Table 8. Colorectal cancer preventive interventions 

Study 

Specific 

interventio

n(s) 

evaluated 

Type 

of SR 

Eligible 

population

s 

Eligible 

study 

designs 

Number 

and type 

of trials 

Followp 

duration 

(years) 

Sample 

sizes Ages 

Type of intervention: Chemoprevention (antioxidants, NSAIDS, and statins) Bardia18

2008 

Antioxidant supplementation: β-carotene Selenium Zinc Vitamin C Vitamin E or any others 

Quant People at 

average risk of cancer 

RCTs; Supplements with fully disclosed components and not dietary increases in nutrients; placebocontrolled; ≥1 y of followup; reported overall cancer incidence 

≤12 NR 178,086 

(total across all studies) 

NR C

in(aR(

Abbreviations: ASA=acetylsalicylic acid; BC=breast cancer; BSE=breast self-examination; DRE=digital rectal exam; e.g.=example; FOBT=fecal occ

LI=Lipophilic; LO=Lipophobic; LP=Low potency; mg=milligrams; MP=Medium potency; NR=not reported; PHS=Physician’s Health Study; PSA=p

Qual=Qualitative; Quant=Quantitative; RCT=Randomized controlled trial; RR=Relative risk; SR=systematic review; TRUS=transrectal ultrasound; y

* Kerr review also examines FOBT screening alone, but results overlap, and are consistent, with those of Hewitson & Heresbach, therefore not reporte

61
Table 8. Colorectal cancer preventive interventions (continued) 

Study Specific 

intervention(

s) evaluated 

Typ

e of 

SR 

Eligible 

population

s 

Eligible 

study 

designs 

Number 

and type 

of trials 

Follow 

up 

duration 

(years) 

Sample 

sizes 

Ages 

Alkhenizan 19

2007 

Vitamin E alone Vitamin E as part of other supplements 

Quant 

≥18 y; range of pre-existing health states, but not high risk for colorectal cancer. 

RCTs; Supplementation in capsule or tablet form; control = placebo or no intervention; reported total mortality, cancer mortality, cancerspecific mortality 

2-4 depending on outcome

≥510 days - ≤10 y (not reported separately for individual cancers) 

24,114 - 91,099 (across all trials, depending on analysis) 

NR 1

in(cR(2in(R(

Dubé23

2007 

ASA Qua

nt and Qual 

“Average’ risk 

RCTs, controlled clinical trials 

2 PHS 325mg every other day WHS 100mg/day 

5-10 22,071-

39,876 

NR 1

m(ssbAm2inR(3in(R(

62
Table 8. Colorectal cancer preventive interventions (continued) 

Study Specific 

intervention(

s) evaluated 

Typ

e of 

SR 

Eligible 

population

s 

Eligible 

study 

designs 

Number 

and type 

of trials 

Follow 

up 

duration 

(years) 

Sample 

sizes 

Ages 

Browning20

2006 

Statins Qua

nt 

All populations except highly specific statin-using patients (e.g. familial hypercholesterolemia, renal transplant) 

RCTs; Control = placebo; Reported all cancer, sitespecific cancer incidence or mortality 

1-9 (depending on analysis) 

Median followup: Trials: 3.6 y 

RCTs: n = 103,573 

RCTs: 18-82 y 

Cinfs1R(2(R(3R(4tR(5(R(6tR(7tR(

63
Table 8. Colorectal cancer preventive interventions (continued) 

Study Specific 

intervention(

s) evaluated 

Typ

e of 

SR 

Eligible 

population

s 

Eligible 

study 

designs 

Number 

and type 

of trials 

Follow 

up 

duration 

(years) 

Sample 

sizes 

Ages 

Type of intervention: Population-based screening Hewitson24

2006 

FOBT (Hemoccult) investigation following positive screen result – colonoscopy or sigmoidoscopy and double contrast barium enema, with removal of colorectal cancers or adenomas found at diagnostic investigation 

Quant, Qual 

Adults; volunteers or individuals/households identified from primary care records or population registries 

RCTs (individual or groups); control = no screening; report results based on participation in >1 screening round; report colorectal cancer mortality 

4 10-17 46,551-

150,251 Total 329,642 

45-80 y 1

mgR(2m(sgR(3m(R(4mwm(R(5m(≥R(

64
65

Table 8. Colorectal cancer preventive interventions (continued) 

Study Specific 

intervention(

s) evaluated 

Typ

e of 

SR 

Eligible 

population

s 

Eligible 

study 

designs 

Number 

and type 

of trials 

Follow 

up 

duration 

(years) 

Sample 

sizes 

Ages 

Kerr25

2007 

Once-only flexible sigmoidoscopy in addition to FOBT test, followed by colonoscopy for investigation of positive screen result

*

Quant 

Not specified, but populationbased implied 

RCTs; control = no screening control for this study was FOBT alone 

1 2-5 10,978 50-75 1

mR(2inR(
Table 9. Prostate cancer preventive interventions 

Study 

Specific 

interventions 

evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

trials 

Followup 

durations 

(years) 

Sample 

sizes Ages 

e

Type of intervention: Chemoprevention Bardia18

2008 

Antioxidant supplementation: β-carotene Selenium Zinc Vitamin C Vitamin E or any others 

Quant People at 

average risk of cancer 

RCTs; Supplements with fully disclosed components and not dietary increases in nutrients; placebocontrolled; ≥1 y of followup; reported overall cancer incidence 

≤12 NR 55,709 

(total over all trials) 

NR P

cainAanR(0Salda“din[ER

(0

Abbreviations: NR=not reported; Quant=Quantitative *This review also reported data relating to antioxidants; not included under this review’s data as included in more recent included review18

66
Table 9. Prostate cancer preventive interventions (continued) 

Study 

Specific 

intervention

s evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

trials 

Followup 

durations 

(years) 

Sample 

sizes Ages 

e

Alkhenizan 19

2007 

Vitamin E alone Vitamin E as part of other supplements 

Quant 

≥18 y; range of preexisting health states, but not high risk for prostate cancer. 

RCTs; Supplementation in capsule or tablet form; control = placebo or no intervention; reported total mortality, cancer mortality, cancerspecific mortality 

2-4 (depending on outcome reported) 

≥510 days - ≤10 y (not reported separately for individual cancers) 

24,114-71,759 (total over all trials analyzed, depending on outcome reported) 

NR P

cain1. coR(02. R(03. otsuR(04. ≥3R(05. <3R(0

Bristol SLR Team26

2006*

Calcium supplements 

Quant NR; 

presumed cancer free 

All 1 RCT 11 

(intervention duration plus followup) 

672 61.8 

(mean) 

R(0

67
Table 9. Prostate cancer preventive interventions (continued) 

Study 

Specific 

intervention

s evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

trials 

Followup 

durations 

(years) 

Sample 

sizes Ages 

e

Browning 20

2006 

Statins Quant All 

populations except highly specific statin-using patients (e.g. familial hypercholesterolemia, renal transplant) 

RCTs; Control = placebo; Reported all cancer, sitespecific cancer incidence or mortality 

1 or 4 (depending on analysis 

Median followup: Trials: 3.6 y Observational studies: 6.2 yrs 

RCTs: n =103,573 Observational studies: n=826,854 

RCTs: 18-82 yrs Observational studies: 30-89 yrs 

1. cainR(02. cam(1 R(0

Type of intervention: Screening Ilic27

2007 

Any of  PSA  DRE TRUS biopsy 

Quant All men RCTs, 

quasirandomized, controlled trials; screening versus no screening 

2 RCTs Quebec Annual screening Round 1 = PSA + DRE + TRUS where PSA >3.0ng/ml and/or abnormal DRE Later rounds = PSA with TRUS biopsy of PSA >3ng/ml or increased 

11-15 9,026-

46,486 Total 55,512 

45-80 P

camR(0

68
Table 9. Prostate cancer preventive interventions (continued) 

Study 

Specific 

intervention

s evaluated 

Type 

of SR 

Eligible 

populations 

Eligible 

study 

designs 

Number 

and type 

trials 

Followup 

durations 

(years) 

Sample 

sizes Ages 

e

by >20% 3-yly screening Rounds 1&2=DRE Rounds 3&4=DRE + PSA. TRUS biopsy if DRE abnormal or PSA >4.0ng/ml 

*This review also reported data relating to antioxidants; please refer to more recent review included above18

69
Table 10. Details of family history and personalized risk interventions 

Study 

and 

study 

design 

Target 

population 

Target 

behavior 

Family history 

collection component 

of intervention 

Risk personalization 

component of intervention 

Other 

components 

Curry49

1993 RCT 

Women eligible for SM 

Having SM Mailed self-completion 

questionnaire: 1. Information on 1DR and 2DR with BC 2. Other risk factors: age, age at menarche, age at first birth, menopause status, age at menopause, previous mammography, history of biopsy 

Insertion of following text into a generic mammography invitation letter: “BC affects 1 in 10 women over their lifetime, but is more common with a personal history of particular risk factors. The recommendation that you schedule a comprehensive visit now is based on the answers you provided on the BC Screening Survey. From your responses, we were able to determine that your personal screening schedule is affected by your age [plus other risk factors if present]...” 

None 

Giles482001 BA 

General female population 

Having SM BSE CBE 

Intervieweradministered survey: 1. Number of 1DRs with BC 2. Other risk factors: age at menarche, age at first live birth, number of breast biopsies 3. Other: history of practicing BSE, formal instruction in BSE, confidence in performing BSE, history of mammography 

1. RR for developing BC in next 5y 2. RR for developing cancer in her lifetime 

Encouragement to follow ACS guidelines for mammography, BSE, CBE ACS instruction card on BSE NCI brochure on BC risk factors 

Abbreviations: 1DR=first degree relative; 2DR=second degree relative; ACS=American Cancer Society; BA=before-after; BC=breast cancer; BSE=brCBE=clinical breast examination; FH=family history; NCI=National Cancer Institute; RCT=randomized controlled trial; RR=relative risk; SM=screen

70
Table 10. Details of family history and personalized risk interventions (continued) 

Study 

and 

study 

design 

Target 

population 

Target 

behavior 

Family history 

collection component 

of intervention 

Risk personalization component 

of intervention 

Other 

components 

Bastani 50

1999 RCT 

Female relatives of breast cancer patients 

Having SM 

Current age age at menarche, age at first live birth, number of breast biopsies, and number of first-degree relatives with breast cancer age at first biopsy, age of the index case (first degree relative listed in cancer registry) with cancer, age at menopause 

List of personal risk factors for breast cancer and classification of risk in comparison with other women of the same age (“slightly”, “moderately”, or “substantially” higher risk) 

Other materials tailored for high-risk women” plus message regarding the importance of regular screening mammography 

71
Table 11. Evaluations of family history and personalized risk 

Study 

and 

study 

design 

Participants Control intervention/group Outcome measure(s) Effect of FH based intervention on target behavior(s) Modified Jadad quality score (max=8) 

Curry49

1993 RCT 

Women ≥50 y 

registered with a single HMO, eligible for SM n=2,076 

1. No risk data captured, generic invitation to schedule a mammogram (C1) 2. No risk data captured, general risk information included in invitation to schedule a mammogram (C2) 3. Risk data captured, general risk information included in invitation to schedule a mammogram (C3) 

Having a mammogram within 12 months of invitation 

% Received a mammogram by 12 months: I: 44.6% C1: 49.2% C2: 41.1% C3: 41.8% P=0.23 (Χ2) 

Comparison restricted to I&C3 only (risk factor questionnaire plus general risk or personalized risk invitation), stratified by family history: No family history – I: 39.7% C3: 41.4% Positive family history: I: 66.7% C3: 42.9% P=0.005. 

4 Overall, 

informatgeneral informatmammonot incresuggest informatrisk meseffective behavior 

Allocation concealment NR 

No significant interactions of personalized feedback with other risk factors 

Abbreviations: 1DR=first degree relative; BA=before-after; BC=breast cancer; BSE=breast self-examination; CBE=clinical breast examination; FH=f

applicable; NR=not reported; RCT=randomized controlled trial; SM=screening mammogram; 

* Confidence intervals not provided in original article, calculated on basis of data presented 

72
Table 11. Evaluations of family history and personalized risk (continued)

Study 

and 

study 

design 

Participants Control intervention/group Outcome measure(s) 

Effect of FH 

based 

intervention on 

target 

behavior(s) 

Modified 

Jadad 

quality score 

(max=8) 

Bastani50

1999 RCT 

Women with a 1DR with BC n=901 

1. Note thanking for participation in telephone survey 2. General information booklet on BC 

SM measured by self-report at 1 y followup 

% Had SM All ages: Baseline 

I: 55.0% C:54.9% Followup

I: 65.2% C: 57.7% P=0.05 30-40Baseline

I: 41.4% C:31.4% Followup

I: 49.4% C:35.7% P=0.66 40-50Baseline

I: 61.4% C: 57.4% Followup

I: 62.3% C:67.0% P=0.26 50-64Baseline

I: 58.9% C:68.8% Followup

I: 76.8% C: 68.8% P=0.02 

4 Allocation concealment NR 

In a someparticipanthe controtaking and BC, the ataking accindividualand reinfoof target bimprove ascreening modest ledifference 7% in absNo companot have 

73
Table 11. Evaluations of family history and personalized risk (continued)

Study 

and 

study 

design 

Participants Control intervention/group Outcome measure(s) 

Effect of FH 

based 

intervention on 

target 

behavior(s) 

Modified 

Jadad 

quality score 

(max=8) 

Giles482001 BA 

Women 

≥18y 

visiting a community pharmacy or attending a health screening event n=188 

None Adherence with 

ACS guidelines for BSE, CBE, and mammography, assessed at 6 months 

Proportions following ACS guidelines (selfreport) (% (95% CI*)) BSE All: Pre: 42/137 (31 (23-38)) Post: 77/137 (56 (48-64) P<0.001 5 y risk

≥1.7%: 

Pre: 4/20 (20 (2-37)) Post: 12/20 (60 (38-81)) P<0.005 CBE All: Pre:121/140 (86 (81-92)) Post:128/140 (91 (87-96)) P<0.09 5 y risk

≥1.7%: 

Pre: 17/21 (81 (61-98)) Post: 17/21 (81 (64-98)) P=1.00 Mammography All: ≥50y 

NA Findings s

personalizwhich incimprove arecommepractices of changethe three uniform ehigh risk pa control reliance othe small group anaconclusio

74
Table 11. Evaluations of family history and personalized risk (continued)

Study 

and 

study 

design 

Participants Control intervention/group Outcome measure(s) 

Effect of FH 

based 

intervention on 

target 

behavior(s) 

Modified 

Jadad 

quality score 

(max=8) 

Pre: 33/44 (75 (62-88)) Post: 31/44 (70 (57-84)) P<0.48 40-49 Pre: 18/32 (56 (39-73)) Post: 21/32 (66 (49-82)) P<0.257 5 y risk

≥1.7%: 

Pre: 17/21 (81 (64-98)) Post: 15/21 (71 (52-91)) P<0.317 

75
76

Table 12. Harm/risk of family history collection 

Author 

Year 

Setting 

Type of 

cancer 

Study 

design 

Characteristic 

of population 

1. No.recruited 

2. No.completed 

Time 

points 

for 

analysis 

(months) 

Duration of 

intervention 

followup 

Who 

delivered 

intervention? 

Leggatt51

2000 

Colorectal/colon/rectal Breast 

Before -After uncontrolled study 

Unselected patients aged 35 to 65 years 

1. 666 (29% response) 2. 604 

Baseline 1-1.5 

Postal survey followed by single session 

Lower risk group: letter from family doctor Potential increased risk groups: family doctor and/or oncologist/ geneticist 
Chapter 4. Discussion 

The purpose of this review was to establish the evidence base to answer the question, “In 

relation to the cancers of interest, would routinely taking and using family history for risk 

assessment in primary care settings be likely to lead to net health benefits?” Acknowledging the 

scope of this question, the evidence was assembled across a number of subsidiary questions, 

addressed individually below. 

Throughout the review, the focus was the primary care context. This led to two decisions 

which underpinned the review’s methodology, specifically the eligibility criteria. Firstly, across 

all questions, the populations studied had to reflect primary care populations. In practice, this 

meant that populations who already had cancer, a pre-cancerous condition, or who were 

suspected of carrying a genetic risk, were excluded. Secondly, studies of family history taking as 

a primary care intervention, i.e., as an intervention in and of itself, were included, but those 

where family history taking was approached as a specialist activity, and/or embedded within a 

larger set of clinical activities such as assessment for genetic testing, were excluded. 

We also drew a distinction between “taking family history” as a distinct activity practiced by 

health care providers (of central interest in this review) and “being aware of a positive family 

history” as an attribute of study participants. A patient’s ability to accurately report family 

history information is a prerequisite for valid family history collection. However, some people 

may also have a pre-existing perception of an unusually high family prevalence of cancer, 

leading to this being itself a cause of anxiety, quite separate from any effect of the clinical 

activity of taking a family history. Thus, evaluations of family history taking as an intervention 

need to be carefully designed to take account of this complicating factor. 

Risk Stratification Algorithms 

Many cancer risk stratification algorithms, models and systems exist, and the goal of this 

review was to identify which of those, based on family history information, performed well in 

primary care type populations. In approaching this question, we sought to identify evaluations of 

frameworks devised specifically for primary care, or which might be transferable to primary care 

even if originally designed for other purposes. 

Further, we were interested in evaluations which assessed the ability of a system to correctly 

predict risk in individuals, not simply on studies of overall associations between family history 

and disease incidence at a population level. As explained in Chapter 3, to be suitable for 

implementation in routine clinical settings, a risk prediction system needs to differentiate 

between the disease risk of individuals, such that it consistently predicts higher risk of cancer in 

those who are truly destined to go on to develop the disease than in those who will not. 

Review question (Q) 1 was therefore tightly focused on evaluations of models predicting 

individual risk, and this led to the exclusion of a large number of analytical epidemiological 

reports, descriptive clinical studies, and validation studies of models which did not present data 

on individual discriminatory accuracy (e.g., Constatino et al., 199984). We were able to identify 

evaluations of only two distinct approaches, one a family of models based on the Gail model15

(developed for breast cancer risk prediction), and the Harvard Cancer Risk Index16 (designed to 

predict the risk of a range of cancers, although validation data were available only for CRC). 

Both included a range of variables in addition to family history. 

77
The Gail model is publicly available on the National Cancer Institute’s web site 

(www.cancer.gov/bcrisktool/). It should be noted that its original purpose was epidemiological – 

to facilitate the design of clinical trials by permitting sample size calculations to be based on 

improved assumptions about expected disease outcome rates – rather than for clinical 

decisionmaking.15 Evaluations of this model indicated excellent performance at the population 

level, i.e., calibration, for predominantly white U.S. and Italian populations, judged by the ratio 

of expected to observed cases in the population studied. The model performed less well in more 

diverse U.S.13 or African American10 populations. The CARE model also showed good 

calibration.7

 

However, for all of these models, evaluations indicated generally modest discriminatory 

ability, with the c-statistic ranging from 0.55-0.59. Many women who would be judged to be 

high risk by one of these models would not go on to develop breast cancer, and vice versa. 

As a contrast, family history-based risk stratification has been found to perform much better 

as a predictor of coronary artery disease, with a c-statistic of 0.87.173 While family history can 

provide some useful predictive information on some common health conditions, the situation for 

breast cancer is less clear-cut. Although there are breast cancer family syndromes, these are 

associated with only about 5 percent of breast cancer cases. Over ninety percent of the incidence 

of breast cancer at a population level is not associated with a distinct familial pattern, and many 

women appear to develop breast cancer ‘out of the blue’. The known general risk factors – e.g., 

younger age at menarche, and later age at birth of first child – each contribute only a little to 

overall incidence of the disease (individual relative risks are modest), and they are reasonably 

prevalent in most populations 

Had the review found greater evidence of adequate discriminatory accuracy for some of these 

tools, this would not guarantee that their use would lead to better health outcomes in practice. A 

number of other conditions would need to be satisfied, for example evidence that different risk 

categories are matched with evidence on appropriate risk-specific preventive interventions. We 

note, for example, that the Gail and related models have been used primarily for assessing 

eligibility for cancer chemoprevention trials, although their use as more general clinical 

predictive tools is implied by their wider availability to the professional community and the 

general population. Stronger evidence is needed on the application of the tools in settings closer 

to routine clinical practice, and trials are required which directly assess the outcomes from risk 

assessment combined with risk-appropriate preventive interventions, not just assessments of the 

technical accuracy of risk prediction. Also, the use of tools needs to take into account standard of 

practice for the particular clinical context. As a hypothetical example, if guidelines were to 

recommend colonoscopy and polypectomy for all individuals with a family history of colorectal 

cancer, and this was widely implemented, and it led to a reduction in absolute colorectal cancer 

rates in the general population, then evaluations of risk prediction algorithms would need to 

consider the power implications of using cancer incidence as a primary outcome. 

Since the overall purpose of this review was to assess elements of the clinical utility of 

family history taking, we would ideally have liked to evaluate cancer risk stratification systems 

based solely on family history. At the time of writing, perhaps the prototypical system of interest 

is Family HealthwareTM,

174 a Web-based tool designed to assess a person’s familial risk for 

coronary heart disease, stroke, diabetes, and colorectal, breast, and ovarian cancer. It also 

provides users with personalized recommendations for lifestyle changes and screening. At the 

time of writing, evaluation data for this tool were not available. 

78
In the absence of validation studies of family history-based systems, we extended the review 

to include tools with a family history component. Despite this, a large number of predictive tools 

were excluded, either because they did not include any history items, some items would not be 

available for all patients, or would not routinely be available to a primary care practitioner. 

Further details of the wider range of risk prediction systems can be found at 

http://riskfactor.cancer.gov/cancer_risk_prediction/. 

Cancer Prevention Interventions 

Review (Q2) was an assessment of the overall benefits and harms of available preventive 

interventions for breast, ovarian, colorectal, and prostate cancers. As noted in Chapter 1, 

answering this question was an essential step in addressing the overall question of clinical utility 

of cancer family history taking, but cancer prevention in general was not the primary focus of 

this report. With a focus on published reviews of evidence, we again applied the criterion of 

primary care applicability in terms of unselected populations, which would be expected to 

contain individuals at high, medium, and low risk. Reviews were excluded only where they 

specifically focused on studies of high risk populations such as those affected by cancer or 

known pre-cancerous conditions, or people at known or suspected high risk of an inherited 

genetic disorder. Thus, while all reviews focused on “general” populations, none specified 

having relatives with cancer (but not suspicion of inherited genetic disorder) as an exclusion 

criterion. Most did not in fact specify this one way or the other, except one23 which explicitly 

stated that studies with participants with a positive family history of cancer were eligible. In the 

end, none of the reviews actually reported results separately for studies of participants with 

affected relatives, likely reflecting a lack of such primary studies. 

We also decided to focus on reviews of intervention studies, noting (for example) how 

apparently clear-cut evidence from observational epidemiological studies in the areas of betacarotene and lung cancer71-73 and hormone replacement therapy and breast cancer175 has been 

contradicted by subsequent randomized controlled trials.74,176 Where more than one eligible 

review was identified, we included the data from the most recent and highest quality review. We 

found no reviews relating to primary or secondary prevention of ovarian cancer. 

With respect to primary prevention of the cancers of interest, we found a striking lack of 

experimentally-derived evidence. We do not suggest, however, that this lack of evidence of 

effectiveness means that the interventions examined are ineffective. A number of issues and 

limitations must be considered. 

Firstly, there is the difficulty of translating the exposures examined in many observational 

studies into implementable interventions in trial settings. Observations on the potential protective 

effect of specific antioxidants, micronutrients, and vitamins have generally been derived from 

analyses of dietary habits or supplements containing multiple vitamins and minerals, whereas 

intervention studies generally investigated the effects of one or two supplemental agents in 

factorial trials. Moreover, in some instances, notably the Alpha-Tocopherol, Beta-Carotene 

Cancer Prevention Study, the doses of these agents were substantially higher than the exposures 

obtained through dietary and multivitamin supplements. Hence, few intervention trials have 

investigated ‘whole diet interventions’. To take calcium as an example, pooled analyses of 

cohort studies indicate an approximately 15 percent reduction in risk of colorectal neoplasia 

associated with higher dietary calcium intake,45 but no reviews were available of dietary calcium 

as an intervention in cancer prevention. Also, chemoprevention interventions may act early in 

79
cancer development, meaning that preventive effects may only be observable in long-term 

studies, not reflected in the followup timing reported in many of the primary trials contained in 

the reviews. 

A second issue is the baseline population risk, and the power of meta-analyses to detect an 

intervention effect. Taking calcium as an example again, we note that reviews which have 

conducted pooled analyses of studies conducted in higher risk populations (e.g., patients with 

adenomatous polyps, therefore excluded from the present review) have demonstrated an apparent 

20 percent lower recurrence rate amongst those randomized to calcium supplementation than 

those on placebo.177 It is perhaps worth noting that evidence of possible preventive effects of 

vitamin E19 and of calcium26 was noted in relation to prostate cancer; although the latter review 

met our (Q2) eligibility criteria in that the primary studies had recruited participants not at high 

risk for prostate cancer, the data came from a secondary analysis of a study with participants at 

elevated risk of colorectal cancer (the prostate outcomes being a secondary analysis).47 There is a 

current stream of thinking suggesting that there may be some common etiological pathways for 

prostate and colorectal cancer.178,179 This might mean that these apparently unselected 

participants were de facto at elevated risk of prostate cancer because they were at elevated risk of 

colorectal cancer. 

The focus on reviews also meant that we did not include large primary studies of 

interventions which have not yet been the subject of reviews. The report finds itself in the 

anomalous situation where some included reviews were based on analyses of single trials (and 

therefore, effectively present single trial data), but where interventions evaluated in large single 

trials were excluded on the basis of ineligible design (i.e., not a review). It was not possible, at 

the outset, to predict the results of the literature search for review (Q2) and to anticipate this 

situation. Extending (Q2) to include primary studies would have been a significant undertaking 

and was beyond the resources available for this review. We acknowledge that this has probably 

resulted in the exclusion of data on cancer prevention interventions which suggest protective 

effects. For example, one study180 was legitimately excluded, which reported a large combined 

analysis of two selected RCTs along with a systematic review restricted to observational studies. 

This study was not eligible because the systematic review element excluded intervention studies, 

and the two RCTs reported represented selective reporting of all relevant trial evidence. The two 

RCTs were designed primarily to assess the effects of acetylsalicylic acid (ASA) on non-cancer 

outcomes181,182 but had extended followup to examine the effects on cancer.180 The pooled 

analysis of the two trials (ASA assigned at doses of 300mg, 500mg or 1200mg per day) 

suggested a protective effect on colorectal cancer incidence at ten years (pooled relative risk 0.74 

(95 percent CI 0.56-0.97)). The magnitude of effect was consistent with observational studies, 

and no effect on the incidence of other types of cancer was observed. 

Despite extensive investment in cancer research over the last four decades, underlying 

mechanistic pathways for individual cancers still remain to be fully elaborated. Thus, the ‘risk 

factor’ approach of many analytical observational studies is an insufficient basis for drawing 

definitive conclusions on biological mechanisms of cancer causation and prevention. Emphasis is 

now being placed on large-scale prospective cohort studies with associated biobanks that hold 

promise of improved exposure assessment, and that will enable joint effects of genes and 

exposures to be investigated with adequate statistical power.183 

The evidence regarding screening for the cancers of interest provided greater clarity than that 

for primary prevention. As for secondary prevention, we found no reviews of screening or 

surveillance interventions relating to ovarian cancer. Regarding breast cancer, there appears to be 

80
clear evidence, on the basis of a pooled analysis of three large population-based trials, that 

teaching women breast self-examination and encouraging them to carry it out regularly has no 

measurable effect on breast cancer mortality. In some countries, the emphasis has shifted from 

exhorting women to examine their breasts monthly to becoming ‘breast aware’ – being familiar 

with what is ‘usual’ over a monthly cycle and therefore being able to identify and act on what is 

not ‘normal’.184

A large number of reviews of population-based mammography screening have been 

conducted, and the evidence seems to suggest that it reduces breast cancer mortality by about 15 

percent. The evidence is most clear cut for women aged 50 and over, the impact being limited in 

younger women by greater breast density and lower baseline risk. There is debate about the 

validity of using cancer-specific mortality as the primary outcome for evaluations of 

mammography screening; arguments revolve around the possibility of bias in the coding of death 

between screened and control populations, and the notable lack of impact of screening on all 

cause mortality. Where trials have demonstrated a reduction in mortality, there is no suggestion 

that annual screening offers benefits over biennial screening in women aged 50 or older. This 

also holds for younger age groups, although the lower sensitivity of the test and evidence of the 

more rapid growth of tumors in younger women have led some experts to suggest more frequent 

screening to maximize sensitivity.185,186 

Regarding colorectal cancer, the evidence appears to indicate that fecal occult blood testing 

(FOBT) and followup with colonoscopy reduces colorectal cancer mortality. The very limited 

evidence (one trial) suggests that flexible sigmoidoscopy does not improve this outcome, and 

there is no consensus on the optimum screening interval. Observers have also noted the lack of 

impact of screening on overall mortality, and some analyses have indicated an increase in noncolorectal cancer mortality. Although a 2008 U.S. Preventive Services Task Force (USPSTF) 

report187 contains a Grade A recommendation which includes colonoscopy as a screening 

intervention for colorectal cancer in individuals aged 50-75 years, the background evidence 

report188 indicates that no trials of colonoscopy as a stand-alone screening intervention were 

identified. 

We found no evidence of an effect of prostate specific antigen (PSA)-based screening 

strategies on prostate cancer mortality. In a recent USPSTF review, two RCTs were identified 

that did not show a mortality benefit from PSA screening independently or in a meta-analysis; 

important flaws in design and analysis were noted.189 The USPSTF review also identified one 

cross-sectional and two prospective cohort studies of possible psychological effects of PSA 

screening results. These suggested that false-positive PSA screening results cause psychological 

adverse effects for up to 1 year after the test. 

Although we sought reviews of ultrasound screening for ovarian cancer as an intervention, 

we did not consider reviews of other interventions such as CA-125 screening. In retrospect, it 

would have been legitimate to include this since the report also reviewed PSA-based screening 

for prostate cancer, which is an analogous serum-based cancer screening test. We note that the 

USPSTF positively recommended against screening general using CA-125 in a 2004 report,190

suggesting that the possibility of earlier detection would lead to small effects, at best, on 

mortality (because of the low prevalence of ovarian cancer therefore low positive predictive 

value), and fair evidence of important harms because of the invasive nature of diagnostic 

investigations. 

We also did not review genetic testing as an intervention, considering this not to be in itself a 

preventive intervention, but we did include the broader interventions of referral for genetic 

81
counseling and/or testing as interventions of interest applied to populations not considered high 

genetic risk. However, no reviews on these interventions were identified. 

Family History-Based Risk Assessment and Individual Preventive 

Behaviors 

It is postulated that knowing one’s genetic risk of disease, whether through a genetic test or 

family history, can provide a motivation to comply with advice on preventive interventions191

and some descriptive studies suggest that people who have a family history are overrepresented 

in studies of screening adherence.192-198 Noting concerns discussed in Chapter 1 about 

distinguishing between the behavior of people motivated by pre-existing perceptions of elevated 

disease risk because of living with a “family disease” from the effects of family history-based 

clinical strategy, we focused on intervention studies where the effects of confounding would be 

less evident. We found only three relevant primary studies, all of them relating to breast cancer 

prevention. One of them sampled women known to have a first degree relative with breast 

cancer50 (although not, by definition, formally identified as being at elevated genetic risk 

themselves), one was health organization-based,49 and the third likely comprised participants 

who were more than typically interested and generally compliant with some screening 

recommendations.48 The only study which in any way replicated a primary care consultation 

involving personal interaction between a health care professional and an individual patient was 

the third of these studies, which was in the setting of a community pharmacy,48 but was limited 

by its uncontrolled design. The participants appeared to have had an atypically high average 

adherence rate with screening mammography recommendations at baseline, which could have 

resulted in apparent lack of effect because there was little room for improvement (a possible 

“ceiling effect”). The overall evidence was therefore equivocal, neither confirming nor 

undermining the hypothesis that systematic feedback of risk motivates compliance. 

 

Direct Harms or Risks From Family History-Based Risk Assessment 

All health care interventions should be assessed for evidence of harm as well as benefit. We 

identified only one study relevant to family history taking that was conducted in an unselected 

primary care population. The respondents who were not found to be at elevated cancer risk had 

no evidence of adverse psychological outcomes, and in fact there was some indication that the 

assessment was beneficial in that it promoted more realistic personal risk perceptions. In 

contrast, participants whose initial assessments indicated potential elevated risk had higher 

baseline anxiety levels than those whose initial assessments indicated population risk, 

irrespective of their final risk assessment. In other words, both “true positives” and “false 

positives” had higher average pre-test anxiety levels which might suggest that perception of 

family history-associated cancer risk (whether confirmed or not) rather than collection of family 

history information might be associated with higher levels of anxiety. 

This single study is insufficient to conclude that family history taking as a deliberate clinical 

strategy is, in itself, likely to be harmful in terms of emotional impact, but it is consistent with 

findings from studies of genetic testing. It suggests that assessments of psychological status 

might be appropriate before embarking on family history-based risk assessments in order to 

identify those individuals who might be most at risk of ongoing anxiety or cancer-related worry, 

82
and who might therefore warrant extra support or counseling, irrespective of their actual assessed 

disease risk. 

Limitations 

 The eligible studies within this systematic review were limited to primary studies and 

systematic reviews in the English language. We restricted the search of systematic reviews to 

2003 forward, to ensure that only relatively recent reviews were selected. The review was also 

limited to studies in adults; therefore no conclusions can be drawn with respect to children or 

young people specifically. 

 The effectiveness of family history-based tools and interventions are dependent on the 

accuracy of reporting of family history, and it is impossible to comment on this aspect of the 

topic. We did not restrict studies according to the manner in which cancer family history was 

collected and considerable variation in the methods used was observed. Almost universally, 

studies depended on self-report methods and are therefore dependent on the individual 

respondents’ knowledge of their history. This represents a limitation on family history taking in 

practice rather than a limitation specifically of the review, and was explored in a previously 

published review.5

In examining the effects of family history taking on behavior (Q3), the eligibility criteria 

specified the intervention as feeding back family history-based risk alone, or with risk advice. 

We did not examine taking family history itself as an intervention without some element of 

feedback to a patient. The studies identified also evaluated interventions which were not terribly 

reflective of day-to-day primary care practice. It is therefore impossible to comment on whether 

the capture of family history information might lead a practitioner to consider different 

preventive strategies, or the incorporation of family history information into the broader 

knowledge of a patient might lead to changes in the nature or emphasis of preventive advice 

which is offered. The emphasis on very specific clinical behavioral outcomes also does not allow 

for exploration of other effects on the part of patients, e.g., seeking out more extensive 

information from family members as a result of having been asked “the first” set of questions on 

family history. 

 In regard to cancer prevention interventions, we were able to provide only an overview of 

classes of interventions and could not examine differences in their individual implementation 

(e.g., different doses). For reviews that assessed the same intervention, we selected the single 

best review based on several factors including number of studies and year of publications and 

methodological quality of the review.17 We did not contact authors for additional clarification for 

QUOROM requirements. Neither did we re-abstract or re-analyze original randomized trials 

eligible within the systematic reviews. In addition, as discussed above, the emphasis on reviews 

inevitably resulted in the exclusion of RCTs which had not been incorporated into reviews, 

including large studies such as the Women's Health Initiative trial of a dietary modification 

program on the incidence of colorectal cancer in post-menopausal women.199 We believe that, 

where interventions have been evaluated in primary trials which have then been included in 

published reviews, we have captured and reported the effectiveness evidence objectively; 

however, we believe that relevant effectiveness evidence for some interventions, based on welldesigned trials, has been missed wholesale because primary intervention studies were not eligible 

for (Q2). 

83
Conclusions 

1. The evidence for the predictive accuracy of algorithms in primary care populations was very 

limited. Although many tools were identified that incorporated some family history information, 

no evaluations of solely family history-based tools were identified. The tools on which it was 

possible to comment related mainly to breast cancer. 

Recommendations for future research: 

• The actual performance of tools based only on family history should be formally 

examined in primary prospective studies, and/or in secondary analysis of large cohort 

studies. 

• The performance of individual family history components of different risk 

stratification models which use a wider range of factors (including those examined in 

this report) should be examined separately from the non-family history components, 

in order to determine whether they provide sufficient predictive power in the absence 

of the non-family history factors. 

• For clinical relevance, the focus of validation should be discriminatory accuracy at 

the individual patient level. 

• More definitive evaluation should examine the effect on health outcomes when risk 

stratification systems are used in combination with preventive interventions, in actual 

practice settings. This cannot be done with secondary analyses of observational data 

and requires well-designed intervention studies. 

2. The evidence establishing the efficacy of interventions for primary and secondary prevention 

based on systematic reviews of randomized or controlled clinical studies in unselected 

populations is very limited. Interventions for which there were reviews include chemoprevention 

(antioxidants, calcium, NSAIDS, and statins) and screening interventions (BSE, mammography, 

FBOT, flexible sigmoidoscopy, and PSA) for breast, colorectal and prostate cancers. No reviews 

were found for ovarian cancer. It is likely that this review excluded effectiveness data available 

from RCTs of interventions which have not yet been the subject of systematic reviews. 

Recommendations for future research: 

• The large amount of evidence on potential primary cancer preventive interventions 

obtained from observational studies of cancer risk factors should continue to be 

further evaluated in well-designed randomized controlled trials. 

• Further systematic reviews should be conducted to examine the full range of 

potentially preventive interventions 

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 family history and using it to personalize risk of breast, ovarian, 

colorectal, or prostate cancer. 

Recommendations for future research: 

• Well-designed trials are required that compare family history-based, personalized risk 

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

levels (including population risk). 

84
85

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

from the routine practice of taking family history and using it to personalize risk information. 

Recommendations for future research: 

• Trials of family history taking as an intervention should include capture of data to 

examine the full range of potential impacts on individuals. Baseline data on 

psychological status should be captured so that this can formally be adjusted for in 

outcome analyses. 

5. Research on the use of family history tools, risk stratification systems, and family historybased personalized prevention advice should take into account evidence on the factors likely to 

promote their effective use in practice, such as the educational needs of primary care 

practitioners and issues which act as barriers or constraints to their implementation in practice.
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Appendix A – Search Strategies Detailed 

Question 1 

Ovid-MEDLINE 

1. claus.tw. 

2. gail.tw. 

3. BRCAPRO.tw. 

4. BOADICEA.tw. 

5. UK cancer family study group.tw. 

6. UKCFSG.tw. 

7. Myriad.ti,ab. 

8. tyrer Cuzick.ti,ab. 

9. ((Amsterdam or Bethesda or Manchester or Gilpin or Evans or Frank or Finnish or Yale or 

Spanish) adj5 (criteria or guideline? or scor$ or model? or protocol? or algorithm?)).ti,ab. 

10. FHAT.ti,ab. 

11. (Australia adj5 breast cancer cent$).tw. 

12. couch.ti,ab. 

13. ((mendel or LAMBDA) adj5 (criteria or guideline? or scor$ or model? or protocol? or 

algorithm?)).ti,ab. 

14. (Dutch guideline adj7 breast).ti,ab. 

15. (nice guideline? and breast cancer).ti,ab. 

16. or/1-15 

17. models, statistical/ 

18. models, theoretical/ or models, genetic/ 

19. 17 or 18 

20. genes, brca1/ or genes, brca2/ 

21. BRCA$.tw. 

22. 20 or 21 

23. 19 and 22 

24. 16 or 23 

25. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

26. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

27. *Neoplasms/ 

28. or/25-27 

29. validation.ti. 

30. accuracy.ti. 

31. validation studies/ 

32. evaluation studies/ 

33. exp "Sensitivity and Specificity"/ 

34. "reproducibility of results"/ 

35. odds ratio/ 

36. multivariate analysis/ 

37. exp Probability/ 

A-1
38. predictive value?.ti,ab. 

39. or/29-38 

40. 24 and 28 and 39 

41. animals/ not (humans/ and animals/) 

42. 40 not 41 

43. limit 42 to english language 

44. limit 43 to yr="1990 - 2008" 

45. Breast Neoplasms/ 

46. exp Colorectal Neoplasms/ 

47. exp Prostatic Neoplasms/ 

48. exp Ovarian Neoplasms/ 

49. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or 

carcinom$)).ti,ab. 

50. or/45-49 

51. exp Mass Screening/ 

52. (surveillance or screening).ti. 

53. Primary Prevention/ 

54. Preventive Medicine/ 

55. prophylactic.ti. 

56. prevention.ti. 

57. (genetic adj2 (counsel?ing or test$)).ti. 

58. Risk Assessment/ 

59. (risk adj (assessment? or stratification)).ti. 

60. Preventive Health Services/ 

61. or/51-60 

62. exp Pedigree/ 

63. limit 62 to humans 

64. exp Medical History Taking/ 

65. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti,ab. 

66. anamnesis.ti. 

67. (human adj2 pedigree).ti,ab. 

68. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

69. genogram$.ti,ab. 

70. ((famil$ or heredi$ or inherit$) adj3 (cancer$ or carcinom$ or neoplasm$)).ti,ab. 

71. (genetic adj2 (screening or test$)).ti,ab. 

72. Family Health/ 

73. or/63-72 

74. exp Neoplasms/ 

75. (neoplasm? or carcinoma? or cancer?).ti. 

76. 74 or 75 

77. guideline.pt. 

78. practice guideline.pt. 

79. guideline?.ti. 

80. or/77-79 

81. 73 and 76 and 80 

82. 50 and 61 and 80 

A-2
83. 81 or 82 

84. (note or comment or editorial).pt. 

85. 83 not 84 

86. limit 85 to english language 

87. limit 86 to yr="2003 - 2008" 

88. 44 or 87 

Ovid-EMBASE 

1. claus.tw. 

2. gail.tw. 

3. BRCAPRO.tw. 

4. BOADICEA.tw. 

5. UK cancer family study group.tw. 

6. UKCFSG.tw. 

7. Myriad.ti,ab. 

8. tyrer Cuzick.ti,ab. 

9. ((Amsterdam or Bethesda or Manchester or Gilpin or Evans or Frank or Finnish or Yale or 

Spanish) adj5 (criteria or guideline? or scor$ or model? or protocol? or algorithm?)).ti,ab. 

10. FHAT.ti,ab. 

11. (Australia adj5 breast cancer cent$).tw. 

12. couch.ti,ab. 

13. ((mendel or LAMBDA) adj5 (criteria or guideline? or scor$ or model? or protocol? or 

algorithm?)).ti,ab. 

14. (Dutch guideline adj7 breast).ti,ab. 

15. (nice guideline? and breast cancer).ti,ab. 

16. or/1-15 

17. MATHEMATICAL MODEL/ or STATISTICAL MODEL/ or CANCER MODEL/ or 

GENETIC MODEL/ 

18. GENETIC ALGORITHM/ or ALGORITHM/ 

19. or/17-18 

20. Brca1 Protein/ or Brca2 Protein/ 

21. oncogene/ 

22. brca2 gene/ 

23. BRCA$.tw. 

24. or/20-23 

25. 19 and 24 

26. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

27. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

28. *Neoplasms/ 

29. or/26-28 

30. 16 or 25 

31. 29 and 30 

32. validation.ti. 

33. accuracy.ti. 

A-3
34. agreement.ti. 

35. VALIDATION STUDY/ or INSTRUMENT VALIDATION/ or VALIDATION PROCESS/ 

36. diagnostic accuracy/ 

37. exp statistical parameters/ 

38. prediction/ 

39. "SENSITIVITY AND SPECIFICITY"/ 

40. predictive value?.ti,ab. 

41. or/32-40 

42. 31 and 41 

43. limit 42 to human 

44. limit 43 to english language 

45. limit 44 to yr="1990 - 2008" 

46. exp Neoplasms/ 

47. (neoplasm? or carcinoma? or cancer?).ti. 

48. 46 or 47 

49. exp Breast Cancer/ 

50. exp Colon Cancer/ 

51. exp Ovary Cancer/ 

52. exp Prostate Cancer/ 

53. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

54. or/49-53 

55. exp anamnesis/ 

56. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti,ab. 

57. anamnesis.ti. 

58. (human adj2 pedigree).ti,ab. 

59. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

60. ((famil$ or heredi$ or inherit$) adj3 (cancer$ or carcinom$ or neoplasm$ or tumo?r$)).ti,ab. 

61. (genetic adj2 (screening or test$)).ti,ab. 

62. genogram$.ti,ab. 

63. or/55-62 

64. prevention/ or primary prevention/ or prophylaxis/ or breast care/ or cancer prevention/ or 

chemoprophylaxis/ or periodic medical examination/ or personal monitoring/ or secondary 

prevention/ 

65. screening/ or screening test/ or mass screening/ or cancer screening/ or genetic screening/ 

66. risk/ or genetic risk/ or risk assessment/ or risk factor/ or risk management/ or risk reduction/ 

67. preventive medicine/ 

68. preventive health service/ 

69. prevention.ti. 

70. prophylactic.ti. 

71. or/64-70 

72. (note or comment or editorial).pt. 

73. practice guideline/ 

74. guideline?.ti. 

75. 73 or 74 

76. 48 and 63 and 75 

A-4
77. 54 and 71 and 75 

78. 76 or 77 

79. 78 not 72 

80. limit 79 to human 

81. limit 80 to english language 

82. limit 81 to yr="2003 - 2008" 

83. 45 or 82 

Ovid-CINAHL 

1. claus.tw. 

2. gail.tw. 

3. BRCAPRO.tw. 

4. BOADICEA.tw. 

5. UK cancer family study group.tw. 

6. UKCFSG.tw. 

7. Myriad.ti,ab. 

8. tyrer Cuzick.ti,ab. 

9. ((Amsterdam or Bethesda or Manchester or Gilpin or Evans or Frank or Finnish or Yale or 

Spanish) adj5 (criteria or guideline? or scor$ or model? or protocol? or algorithm?)).ti,ab. 

10. FHAT.ti,ab. 

11. (Australia adj5 breast cancer cent$).tw. 

12. couch.ti,ab. 

13. ((mendel or LAMBDA) adj5 (criteria or guideline? or scor$ or model? or protocol? or 

algorithm?)).ti,ab. 

14. (Dutch guideline adj7 breast).ti,ab. 

15. (nice guideline? and breast cancer).ti,ab. 

16. or/1-15 

17. practice guidelines.pt. 

18. Practice Guidelines/ 

19. guidelines.ti,ab. 

20. or/17-19 

21. exp Medical History Taking/ 

22. exp Family Health/ 

23. exp Pedigree/ 

24. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti,ab. 

25. anamnesis.ti,ab. 

26. (human adj2 pedigree).ti,ab. 

27. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

28. ((famil$ or heredi$ or inherit$) adj3 (cancer$ or carcinom$ or neoplasm$ or tumo?r$)).ti,ab. 

29. or/21-28 

30. exp Breast Neoplasms/ 

31. exp Colorectal Neoplasms/ 

32. exp Ovarian Neoplasms/ 

33. exp Prostatic Neoplasms/ 

34. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

A-5
35. or/30-34 

36. cancer screening/ or genetic screening/ 

37. (surveillance or screening).ti. 

38. Preventive Health Care/ 

39. Chemoprevention/ 

40. Risk Assessment/ 

41. prophylactic.ti. 

42. prevention.ti. 

43. (gentic adj2 (counsel?ing or test$ or screen$)).ti. 

44. Genetic Counseling/ 

45. (risk adj (assessment? or stratification)).ti. 

46. or/36-45 

47. exp Neoplasms/ 

48. (neoplasm? or carcinoma? or cancer?).ti. 

49. or/47-48 

50. 20 and 29 and 49 

51. 20 and 35 and 46 

52. 50 or 51 

53. limit 52 to (book chapter or case study or commentary or editorial) 

54. 52 not 53 

55. limit 54 to english 

56. limit 55 to yr="2000 - 2008" 

57. limit 55 to yr="2003 - 2008" 

58. models, theoretical/ or models, statistical/ 

59. Genes, BRCA/ 

60. BRCA$.tw. 

61. 59 or 60 

62. 58 and 61 

63. 16 or 62 

64. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

65. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

66. 64 or 65 

67. 63 and 66 

68. limit 67 to english 

69. (book chapter or case study or commentary or editorial).pt. 

70. 68 not 69 

71. limit 70 to yr="1990 - 2008" 

72. 57 or 71 

Ovid-CCRT 

1. claus.tw. 

2. gail.tw. 

3. BRCAPRO.tw. 

4. BOADICEA.tw. 

A-6
5. UK cancer family study group.tw. 

6. UKCFSG.tw. 

7. Myriad.ti,ab. 

8. tyrer Cuzick.ti,ab. 

9. ((Amsterdam or Bethesda or Manchester or Gilpin or Evans or Frank or Finnish or Yale or 

Spanish) adj5 (criteria or guideline? or scor$ or model? or protocol? or algorithm?)).ti,ab. 

10. FHAT.ti,ab. 

11. (Australia adj5 breast cancer cent$).tw. 

12. couch.ti,ab. 

13. ((mendel or LAMBDA) adj5 (criteria or guideline? or scor$ or model? or protocol? or 

algorithm?)).ti,ab. 

14. (Dutch guideline adj7 breast).ti,ab. 

15. (nice guideline? and breast cancer).ti,ab. 

16. or/1-15 

17. models, statistical/ 

18. models, theoretical/ or models, genetic/ 

19. 17 or 18 

20. genes, brca1/ or genes, brca2/ 

21. BRCA$.tw. 

22. 20 or 21 

23. 19 and 22 

24. 16 or 23 

25. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

26. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

27. *Neoplasms/ 

28. or/25-27 

29. validation.ti. 

30. accuracy.ti. 

31. validation studies/ 

32. evaluation studies/ 

33. exp "Sensitivity and Specificity"/ 

34. "reproducibility of results"/ 

35. odds ratio/ 

36. multivariate analysis/ 

37. exp Probability/ 

38. predictive value?.ti,ab. 

39. or/29-38 

40. 24 and 28 and 39 

41. limit 40 to yr="1990 - 2008" 

42. Breast Neoplasms/ 

43. exp Colorectal Neoplasms/ 

44. exp Prostatic Neoplasms/ 

45. exp Ovarian Neoplasms/ 

A-7
46. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or 

carcinom$)).ti,ab. 

47. or/42-46 

48. exp Mass Screening/ 

49. (surveillance or screening).ti. 

50. Primary Prevention/ 

51. Preventive Medicine/ 

52. prophylactic.ti. 

53. prevention.ti. 

54. (genetic adj2 (counsel?ing or test$)).ti. 

55. Risk Assessment/ 

56. (risk adj (assessment? or stratification)).ti. 

57. Preventive Health Services/ 

58. or/48-57 

59. exp Pedigree/ 

60. limit 59 to humans 

61. exp Medical History Taking/ 

62. ((family or familial) adj3 (histor$ or history-taking or risk$)).ti,ab. 

63. anamnesis.ti. 

64. (human adj2 pedigree).ti,ab. 

65. (genetic adj2 (risk adj3 (assessment or evaluation))).ti,ab. 

66. genogram$.ti,ab. 

67. ((famil$ or heredi$ or inherit$) adj3 (cancer$ or carcinom$ or neoplasm$)).ti,ab. 

68. (genetic adj2 (screening or test$)).ti,ab. 

69. Family Health/ 

70. or/60-69 

71. exp Neoplasms/ 

72. (neoplasm? or carcinoma? or cancer?).ti. 

73. 71 or 72 

74. guideline.pt. 

75. practice guideline.pt. 

76. guideline?.ti. 

77. or/74-76 

78. 70 and 73 and 77 

79. 47 and 58 and 77 

80. 78 or 79 

81. (note or comment or editorial).pt. 

82. 80 not 81 

83. limit 82 to yr="2003 - 2008" 

84. 41 or 83 

A-8
Question 2 

Ovid-MEDLINE 

1. exp Diet Therapy/ or exp Nutrition Physiology/ or exp Nutritional Sciences/ 

2. (diet or diets or dietetic or dietary or eating or intake or nutrient$ or nutrition or vegetarian$ 

or vegan$ or "seventh day adventist" or macrobiotic or breastfeed$ or breast feed$ or 

breastfed or breast fed or breastmilk or breast milk).ti,ab. 

3. exp "food and beverages"/ 

4. (food$ or cereal$ or grain$ or granary or wholegrain or wholewheat or roots or plantain$ or 

tuber or tubers or vegetable$ or fruit$ or pulses or beans or lentils or chickpeas or legume$ or 

soy or soya or nut or nuts or peanut$ or groundnut$ or seeds or meat or beef or pork or lamb 

or poultry or chicken or turkey or duck or fish or fat or fats or fatty or egg or eggs or bread or 

oils or shellfish or seafood or sugar or syrup or dairy or milk or herbs or spices or chilli or 

chillis or pepper$ or condiments).ti,ab. 

5. (fluid intake or water or drinks or drinking or tea or coffee or caffeine or juice or beer or 

spirits or liquor or wine or alcohol or alcoholic or beverage$ or ethanol or yerba mate or ilex 

paraguariensis).ti,ab. 

6. fertilizers/ or exp pesticides/ or Veterinary Drugs/ 

7. (pesticide$ or herbicide$ or DDT or fertiliser$ or fertilizer$ or organic or contaminants or 

contaminate$ or veterinary drug$ or polychlorinated dibenzofuran$ or PCDF$ or 

polychlorinated dibenzodioxin$ or PCDD$ or polychlorinated biphenyl$ or PCB$ or 

cadmium or arsenic or chlorinated hydrocarbon$ or microbial contamination$).ti,ab. 

8. exp Food Preservation/ 

9. (mycotoxin$ or aflatoxin$ or pickled or bottled or bottling or canned or canning or vacuum 

pack$ or refrigerate$ or refrigeration or cured or smoked or preserved or preservatives or 

nitrosamine or hydrogenation or fortified or additive$ or colouring$ or coloring$ or 

flavouring$ or flavoring$ or nitrates or nitrites or solvent or solvents or ferment$ or 

processed or antioxidant$ or genetic modif$ or genetically modif$ or vinyl chloride or 

packaging or labelling or phthalates).ti,ab. 

10. Cookery/ 

11. (cooking or cooked or grill or grilled or fried or fry or roast or bake or baked or stewing or 

stewed or casserol$ or broil or broiled or boiled or microwave or microwaved or re-heating 

or reheating or heating or re-heated or heated or poach or poached or steamed or barbecue$ 

or chargrill$ or heterocyclic amines or polycyclic aromatic hydrocarbons).ti,ab. 

12. exp Dietary Carbohydrates/ or exp Dietary Proteins/ or exp Sweetening Agents/ 

13. (salt or salting or salted or fiber or fibre or polysaccharide$ or starch or starchy or 

carbohydrate$ or lipid$ or linoleic acid$ or sterols or stanols or sugar$ or sweetener$ or 

saccharin$ or aspartame or acesulfame or cyclamates or maltose or mannitol or sorbitol or 

sucrose or xylitol or cholesterol or protein or proteins or hydrogenated dietary oils or 

hydrogenated lard or hydrogenated oils).ti,ab. 

14. exp Vitamins/ 

15. (supplements or supplement or vitamin$ or retinol or carotenoid$ or tocopherol or folate$ or 

folic acid or methionine or riboflavin or thiamine or niacin or pyridoxine or cobalamin or 

mineral$ or sodium or iron or calcium or selenium or iodine or magnesium or potassium or 

zinc or copper or phosphorus or manganese or chromium or phytochemical or allium or 

A-9
isothiocyanate$ or glucosinolate$ or indoles or polyphenol$ or phytoestrogen$ or genistein 

or saponin$ or coumarin$).ti,ab. 

16. Physical Fitness/ or exp Exertion/ or exp Physical Endurance/ or Walking/ 

17. (recreational activit$ or household activit$ or occupational activit$ or physical activit$ or 

physical inactivit$ or exercise or exercising or energy intake or energy expenditure or energy 

balance or energy density).ti,ab. 

18. exp Growth/ or exp Anthropometry/ or exp Body Composition/ or exp Body Constitution/ 

19. (weight loss or weight gain or anthropometry or birth weight or birthweight or birth-weight 

or child development or height or body composition or body mass or BMI or obesity or obese 

or overweight or over-weight or over weight or skinfold measurement$ or skinfold thickness 

or DEXA or bio-impedence or waist circumference or hip circumference or waist hip 

ratio$).ti,ab. 

20. or/1-19 

21. animals/ not (humans/ and animals/) 

22. 20 not 21 

23. meta-analysis.pt,ti,ab,sh. 

24. (meta anal$ or metaanal$).ti,ab,sh. 

25. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ti,ab,sh. 

26. (medline or embase or index medicus).ti,ab. 

27. ((pool$ or combined or combining) adj (data or trials or studies or results)).ti,ab. 

28. 25 or 26 or 27 

29. review.pt,sh. 

30. 28 and 29 

31. 23 or 24 

32. 30 or 31 

33. exp Neoplasms/pc [Prevention & Control] 

34. ((cancer or carcinoma$ or neoplasm$) adj3 (prevent$ or reduc$)).tw. 

35. Breast Neoplasms/ 

36. exp Colorectal Neoplasms/ 

37. exp Ovarian Neoplasms/ 

38. exp Prostatic Neoplasms/ 

39. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

40. or/33-39 

41. 22 and 32 and 40 

42. limit 41 to english language 

43. limit 42 to ed=20060101-20080425 

Ovid-Medline 

1. Mass Screening/ 

2. Smoking Cessation/ 

3. Alcohol Drinking/ 

4. Chemoprevention/ 

5. chemoprevention.ti. 

6. (surveillance or screening).ti. 

7. Primary Prevention/ 

A-10
8. Preventive Medicine/ 

9. Preventive Health Services/ 

10. (prophylactic or preventive or risk reduc$).ti. 

11. risk reduction behavior/ 

12. "Referral and Consultation"/ 

13. medical consultation.ti. 

14. (health adj3 consultation).ti. 

15. or/1-14 

16. Breast Neoplasms/ 

17. exp Colorectal Neoplasms/ 

18. exp Prostatic Neoplasms/ 

19. exp Ovarian Neoplasms/ 

20. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or 

carcinom$)).ti,ab. 

21. or/16-20 

22. self exam$.ti. 

23. Breast Self-Examination/ 

24. exp Mammography/ 

25. mammog$.ti. 

26. Ovariectomy/ 

27. risk reduction mastectomy.ti. 

28. ((prophylactic or preventive or risk reduc$) adj3 (mastectomy or oophorectomy or 

ovariectomy)).tw. 

29. ((magnetic resonance imaging or mri) adj3 breast).ti. 

30. breast exam$.ti. 

31. (ovarian adj3 screening).ti. 

32. exp Contraceptives, Oral/ 

33. tamoxifen/ or raloxifene/ or toremifene/ 

34. (tamoxifen or raloxifene or toremifene or fareston).ti. 

35. or/22-34 

36. Breast Neoplasms/ 

37. (breast adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

38. exp Ovarian Neoplasms/ 

39. (ovar$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

40. or/36-39 

41. 35 and 40 

42. Fenretinide/ 

43. Finasteride/ 

44. (Fenretinide or Finasteride or proscar).ti. 

45. Digital Rectal Examination/ 

46. Toremifene/ 

47. fareston.ti. 

48. (avodart or dutasteride).ti. 

49. Prostate-Specific Antigen/ 

50. (psa adj3 test$).ti. 

51. prostate specific antigen.ti. 

A-11
52. or/42-51 

53. exp Prostatic Neoplasms/ 

54. (prostat$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

55. or/53-54 

56. 52 and 55 

57. Digital Rectal Examination/ 

58. f?ecal occult blood test$.ti. 

59. (FOBT or fob test$).ti. 

60. colonoscopy/ or sigmoidoscopy/ 

61. (sigmoidoscopy or colonoscopy).ti. 

62. Hormone Replacement Therapy/ 

63. hrt.ti. 

64. exp Anti-Inflammatory Agents, Non-Steroidal/ 

65. NSAID?.ti. 

66. (nonsteroidal adj3 inflammatory).ti. 

67. exp Hydroxymethylglutaryl-CoA Reductase Inhibitors/ 

68. HMG-CoA reductase inhibitors.ti. 

69. statins.ti. 

70. or/57-69 

71. exp Colorectal Neoplasms/ 

72. ((colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$)).ti,ab. 

73. or/71-72 

74. 70 and 73 

75. genetic services/ or genetic counseling/ or genetic screening/ 

76. 21 and 75 

77. 15 and 21 

78. 41 or 56 or 74 or 76 or 77 

79. meta-analysis.pt,ti,ab,sh. 

80. (meta anal$ or metaanal$).ti,ab,sh. 

81. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ti. 

82. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ab. 

83. (medline or embase or index medicus).ti,ab. 

84. ((pool$ or combined or combining) adj (data or trials or studies or results)).ti,ab. 

85. or/82-84 

86. review.pt,sh. 

87. 85 and 86 

88. 79 or 80 or 81 or 87 

89. 78 and 88 

90. limit 89 to english language 

91. limit 90 to yr="2000 - 2008" 

92. limit 90 to yr="2003 - 2008" 

A-12
Ovid-EMBASE 

1. exp nutrition/ 

2. (diet or diets or dietetic or dietary or eating or intake or nutrient$ or nutrition or vegetarian$ 

or vegan$ or "seventh day adventist" or macrobiotic or breastfeed$ or breast feed$ or 

breastfed or breast fed or breastmilk or breast milk).ti,ab. 

3. (food$ or cereal$ or grain$ or granary or wholegrain or wholewheat or roots or plantain$ or 

tuber or tubers or vegetable$ or fruit$ or pulses or beans or lentils or chickpeas or legume$ or 

soy or soya or nut or nuts or peanut$ or groundnut$ or seeds or meat or beef or pork or lamb 

or poultry or chicken or turkey or duck or fish or fat or fats or fatty or egg or eggs or bread or 

oils or shellfish or seafood or sugar or syrup or dairy or milk or herbs or spices or chilli or 

chillis or pepper$ or condiments).ti,ab. 

4. (fluid intake or water or drinks or drinking or tea or coffee or caffeine or juice or beer or 

spirits or liquor or wine or alcohol or alcoholic or beverage$ or ethanol or yerba mate or ilex 

paraguariensis).ti,ab. 

5. exp Fertilizer/ 

6. exp Pesticide/ 

7. Veterinary Drug/ 

8. (pesticide$ or herbicide$ or DDT or fertiliser$ or fertilizer$ or organic or contaminants or 

contaminate$ or veterinary drug$ or polychlorinated dibenzofuran$ or PCDF$ or 

polychlorinated dibenzodioxin$ or PCDD$ or polychlorinated biphenyl$ or PCB$ or 

cadmium or arsenic or chlorinated hydrocarbon$ or microbial contamination$).ti,ab. 

9. exp food preservation/ 

10. (mycotoxin$ or aflatoxin$ or pickled or bottled or bottling or canned or canning or vacuum 

pack$ or refrigerate$ or refrigeration or cured or smoked or preserved or preservatives or 

nitrosamine or hydrogenation or fortified or additive$ or colouring$ or coloring$ or 

flavouring$ or flavoring$ or nitrates or nitrites or solvent or solvents or ferment$ or 

processed or antioxidant$ or genetic modif$ or genetically modif$ or vinyl chloride or 

packaging or labelling or phthalates).ti,ab. 

11. cooking/ 

12. (cooking or cooked or grill or grilled or fried or fry or roast or bake or baked or stewing or 

stewed or casserol$ or broil or broiled or boiled or microwave or microwaved or re-heating 

or reheating or heating or re-heated or heated or poach or poached or steamed or barbecue$ 

or chargrill$ or heterocyclic amines or polycyclic aromatic hydrocarbons).ti,ab. 

13. *Carbohydrate/ 

14. exp "peptides and proteins"/ or protein/ 

15. (salt or salting or salted or fiber or fibre or polysaccharide$ or starch or starchy or 

carbohydrate$ or lipid$ or linoleic acid$ or sterols or stanols or sugar$ or sweetener$ or 

saccharin$ or aspartame or acesulfame or cyclamates or maltose or mannitol or sorbitol or 

sucrose or xylitol or cholesterol or protein or proteins or hydrogenated dietary oils or 

hydrogenated lard or hydrogenated oils).ti,ab. 

16. exp Vitamin/ 

17. (supplements or supplement or vitamin$ or retinol or carotenoid$ or tocopherol or folate$ or 

folic acid or methionine or riboflavin or thiamine or niacin or pyridoxine or cobalamin or 

mineral$ or sodium or iron or calcium or selenium or iodine or magnesium or potassium or 

zinc or copper or phosphorus or manganese or chromium or phytochemical or allium or 

A-13
isothiocyanate$ or glucosinolate$ or indoles or polyphenol$ or phytoestrogen$ or genistein 

or saponin$ or coumarin$).ti,ab. 

18. exp "physical activity, capacity and performance"/ 

19. (recreational activit$ or household activit$ or occupational activit$ or physical activit$ or 

physical inactivit$ or exercise or exercising or energy intake or energy expenditure or energy 

balance or energy density).ti,ab. 

20. growth/ or exp body growth/ 

21. anthropometry/ 

22. exp body composition/ 

23. body constitution/ 

24. (weight loss or weight gain or anthropometry or birth weight or birthweight or birth-weight 

or child development or height or body composition or body mass or BMI or obesity or obese 

or overweight or over-weight or over weight or skinfold measurement$ or skinfold thickness 

or DEXA or bio-impedence or waist circumference or hip circumference or waist hip 

ratio$).ti,ab. 

25. or/1-24 

26. meta-analysis.ti,ab,sh. 

27. (meta anal$ or metaanal$).ti,ab,sh. 

28. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ti,ab,sh. 

29. (medline or embase or index medicus).ti,ab. 

30. ((pool$ or combined or combining) adj (data or trials or studies or results)).ti,ab. 

31. 28 or 29 or 30 

32. review.pt,sh. 

33. 31 and 32 

34. 26 or 27 or 33 

35. exp Breast Cancer/ 

36. exp Colon Cancer/ 

37. exp Ovary Cancer/ 

38. exp Prostate Cancer/ 

39. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

40. exp Neoplasm/pc [Prevention] 

41. cancer prevention/ 

42. ((cancer or carcinoma$ or neoplasm$ or tumo?r$) adj3 (prevent$ or reduc$)).tw. 

43. or/35-42 

44. 25 and 34 and 43 

45. limit 44 to english language 

46. animal/ not (human/ and animal/) 

47. 45 not 46 

48. limit 47 to em=200601-200817 

Ovid-EMBASE 

1. cancer screening/ 

2. genetic services/ or genetic counseling/ or genetic screening/ 

3. prophylaxis/ or breast care/ or cancer prevention/ or chemoprophylaxis/ or periodic medical 

examination/ or personal monitoring/ or secondary prevention/ or smoking cessation/ 

A-14
4. alcohol abstinence/ or behavioral risk factor surveillance system/ or drinking behavior/ or 

risk reduction/ 

5. (chemoprevention or chemoprophylaxis).ti. 

6. (surveillance or screening).ti. 

7. disease surveillance/ 

8. PREVENTIVE HEALTH SERVICE/ or PREVENTIVE MEDICINE/ 

9. (prophylactic or preventive or risk reduc$).ti. 

10. patient referral/ 

11. medical consultation.ti. 

12. (health adj3 consultation).ti. 

13. or/1-12 

14. exp Breast Cancer/ 

15. exp Colon Cancer/ 

16. exp Ovary Cancer/ 

17. exp Prostate Cancer/ 

18. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

19. or/14-18 

20. exp breast examination/ 

21. self exam$.ti. 

22. Ovariectomy/ 

23. exp mastectomy/ 

24. mammog$.ti. 

25. ((prophylactic or preventive or risk reduc$) adj3 (mastectomy or oophorectomy or 

ovariectomy)).tw. 

26. ((magnetic resonance imaging or mri) adj3 breast).ti. 

27. breast exam$.ti. 

28. (ovarian adj3 screening).ti. 

29. exp Oral Contraceptive Agent/ 

30. raloxifene/ or tamoxifen/ or toremifene/ 

31. (tamoxifen or raloxifene or toremifene or fareston).ti. 

32. or/20-31 

33. exp Breast Cancer/ 

34. (breast adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

35. exp Ovary Cancer/ 

36. (ovar$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

37. or/33-36 

38. 32 and 37 

39. Fenretinide/ 

40. Finasteride/ 

41. (Fenretinide or Finasteride or proscar).ti. 

42. digital rectal examination/ 

43. Toremifene/ 

44. fareston.ti. 

45. (avodart or dutasteride).ti. 

46. Prostate Specific Antigen/ 

A-15
47. (psa adj3 test$).ti. 

48. prostate specific antigen.ti. 

49. or/39-48 

50. exp Prostate Cancer/ 

51. (prostat$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

52. or/50-51 

53. 49 and 52 

54. digital rectal examination/ 

55. f?ecal occult blood test$.ti. 

56. (FOBT or fob test$).ti. 

57. colonoscopy/ or sigmoidoscopy/ 

58. hormone replacement therapy.ti. 

59. hrt.ti. 

60. exp Hormone Substitution/ 

61. exp Nonsteroid Antiinflammatory Agent/ 

62. NSAID?.ti. 

63. (nonsteroidal adj3 inflammatory).ti. 

64. exp Hydroxymethylglutaryl Coenzyme a Reductase Inhibitor/ 

65. HMG-CoA reductase inhibitors.ti. 

66. statins.ti. 

67. or/54-66 

68. exp Colon Cancer/ 

69. ((colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$)).ti,ab. 

70. or/68-69 

71. 67 and 70 

72. 13 and 19 

73. 38 or 53 or 71 or 72 

74. meta analysis/ 

75. meta-analysis.ti,ab. 

76. (meta anal$ or metaanal$).ti,ab. 

77. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ti. 

78. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ab. 

79. (medline or embase or index medicus).ti,ab. 

80. ((pool$ or combined or combining) adj (data or trials or studies or results)).ti,ab. 

81. or/78-80 

82. review.pt,sh. 

83. 81 and 82 

84. or/74-77 

85. 83 or 84 

86. 73 and 85 

87. limit 86 to english language 

88. limit 87 to yr="2000 - 2008" 

89. limit 87 to yr="2003 - 2008" 

A-16
Ovid-CINAHL 

1. Diet Therapy/ 

2. exp Nutrition/ 

3. (diet or diets or dietetic or dietary or eating or intake or nutrient$ or nutrition or vegetarian$ 

or vegan$ or "seventh day adventist" or macrobiotic or breastfeed$ or breast feed$ or 

breastfed or breast fed or breastmilk or breast milk).ti,ab. 

4. exp "food and beverages"/ or food/ 

5. (food$ or cereal$ or grain$ or granary or wholegrain or wholewheat or roots or plantain$ or 

tuber or tubers or vegetable$ or fruit$ or pulses or beans or lentils or chickpeas or legume$ or 

soy or soya or nut or nuts or peanut$ or groundnut$ or seeds or meat or beef or pork or lamb 

or poultry or chicken or turkey or duck or fish or fat or fats or fatty or egg or eggs or bread or 

oils or shellfish or seafood or sugar or syrup or dairy or milk or herbs or spices or chilli or 

chillis or pepper$ or condiments).ti,ab. 

6. (fluid intake or water or drinks or drinking or tea or coffee or caffeine or juice or beer or 

spirits or liquor or wine or alcohol or alcoholic or beverage$ or ethanol or yerba mate or ilex 

paraguariensis).ti,ab. 

7. exp Pesticides/ 

8. Veterinary Medicine/ 

9. (pesticide$ or herbicide$ or DDT or fertiliser$ or fertilizer$ or organic or contaminants or 

contaminate$ or veterinary drug$ or polychlorinated dibenzofuran$ or PCDF$ or 

polychlorinated dibenzodioxin$ or PCDD$ or polychlorinated biphenyl$ or PCB$ or 

cadmium or arsenic or chlorinated hydrocarbon$ or microbial contamination$).ti,ab. 

10. exp Food Preservation/ 

11. (mycotoxin$ or aflatoxin$ or pickled or bottled or bottling or canned or canning or vacuum 

pack$ or refrigerate$ or refrigeration or cured or smoked or preserved or preservatives or 

nitrosamine or hydrogenation or fortified or additive$ or colouring$ or coloring$ or 

flavouring$ or flavoring$ or nitrates or nitrites or solvent or solvents or ferment$ or 

processed or antioxidant$ or genetic modif$ or genetically modif$ or vinyl chloride or 

packaging or labelling or phthalates).ti,ab. 

12. Cooking/ 

13. (cooking or cooked or grill or grilled or fried or fry or roast or bake or baked or stewing or 

stewed or casserol$ or broil or broiled or boiled or microwave or microwaved or re-heating 

or reheating or heating or re-heated or heated or poach or poached or steamed or barbecue$ 

or chargrill$ or heterocyclic amines or polycyclic aromatic hydrocarbons).ti,ab. 

14. exp Dietary Carbohydrates/ 

15. exp Dietary Proteins/ 

16. exp Sweetening Agents/ 

17. (salt or salting or salted or fiber or fibre or polysaccharide$ or starch or starchy or 

carbohydrate$ or lipid$ or linoleic acid$ or sterols or stanols or sugar$ or sweetener$ or 

saccharin$ or aspartame or acesulfame or cyclamates or maltose or mannitol or sorbitol or 

sucrose or xylitol or cholesterol or protein or proteins or hydrogenated dietary oils or 

hydrogenated lard or hydrogenated oils).ti,ab. 

18. exp Vitamins/ 

19. (supplements or supplement or vitamin$ or retinol or carotenoid$ or tocopherol or folate$ or 

folic acid or methionine or riboflavin or thiamine or niacin or pyridoxine or cobalamin or 

mineral$ or sodium or iron or calcium or selenium or iodine or magnesium or potassium or 

A-17
zinc or copper or phosphorus or manganese or chromium or phytochemical or allium or 

isothiocyanate$ or glucosinolate$ or indoles or polyphenol$ or phytoestrogen$ or genistein 

or saponin$ or coumarin$).ti,ab. 

20. Physical Fitness/ 

21. exp Exertion/ 

22. Walking/ 

23. (recreational activit$ or household activit$ or occupational activit$ or physical activit$ or 

physical inactivit$ or exercise or exercising or energy intake or energy expenditure or energy 

balance or energy density).ti,ab. 

24. exp Growth/ 

25. exp "Body Weights and Measures"/ 

26. exp Body Composition/ 

27. exp Body Constitution/ 

28. (weight loss or weight gain or anthropometry or birth weight or birthweight or birth-weight 

or child development or height or body composition or body mass or BMI or obesity or obese 

or overweight or over-weight or over weight or skinfold measurement$ or skinfold thickness 

or DEXA or bio-impedence or waist circumference or hip circumference or waist hip 

ratio$).ti,ab. 

29. or/1-28 

30. meta-analysis.ti,ab,sh. 

31. (meta anal$ or metaanal$).ti,ab,sh. 

32. systematic review.pt. 

33. systematic review.ti. 

34. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ti,ab,sh. 

35. (medline or embase or index medicus).ti,ab. 

36. ((pool$ or combined or combining) adj (data or trials or studies or results)).ti,ab. 

37. 34 or 35 or 36 

38. review.pt,sh. 

39. 37 and 38 

40. 30 or 31 or 32 or 33 

41. 39 or 40 

42. exp Breast Neoplasms/ 

43. exp Colorectal Neoplasms/ 

44. exp Ovarian Neoplasms/ 

45. exp Prostatic Neoplasms/ 

46. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

47. or/42-46 

48. 29 and 41 and 47 

49. limit 48 to ew=2006$ 

50. limit 48 to ew=2007$ 

51. limit 48 to ew=2008$ 

52. 49 or 50 or 51 

53. limit 52 to english 

A-18
Ovid-CINAHL 

1. cancer screening/ or genetic screening/ 

2. Genetic Counseling/ 

3. Chemoprevention/ 

4. "Referral and Consultation"/ 

5. Smoking Cessation/ 

6. Alcohol Drinking/ 

7. (chemoprevention or chemoprophylaxis).ti. 

8. Disease Surveillance/ 

9. (surveillance or screening).ti. 

10. Preventive Health Care/ 

11. (prophylactic or preventive or risk reduc$).ti. 

12. medical consultation.ti. 

13. (health adj3 consultation).ti. 

14. Risk Management/ 

15. or/1-14 

16. Breast Care/ 

17. breast examination/ or breast self-examination/ 

18. self exam$.ti. 

19. Oophorectomy/ 

20. Mastectomy/ 

21. Mammography/ 

22. mammog$.ti. 

23. ((prophylactic or preventive or risk reduc$) adj3 (mastectomy or oophorectomy or 

ovariectomy)).tw. 

24. ((magnetic resonance imaging or mri) adj3 breast).ti. 

25. breast exam$.ti. 

26. (ovarian adj3 screening).ti. 

27. exp Contraceptives, Oral/ 

28. raloxifene/ or tamoxifen/ 

29. (tamoxifen or raloxifene or toremifene or fareston).ti. 

30. or/16-29 

31. exp Breast Neoplasms/ 

32. exp Ovarian Neoplasms/ 

33. (breast adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

34. (ovar$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

35. or/31-34 

36. 30 and 35 

37. Finasteride/ 

38. (Fenretinide or Finasteride or proscar).ti. 

39. Digital Rectal Examination/ 

40. Toremifene.ti. 

41. fareston.ti. 

42. (avodart or dutasteride).ti. 

43. Prostate-Specific Antigen/ 

44. (psa adj3 test$).ti. 

A-19
45. prostate specific antigen.ti. 

46. or/37-45 

47. exp Prostatic Neoplasms/ 

48. (prostat$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

49. or/47-48 

50. 46 and 49 

51. Digital Rectal Examination/ 

52. f?ecal occult blood test$.ti. 

53. (FOBT or fob test$).ti. 

54. colonoscopy/ or sigmoidoscopy/ 

55. Hormone Replacement Therapy/ 

56. hormone replacement therapy.ti. 

57. hrt.ti. 

58. exp Antiinflammatory Agents, Non-Steroidal/ 

59. NSAID?.ti. 

60. (nonsteroidal adj3 inflammatory).ti. 

61. exp Statins/ 

62. HMG-CoA reductase inhibitors.ti. 

63. statins.ti. 

64. or/51-63 

65. exp Colorectal Neoplasms/ 

66. ((colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

67. or/65-66 

68. 64 and 67 

69. exp Breast Neoplasms/ 

70. exp Colorectal Neoplasms/ 

71. exp Prostatic Neoplasms/ 

72. exp Ovarian Neoplasms/ 

73. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti. 

74. or/69-73 

75. 15 and 74 

76. 36 or 50 or 68 or 75 

77. Meta Analysis/ 

78. (meta anal$ or metaanal$).ti,ab. 

79. meta-analysis.ti,ab. 

80. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ti. 

81. ((methodol$ or systematic$ or quantitativ$) adj3 (review$ or overview$ or survey$)).ab. 

82. (medline or embase or index medicus).ti,ab. 

83. ((pool$ or combined or combining) adj (data or trials or studies or results)).ti,ab. 

84. or/81-83 

85. review.pt,sh. 

86. 84 and 85 

87. "Systematic Review"/ 

88. systematic review.pt. 

89. 78 or 79 or 80 or 86 or 87 or 88 

A-20
90. 76 and 89 

91. limit 90 to english 

92. limit 91 to yr="2000 - 2008" 

93. limit 91 to yr="2003 - 2008 

Ovid-CDSR 

1. (diet or diets or dietetic or dietary or eating or intake or nutrient$ or nutrition or vegetarian$ 

or vegan$ or "seventh day adventist" or macrobiotic or breastfeed$ or breast feed$ or 

breastfed or breast fed or breastmilk or breast milk).ti,ab. 

2. (food$ or cereal$ or grain$ or granary or wholegrain or wholewheat or roots or plantain$ or 

tuber or tubers or vegetable$ or fruit$ or pulses or beans or lentils or chickpeas or legume$ or 

soy or soya or nut or nuts or peanut$ or groundnut$ or seeds or meat or beef or pork or lamb 

or poultry or chicken or turkey or duck or fish or fat or fats or fatty or egg or eggs or bread or 

oils or shellfish or seafood or sugar or syrup or dairy or milk or herbs or spices or chilli or 

chillis or pepper$ or condiments).ti,ab. 

3. (fluid intake or water or drinks or drinking or tea or coffee or caffeine or juice or beer or 

spirits or liquor or wine or alcohol or alcoholic or beverage$ or ethanol or yerba mate or ilex 

paraguariensis).ti,ab. 

4. (pesticide$ or herbicide$ or DDT or fertiliser$ or fertilizer$ or organic or contaminants or 

contaminate$ or veterinary drug$ or polychlorinated dibenzofuran$ or PCDF$ or 

polychlorinated dibenzodioxin$ or PCDD$ or polychlorinated biphenyl$ or PCB$ or 

cadmium or arsenic or chlorinated hydrocarbon$ or microbial contamination$).ti,ab. 

5. (mycotoxin$ or aflatoxin$ or pickled or bottled or bottling or canned or canning or vacuum 

pack$ or refrigerate$ or refrigeration or cured or smoked or preserved or preservatives or 

nitrosamine or hydrogenation or fortified or additive$ or colouring$ or coloring$ or 

flavouring$ or flavoring$ or nitrates or nitrites or solvent or solvents or ferment$ or 

processed or antioxidant$ or genetic modif$ or genetically modif$ or vinyl chloride or 

packaging or labelling or phthalates).ti,ab. 

6. (cooking or cooked or grill or grilled or fried or fry or roast or bake or baked or stewing or 

stewed or casserol$ or broil or broiled or boiled or microwave or microwaved or re-heating 

or reheating or heating or re-heated or heated or poach or poached or steamed or barbecue$ 

or chargrill$ or heterocyclic amines or polycyclic aromatic hydrocarbons).ti,ab. 

7. (salt or salting or salted or fiber or fibre or polysaccharide$ or starch or starchy or 

carbohydrate$ or lipid$ or linoleic acid$ or sterols or stanols or sugar$ or sweetener$ or 

saccharin$ or aspartame or acesulfame or cyclamates or maltose or mannitol or sorbitol or 

sucrose or xylitol or cholesterol or protein or proteins or hydrogenated dietary oils or 

hydrogenated lard or hydrogenated oils).ti,ab. 

8. (supplements or supplement or vitamin$ or retinol or carotenoid$ or tocopherol or folate$ or 

folic acid or methionine or riboflavin or thiamine or niacin or pyridoxine or cobalamin or 

mineral$ or sodium or iron or calcium or selenium or iodine or magnesium or potassium or 

zinc or copper or phosphorus or manganese or chromium or phytochemical or allium or 

isothiocyanate$ or glucosinolate$ or indoles or polyphenol$ or phytoestrogen$ or genistein 

or saponin$ or coumarin$).ti,ab. 

9. (recreational activit$ or household activit$ or occupational activit$ or physical activit$ or 

physical inactivit$ or exercise or exercising or energy intake or energy expenditure or energy 

balance or energy density).ti,ab. 

A-21
10. (weight loss or weight gain or anthropometry or birth weight or birthweight or birth-weight 

or child development or height or body composition or body mass or BMI or obesity or obese 

or overweight or over-weight or over weight or skinfold measurement$ or skinfold thickness 

or DEXA or bio-impedence or waist circumference or hip circumference or waist hip 

ratio$).ti,ab. 

11. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

12. or/1-10 

13. 11 and 12 

Ovid-CDSR 

1. chemoprevention.ti. 

2. (surveillance or screening).ti. 

3. (prophylactic or preventive or risk reduc$).ti. 

4. medical consultation.ti. 

5. (health adj3 consultation).ti. 

6. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or 

carcinom$)).ti,ab. 

7. self exam$.ti. 

8. mammog$.ti. 

9. risk reduction mastectomy.ti. 

10. ((prophylactic or preventive or risk reduc$) adj3 (mastectomy or oophorectomy or 

ovariectomy)).tw. 

11. ((magnetic resonance imaging or mri) adj3 breast).ti. 

12. breast exam$.ti. 

13. (ovarian adj3 screening).ti. 

14. (tamoxifen or raloxifene or toremifene or fareston).ti. 

15. (breast adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

16. (ovar$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

17. (Fenretinide or Finasteride or proscar).ti. 

18. fareston.ti. 

19. (avodart or dutasteride).ti. 

20. (psa adj3 test$).ti. 

21. prostate specific antigen.ti. 

22. (prostat$ adj3 (cancer$ or neoplasm$ or carcinom$)).ti. 

23. f?ecal occult blood test$.ti. 

24. (FOBT or fob test$).ti. 

25. hrt.ti. 

26. NSAID?.ti. 

27. (nonsteroidal adj3 inflammatory).ti. 

28. HMG-CoA reductase inhibitors.ti. 

29. statins.ti. 

30. ((colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$)).ti,ab. 

31. or/1-5 

32. or/7-14 

33. or/15-16 

A-22
34. or/17-21 

35. or/23-29 

36. 6 and 31 

37. 33 and 32 

38. 22 and 34 

39. 35 and 30 

40. or/36-39 

A-23
Question 3 

Ovid-Medline 

1. family history.ab. 

2. Genetic Predisposition to Disease/ 

3. BRCA$.ti. 

4. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

5. exp Genetic Services/ 

6. genes, brca1/ or genes, brca2/ 

7. or/1-6 

8. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

9. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

10. *Neoplasms/ 

11. or/8-10 

12. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (factors or behavio?r$ or intention or increase or change or impact)).ti. 

13. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (mammography or test$ or screen$ or exercise or physical activity or diet or food 

or smoking or alcohol or utili?ation or "use")).ti. 

14. ((factors or behavio?r$ or intention or increase or change or impact or risk) adj8 

(mammography or test$ or screen$ or exercise or physical activity or diet or food or smoking 

or alcohol or utili?ation or "use")).ti. 

15. (uptake or motivation or compliance or adherence or seeking or practices or patterns).ti. 

16. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (change? or impact? or modification? or influence or risk)).ti. 

17. ((after or following or "because of" or "due to" or "result of") adj9 (genetic test$ or genetic 

counsel?ing or genetic screening)).ti. 

18. ((after or following or "because of" or "due to" or "result of") adj9 (mutation test$ or 

mutation screen$)).ti. 

19. exp Health Behavior/ 

20. risk reduction behavior/ 

21. or/12-20 

22. 7 and 11 and 21 

23. animals/ not (humans/ and animals/) 

24. 22 not 23 

25. limit 24 to english language 

26. (note or comment or editorial).pt. 

27. 25 not 26 

28. limit 27 to yr="1990 - 2008" 

A-24
Ovid-EMBASE 

1. exp health behavior/ 

2. behavior change/ 

3. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (factors or behavio?r$ or intention or increase or change or impact)).ti. 

4. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (mammography or test$ or screen$ or exercise or physical activity or diet or food 

or smoking or alcohol or utili?ation or "use")).ti. 

5. ((factors or behavio?r$ or intention or increase or change or impact or risk) adj8 

(mammography or test$ or screen$ or exercise or physical activity or diet or food or smoking 

or alcohol or utili?ation or "use")).ti. 

6. (uptake or motivation or compliance or adherence or seeking or practices or patterns).ti. 

7. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (change? or impact? or modification? or influence or risk)).ti. 

8. ((after or following or "because of" or "due to" or "result of") adj9 (genetic test$ or genetic 

counsel?ing or genetic screening)).ti. 

9. ((after or following or "because of" or "due to" or "result of") adj9 (mutation test$ or 

mutation screen$)).ti. 

10. or/1-9 

11. Familial Cancer/ 

12. exp Breast Cancer/ 

13. exp Colon Cancer/ 

14. exp Ovary Cancer/ 

15. exp Prostate Cancer/ 

16. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

17. *Cancer/ 

18. or/11-17 

19. genetic predisposition/ or genetic susceptibility/ 

20. family history/ 

21. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

22. exp genetic service/ 

23. brca1 protein/ or brca2 protein/ 

24. family history.ab. 

25. Familial Cancer/ 

26. BRCA$.ti. 

27. or/19-26 

28. 10 and 18 and 27 

29. limit 28 to human 

30. limit 29 to english language 

31. (note or editorial).pt. 

32. 30 not 31 

33. limit 32 to yr="1990 - 2008" 

A-25
Ovid-CCRT 

1. family history.ab. 

2. Genetic Predisposition to Disease/ 

3. BRCA$.ti. 

4. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

5. exp Genetic Services/ 

6. genes, brca1/ or genes, brca2/ 

7. or/1-6 

8. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

9. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

10. *Neoplasms/ 

11. or/8-10 

12. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (factors or behavio?r$ or intention or increase or change or impact)).ti. 

13. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (mammography or test$ or screen$ or exercise or physical activity or diet or food 

or smoking or alcohol or utili?ation or "use")).ti. 

14. ((factors or behavio?r$ or intention or increase or change or impact or risk) adj8 

(mammography or test$ or screen$ or exercise or physical activity or diet or food or smoking 

or alcohol or utili?ation or "use")).ti. 

15. (uptake or motivation or compliance or adherence or seeking or practices or patterns).ti. 

16. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (change? or impact? or modification? or influence or risk)).ti. 

17. ((after or following or "because of" or "due to" or "result of") adj9 (genetic test$ or genetic 

counsel?ing or genetic screening)).ti. 

18. ((after or following or "because of" or "due to" or "result of") adj9 (mutation test$ or 

mutation screen$)).ti. 

19. exp Health Behavior/ 

20. risk reduction behavior/ 

21. or/12-20 

22. 7 and 11 and 21 

23. limit 22 to yr="1990 - 2008" 

Ovid-CINAHL 

1. health behavior/ or patient compliance/ or medication compliance/ or treatment refusal/ or 

help seeking behavior/ 

2. Behavioral Changes/ 

3. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (factors or behavio?r$ or intention or increase or change or impact)).ti. 

4. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (mammography or test$ or screen$ or exercise or physical activity or diet or food 

or smoking or alcohol or utili?ation or "use")).ti. 

A-26
5. ((factors or behavio?r$ or intention or increase or change or impact or risk) adj8 

(mammography or test$ or screen$ or exercise or physical activity or diet or food or smoking 

or alcohol or utili?ation or "use")).ti. 

6. (uptake or motivation or compliance or adherence or seeking or practices or patterns).ti. 

7. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (change? or impact? or modification? or influence or risk)).ti. 

8. ((after or following or "because of" or "due to" or "result of") adj9 (genetic test$ or genetic 

counsel?ing or genetic screening)).ti. 

9. ((after or following or "because of" or "due to" or "result of") adj9 (mutation test$ or 

mutation screen$)).ti. 

10. attitude to change/ or attitude to risk/ 

11. or/1-10 

12. exp Breast Neoplasms/ 

13. exp Colorectal Neoplasms/ 

14. exp Ovarian Neoplasms/ 

15. exp Prostatic Neoplasms/ 

16. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

17. *Neoplasms/pc [Prevention and Control] 

18. or/12-17 

19. Genetic Screening/ or Genetic Counseling/ 

20. Family History/ 

21. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

22. Genes, BRCA/ 

23. family history.ab. 

24. BRCA$.ti. 

25. or/19-24 

26. 11 and 18 and 25 

27. limit 26 to english 

28. limit 27 to yr="1990 - 2008" 

Ovid-PsycINFO 

1. health behavior/ 

2. lifestyle changes/ or behavior change/ or health promotion/ or readiness to change/ 

3. preventive medicine/ or health promotion/ 

4. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (factors or behavio?r$ or intention or increase or change or impact)).ti. 

5. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (mammography or test$ or screen$ or exercise or physical activity or diet or food 

or smoking or alcohol or utili?ation or "use")).ti. 

6. ((factors or behavio?r$ or intention or increase or change or impact or risk) adj8 

(mammography or test$ or screen$ or exercise or physical activity or diet or food or smoking 

or alcohol or utili?ation or "use")).ti. 

7. (uptake or motivation or compliance or adherence or seeking or practices or patterns).ti. 

A-27
8. ((relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk) adj8 (change? or impact? or modification? or influence or risk)).ti. 

9. ((after or following or "because of" or "due to" or "result of") adj9 (genetic test$ or genetic 

counsel?ing or genetic screening)).ti. 

10. ((after or following or "because of" or "due to" or "result of") adj9 (mutation test$ or 

mutation screen$)).ti. 

11. risk management/ 

12. or/1-11 

13. at risk populations/ or predisposition/ or "susceptibility (disorders)"/ 

14. family history.ab. 

15. genetics/ or mutations/ 

16. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

17. genetic testing/ or genetic counseling/ 

18. BRCA$.ti. 

19. or/13-18 

20. breast neoplasms/ 

21. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

22. *neoplasms/ 

23. or/20-22 

24. 12 and 19 and 23 

25. limit 24 to human 

26. limit 25 to english language 

27. limit 26 to yr="1990 - 2008" 

A-28
Question 4 

Ovid-MEDLINE 

1. family history.ab. 

2. Genetic Predisposition to Disease/ 

3. BRCA$.ti. 

4. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

5. exp Genetic Services/ 

6. genes, brca1/ or genes, brca2/ 

7. or/1-6 

8. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

9. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

10. *Neoplasms/ 

11. or/8-10 

12. anxiety/ or fear/ 

13. depression/ or stress, psychological/ 

14. ((worry or anxiety or depression or distress or coping or fear) and cancer).ti. 

15. ((psychological or psychosocial) and cancer).ti. 

16. (perception and cancer).ti. 

17. (impact and cancer).ti. 

18. family relations/ 

19. ((insurance or employment) and cancer).ti. 

20. insurance/ or exp insurance, health/ 

21. insurance.ti. 

22. (prejudice or discrimination).ti. 

23. (harm? or fatalism).tw. 

24. or/12-23 

25. employment/ or workplace/ 

26. prejudice/ 

27. 24 or 26 

28. 7 and 11 and 27 

29. animals/ not (humans/ and animals/) 

30. 28 not 29 

31. (note or comment or editorial).pt. 

32. 30 not 31 

33. limit 32 to english language 

34. limit 33 to yr="1990 - 2008" 

Ovid-EMBASE 

1. emotional stress/ or family stress/ or interpersonal stress/ 

2. fear/ or anxiety/ 

3. exp Depression/ 

4. ((worry or anxiety or depression or distress or coping or fear) and cancer).ti. 

A-29
5. ((psychological or psychosocial) and cancer).ti. 

6. (perception and cancer).ti. 

7. (impact and cancer).ti. 

8. family relation/ 

9. family stress/ 

10. CANCER FAMILY/ 

11. ((insurance or employment) and cancer).ti. 

12. exp health insurance/ 

13. insurance/ or exp insurance, health/ 

14. (prejudice or discrimination).ti. 

15. (harm? or fatalism).tw. 

16. employment discrimination/ 

17. or/2-16 

18. Familial Cancer/ 

19. exp Breast Cancer/ 

20. exp Colon Cancer/ 

21. exp Ovary Cancer/ 

22. exp Prostate Cancer/ 

23. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

24. *Cancer/ 

25. or/18-24 

26. genetic predisposition/ or genetic susceptibility/ 

27. family history/ 

28. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

29. exp genetic service/ 

30. brca1 protein/ or brca2 protein/ 

31. family history.ab. 

32. Familial Cancer/ 

33. BRCA$.ti. 

34. or/26-33 

35. 17 and 25 and 34 

36. limit 35 to human 

37. (note or comment or editorial).pt. 

38. 36 not 37 

39. limit 38 to english language 

40. limit 39 to yr="1990 - 2008" 

OVID-CCRT 

1. family history.ab. 

2. Genetic Predisposition to Disease/ 

3. BRCA$.ti. 

4. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

5. exp Genetic Services/ 

A-30
6. genes, brca1/ or genes, brca2/ 

7. or/1-6 

8. exp breast neoplasms/ or exp colorectal neoplasms/ or exp ovarian neoplasms/ or exp 

prostatic neoplasms/ 

9. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

10. *Neoplasms/ 

11. or/8-10 

12. anxiety/ or fear/ 

13. depression/ or stress, psychological/ 

14. ((worry or anxiety or depression or distress or coping or fear) and cancer).ti. 

15. ((psychological or psychosocial) and cancer).ti. 

16. (perception and cancer).ti. 

17. (impact and cancer).ti. 

18. family relations/ 

19. ((insurance or employment) and cancer).ti. 

20. insurance/ or exp insurance, health/ 

21. insurance.ti. 

22. (prejudice or discrimination).ti. 

23. (harm? or fatalism).tw. 

24. or/12-23 

25. employment/ or workplace/ 

26. prejudice/ 

27. 24 or 26 

28. 7 and 11 and 27 

29. limit 28 to yr="1990 - 2008" 

Ovid-CINAHL 

1. exp Breast Neoplasms/ 

2. exp Colorectal Neoplasms/ 

3. exp Ovarian Neoplasms/ 

4. exp Prostatic Neoplasms/ 

5. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

6. *Neoplasms/pc [Prevention and Control] 

7. or/1-6 

8. Genetic Screening/ or Genetic Counseling/ 

9. Family History/ 

10. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

11. Genes, BRCA/ 

12. family history.ab. 

13. BRCA$.ti. 

14. or/8-13 

15. exp Coping/ 

16. exp "Psychosocial Aspects of Illness"/ 

A-31
17. stress/ or stress, psychological/ 

18. anxiety/ or depression/ 

19. Fear/ 

20. ((worry or anxiety or depression or distress or coping or fear) and cancer).ti. 

21. ((psychological or psychosocial) and cancer).ti. 

22. (perception and cancer).ti. 

23. (impact and cancer).ti. 

24. family functioning/ or family coping/ or family relations/ 

25. ((insurance or employment) and cancer).ti. 

26. insurance coverage/ or insurance, health/ 

27. Discrimination, Employment/ 

28. (prejudice or discrimination).ti. 

29. (harm? or fatalism).tw. 

30. or/15-29 

31. 7 and 14 and 30 

32. limit 31 to english 

33. limit 32 to yr="1990 - 2008" 

Ovid-PsycINFO 

1. coping behavior/ or hopelessness/ 

2. anxiety/ 

3. psychological stress/ 

4. emotional states/ or "depression (emotion)"/ 

5. fear/ 

6. ((worry or anxiety or depression or distress or coping or fear) and cancer).ti. 

7. ((psychological or psychosocial) and cancer).ti. 

8. (perception and cancer).ti. 

9. (impact and cancer).ti. 

10. distress/ 

11. family relations/ or interpersonal relationships/ 

12. emotional adjustment/ or coping behavior/ 

13. emotional adjustment/ 

14. or/1-13 

15. at risk populations/ or predisposition/ or "susceptibility (disorders)"/ 

16. family history.ab. 

17. genetics/ or mutations/ 

18. (relative? or genetic or heredit$ or famil$ or inherit$ or high$ risk or "at risk" or increased 

risk).ti. 

19. genetic testing/ or genetic counseling/ 

20. BRCA$.ti. 

21. or/15-20 

22. breast neoplasms/ 

23. ((breast or ovar$ or prostate or colon or colorectal) adj3 (cancer$ or neoplasm$ or carcinom$ 

or tumo?r$)).ti,ab. 

24. *neoplasms/ 

25. or/22-24 

A-32
A-33

26. 14 and 21 and 25 

27. limit 26 to human 

28. limit 27 to english language 

29. limit 28 to yr="1990 - 2008" 
Appendix B – Forms and Guides 

Level 1 – Title and Abstract Screening 

Family History II, Screening level 1 

1. Is this article non-English or a commentary, editorial or non-systematic review? 

Yes (Stop) 

No (Continue) 

2. Does the citation include any of the following cancers? 

Breast/Colorectal/Colon/Rectal/Ovarian/Prostate/Cancer in general (Continue) 

None of the above (Stop) 

3. Is this a clinical practice guideline? 

Yes (Stop) 

No (Continue) 

4. Is this a systematic review or meta-analysis? 

Not a systematic review or meta-analysis (Continue) 

A systematic review or meta-analysis that focuses on an intervention to prevent or reduce 

the risk of cancer? (Stop) 

A systematic review or meta-analysis that focuses on family history? (Stop) 

A systematic review or meta-analysis on another topic? (Stop) 

5. Is this a primary study? 

No (Stop) 

Yes/Can't Tell (Continue) 

6. Is there a reason to believe the citation FOCUSES on one or more of the following 3 

topics: Risk assessment model /risk stratification/risk algorithm OR awareness of cancer family 

history and uptake of preventative measures and/or health behavior OR harms or risks 

for individuals as a result of having their cancer family history taken. 

Yes (Include) 

No (Exclude) 

B-1
Level 2 – Title and Abstract Screening 

Family History II, Screening level 2 

1. Is this a cancer clinical practice guideline/recommendation? 

Not a clinical practice guideline/recommendation (continue) 

A clinical practice guideline focus on diagnostic screening techniques (stop) 

A clinical practice guideline focus on therapeutic agents (stop) 

A clinical practice guideline focus on surgical procedure (stop) 

clinical practice guideline focus on genetic testing (stop) 

It is a clinical practice guideline/recommendation on another topic. (stop) 

2. Is this article a Systematic Review? 

Not a systematic review (Continue) 

A systematic review on behaviors and/or clinical preventive services to change/prevent 

persons risk for cancer? (Stop) 

It is a non-systematic review.(Stop) 

A systematic review on another topic? (Stop) 

3. 

Is this a citation focused on one of the following topics:

Risk assessment model /risk stratification/risk algorithm 

Is this about uptaking preventative measures and/or behavior change and/or clinical 

preventive services? 

Is this about harm/risk of collection of family history or provision of family history based 

risk information? 

Is this about harms/risk of genetic testing and/or genetic counseling? 

No (exclude) 

B-2
Level 3 – Full Text Screening - Phase I 

Family History II, Screening level 3 

1. Does this citation include the following cancers? (Check all that apply) 

Breast 

Ovarian 

Prostate 

Colorectal/colon/Rectal 

Cancer in general 

None of the above (exclude) 

2. Does this citation describe guidelines/recommendations on diagnoses including risk 

assessment or risk stratification? 

Yes (stop) 

No (continue)) 

Other guideline (stop) 

3. Is this a Systematic Review? 

Yes (continue) 

No (GO to Q6) 

4. Is this a systematic review on behaviors and /or clinical preventive services to 

change/reduce a person's risk for cancer? 

Yes (continue) 

No(stop) 

5. Is this article a Systematic Review on food, nutrition, physical activity, obesity, smoking, 

alcohol, and the prevention on cancer* published before 2006? (*see the list) 

Yes (stop) 

No (stop) 

6. What type of primary study is this citation? 

Cohort 

Case Control 

Experimental 

Others 

B-3
It is not a primary study (stop) 

B-4
7. Does this article describe risk prediction equations/mathematical models OR risk 

stratification algorithms OR Risk assessment model? 

Yes (continue) 

No (Go to Q9) 

8. Is the model based substantially on family history information? 

Yes (stop) 

No(stop) 

9. Is this article about the uptake of behaviours or clinical preventive services to reduce 

risk of cancer? 

Yes (continue) 

No (go to Q11) 

10. Does this article mention subjects have been informed of personal risk of breast, 

colorectal, prostate and/or ovarian cancer based on family history or at least had their 

family history taken? 

Yes (stop) 

No (stop) 

11. Is this article about harm/injury/increased risk for individuals as a result of having 

their cancer family history taken or the provision of family history based risk information?

Yes 

No 

12. Is this a dissertation, conference abstract, workshop proceeding, or an old guideline? 

Yes (exclude) 

B-5
Level 4 – Full Text Screening – Phase II 

Family History II, Screening level 4 (Q1234G) 

1. what question does this citation answer? 

Q1 (Go to Q2---5, Blue color) 

Q2 (Go to Q6---8, -Green color) 

Q3 (Go to Q9 ---13, -Red color) 

Q4 (Go to Q14---16, Purple color) 

Guideline (Go to Q17---20, Brown color)

none of the above 

2. Is the risk/algorithm designed to predict or categorize/stratify risk of cancer or risk of a 

cancer mutation? (Note that a model/ algorithm that focuses on treatment alone, should not be 

included. If the model/ algorithm also provides information on follow-up after the intervention 

(for example, surgery, or other treatments) that includes actions or recommendations based on 

family history) 

Yes 

No (stop) 

3. Is the risk/ algorithm system designed to stratify people into >= 2 risk categories 

OR provide a numerical point estimate or risk? 

Yes 

No 

(exclude) 

Not sure 

4. Does this study undertake validation on a sample that is unselected (for risk of cancer) 

and representative of a primary care sample? 

Yes 

No (specify reason) 

Not sure (specify reason) 

5. Reviewer comments: 

6. 

For SR what type of study designs are included in its eligibility criteria?

Randomized Controlled Trials (RCT)

B-6
Non-randomized controlled trials 

Uncontrolled trials (before-after) 

SR but None of the above 

Can not tell 

not a SR 

7. Is the intervention in this review one that is relevant for research question 2 (see list)? 

Yes 

No (stop) 

Not sure 

8. 

Does this paper have the appropriate Outcomes AND unselected POPULATION:

Yes 

Not sure 

No (specify reason) 

9. Does the POPULATION of this study include? 

General unselected population 

Primary care patients who are unselected 

Persons who are participating in a general screening program 

People with high risk of cancer, as estimated by an existing risk assessment system or a 

genetics specialist OR Populations sampled from specialist genetics clinics or cancer family 

clinics OR People who have had a genetic test for a mutation related to one of the cancers of 

interest OR Persons who have cancer (exclude if any of the above criteria are met) 

10. What is the STUDY DESIGN for this citation?

Randomized Clinical Trial 

Non-randomized Clinical Trial 

Before After-study 

Other (exclude) 

B-7
11. Does the study include the systematic provision of personal risk of breast, colorectal, 

prostate and/or ovarian cancer based on FAMILY HISTORY? (WITH OR WITHOUT 

Individual advice on appropriate risk reduction behaviors and/or services (where recommended 

behavior or service was considered standard of care at the time of the study)

Yes (continue) 

No (exclude) 

Can't tell 

12. Does this citation also address research Q4? 

Yes 

No 

Not sure 

13. Reviewer comments: 

14. What is the study design of this citation? 

Randomized Clinical Trial 

Non-randomized Clinical Trial 

Before After-study 

Other ( continue to next question))

15. Does the POPULATION of this study include? 

General unselected population. 

Primary care patients who are unselected 

Persons who are participating in a general screening program 

People with high risk of cancer, as estimated by an existing risk assessment system or a 

genetics specialist OR Populations sampled from specialist genetics clinics or cancer family 

clinics OR People who have had a genetic test for a mutation related to one of the cancers of 

interest OR Persons who have cancer (exclude if any of the above criteria are met) 

16. Does this paper have the appropriate Outcomes?

Yes 

Not sure (specify) 

No (specify reason) 

B-8
17. Is one of the aims of the guideline designed to predict or categorize/stratify risk of 

cancer or risk of a cancer mutation AND does the guideline include a family 

history component? 

(Note that some guidelines have multiple components (treatment, screening, management) 

and there must be an explicit indication of collecting cancer family history). 

Yes 

No 

(stop) 

Not sure 

18. Is the guideline system designed to stratify people into greater than or equal to 2 risk 

categories OR provide a numerical point estimate or risk?

Yes 

No 

(exclude) 

Not sure 

19. Does this guideline delineate information about the accuracy or validity of the 

guideline? The accuracy can be expressed as diagnostic accuracy (sensitivity, specificity, 

positive predictive values, etc) for either predicting cancer or cancer mutation.

Yes 

No (specify reason) 

Not sure (specify reason) 

20. Reviewer comments: 

B-9
Family History II, Screening level 1- Guidelines 

1. Is this article non-English or a commentary, editorial or NON-systematic review? 

Yes (Stop) 

No (Continue) 

Instruction:

If the citation is in a language other than English, is a commentary or editorial or is a nonsystematic review (i.e. a review that is not systematic) you should answer "YES" and then go 

on to the next citation (don't forget to click "submit" or your answers won't be recorded). 

If the citation is for a PRIMAY study, a clinical practice guideline or a systematic review (or 

any study type not listed above) you should answer "NO" and then continue screening 

2. Does the citation include any one of the following cancers? 

Breast/Colorectal/Colon/ Rectal/Ovarian/Prostate/Cancer in general (Continue) 

None of the above (Stop) 

Instruction: 

Question 2: We are only interested in studies about Breast, Ovarian, Prostate and Colorectal 

Cancers. If the study does not specify the type of cancer, choose “cancer in general” 

3. Is this a cancer clinical practice guideline? 

Yes (Stop) 

No (Continue) 

4. Is this article a Systematic Review? 

Not a systematic review (Continue) 

A systematic review on an intervention to PREVENT, reduce the risk of cancer? (Stop)

A systematic review about family history? (Stop) 

A systematic review on another topic? (Stop) 

Instruction 1 for Question 4: 

Please note that the word INTERVENTION is used in the generic sense to indicate a lifestyle 

or service obtained that will result in a CHANGE in a person's risk for cancer. This change 

can be positive or negative (e.g. alcohol consumption is associated with an increased risk of 

some cancers). The review does NOT have to show that the lifestyle change or preventive 

service CAUSES change in cancer risk, only that it is ASSOCIATED with a change in risk. 

B-10
That means that for both citation A and B below you should choose would choose “A 

systematic review or meta-analysis that focuses on an intervention to prevent or reduce the risk 

of cancer?” 

A. Low fat eating pattern intervention and risk of colorectal cancer in postmenopausal 

women: a systematic review 

B. Alcohol consumption is associated with an increased risk of distal colon and rectal 

cancer in Japanese men: a meta-analysis 

Instruction 2 for Question 4: 

Look carefully for words like “systematic review”, “meta analysis”, “Cochrane 

review” or “pooling”, or some description of the methods used to assemble papers: 

- sort of detailed search info such as describes methods for searching 1 or more 

databases (MEDLINE, etc) 

- discusses inclusion and exclusion criteria 

NB: 

• This can include people who have had cancer and are taking steps to avoid a 

RECURRENCE 

• Exclude if the intervention is CLEARLY USED ONLY to TREAT/ MANAGE 

cancer patients rather than PREVENT recurrences. 

• For example, if radiation therapy or drugs are being used in patients with cancer, it 

is likely that this study is focused on TREATING patients with cancer, not 

preventing cancer or RECURRENCES. 

Examples of common interventions to PREVENT or reduce the risk of cancer (list is 

partial, include any intervention that you find) 

Breast:

Specific behaviors: 

• breast self-examination 

Specific clinical preventive services: 

• annual clinical examination 

• mammography 

• clinical breast examination 

• cancer chemoprevention 

• magnetic resonance imaging breast screening (MRI) 

• genetic counseling +/- genetic testing 

• risk-reduction mastectomy/oophorectomy (RRM/O) 

Colorectal:

Specific clinical preventive services: 

• Screening/surveillance activities 

B-11
- FOB test 

- sigmoidoscopy 

- digital rectal exam 

- colonoscopy 

• genetic counseling +/- genetic testing 

Ovarian:

Specific clinical preventive services: 

• genetic counseling +/- genetic testing 

• prophylactic oophorectomy 

• ovarian screening 

• genetic counseling +/- genetic testing 

Prostate:

Specific clinical preventive services: 

• Screening/surveillance activities: 

- PSA test 

- digital rectal examination 

• chemoprevention 

• genetic counseling +/- genetic testing 

General behaviors for all four cancers: 

• regular exercise/physical activity 

• high fiber diet 

• increased fruit and vegetable consumption 

• low fat diet 

• smoking cessation 

• reduction in alcohol intake 

• seeking health care advice

5. Is this a Primary Study? 

No (Stop) 

Yes (Continue) 

Can’t Tell (Continue) 

•

6. Is there a reason to believe the citation FOCUSES on one or more of the following 3 

topics: Risk assessment model /risk stratification/risk algorithm OR awareness of cancer family 

history and uptake of preventative measures and/or health behavior OR harms or risks 

for individuals as a result of having their cancer family history taken. 

Yes (Include) 

B-12
No (Exclude) 

Instruction: question 6. 

We are including primary studies that focus on one or more of the 3 following topics:

1. Some risk assessment model /risk stratification/risk algorithm tools are listed below. Note 

this is only a partial list; include any you find that you think are risk assessment tools. 

• Gail 

• Claus 

• Tyrer-Cuzick 

• Couch 

• BRCA-PRO 

• UK Cancer Family Study Group 

• BOADICEA 

• French National agency for health evaluation 

• National Breast Cancer Centre (Australia) 

• Amsterdam and modified Amsterdam 

• Scottish Cancer Group 

• MYRIAD (Frank) 

• Bethesda 

• Manchester 

• USPSTF 

• FHAT 

• Jonker 

• Ontario Stratification algorithm

Definition of Risk Assessment tools (models or algorithm) 

Models that stratify risk use several different pieces of information. Based on this information 

patients are categorized into high, medium or low risk for either getting cancer or having a 

high risk gene (mutation).A tool/ model/ algorithm usually has a name (see provided list) and 

is almost always used by physicians 

2. Awareness of cancer family history and uptake of preventative measures and/or 

health behaviors 

• Include if the abstract states that based on the participants knowing their cancer family 

history, are evaluated for their uptake of specific actions. These generally include 

either behavioral changes (e.g. changes in diet or activity level, self-exam) or clinical 

preventive services (e.g., chemoprevention, prophylactic surgery, screening,). 

• Exclude if it is CLEARLY an intervention ONLY to improve the outcome for those 

WITH cancer. For example, a mastectomy that is not prophylactic (preventing the 

cancer from occurring) but is being undertaken to TREAT the cancer. This should be 

excluded as it is not showing that the preventative measure (i.e. mastectomy) was not 

undertaken to prevent cancer. Be careful as interventions like Tamoxifen as a treatment 

versus its use as a prevention measure. We are interested in it with regards to 

prevention. 

B-13
B-14

• If there is any doubt includes the abstract OR send us a message with your queries. 

3. Harms or risks for individuals as a result of having their cancer family history taken. 

Examples of HARMS include: 

• Psychological impacts like fear, depression, anxiety, family function impacts, 

discrimination in employment or insurance, fatalism, health problems, quality of life 

issues, deciding not to have children because of FH 

• Behaviour changes due to perception or misperception of risk (i.e. fatalism or thinking 

you are low risk) examples: someone starts eating a high fat diet or quits exercising 

because they think they are going to get cancer anyway or because they believe that 

they aren’t at risk. 

Exclude articles that 

• Focus on the negative impacts of HAVING cancer (there will be quite a few of these). 

So if spouse leaves because their partner HAS cancer, exclude. 

• BUT if they leave because they learned that their partner has a family history of cancer 

(increased risk real or perceived), include it. If the distinction is unclear err on the side 

of caution and include it. 

• Exclude articles if the harm is clearly secondary for example, if a person has a 

prophylactic mastectomy because of their family history and has surgical 

complications. If the distinction is unclear err on the side of caution and include it. 

• Any harms that result from having undertaken a preventive measure, like a 

prophylactic mastectomy followed by surgical complications, should be excluded. 
Appendix C – Eligible Studies Extracted and Those 

Retained But Not Extracted 

Table 1. Eligible Studies Extracted and Those Retained But Not Extracted 

Retained But Not Extracted Superseded by (extracted) 

Huang 20061

 

Huang 20062 Bardia 20083

 

Moayyedi 20064

 Hewitson 20075 

Walsh 20036

 Hewitson 20075 

Bonovas 20077

 

Bonovas 20058 Browning 20079

 

Hoffmeister 200610 Dubé 200711 

Asano 200412 Dubé 200711 

Coulter 200613 Alkhenizan 200714 

Dale 200615 Browning 20079

 

Heresbach 200616 Hewitson 20075

 

Hackshaw 200317 Kosters 200318

Gotzsche 200619

Kerr 200720

Bristol SLR Team 2006 21

Ilic 200622

Eligible, but did not report usable data 

Dutch Review Team, Bakker 200623 

Italian Review Team, Agnoli 200524 

Eligible, but no eligible intervention studies identified 

Mahmud 200425 

Rostom 200726 

Weingarten 200827 

Brett 200528 

Watson 200529 

C-1
C-2

Reference List for Appendix C – Studies Retained But Not 

Extracted

 1. Huang HY, Caballero B, Chang S et al. 

Multivitamin/mineral supplements and prevention 

of chronic disease. Evid Rep Technol Assess 

No.139, AHRQ Publication No.06-E012. (Prepared 

by The Johns Hopkins University Evidence-based 

Practice Center under Contract No.290-02-0018). 

Rockville, MD: Agency for Healthcare Research 

and Quality; 2006 May. PM:17764205

 2. Huang HY, Caballero B, Chang S, et al. The 

efficacy and safety of multivitamin and mineral 

supplement use to prevent cancer and chronic 

disease in adults: a systematic review for a National 

Institutes of Health state-of-the-science conference. 

[Review] [44 refs]. Ann Intern Med 

2006;145(5):372-85. 

 3. Bardia A, Tleyjeh IM, Cerhan JR, et al. Efficacy of 

antioxidant supplementation in reducing primary 

cancer incidence and mortality: systematic review 

and meta-analysis. [Review] [73 refs]. Mayo Clin 

Proc 2008;83(1):23-34. 

 4. Moayyedi P, Achkar E. Does fecal occult blood 

testing really reduce mortality? A reanalysis of 

systematic review data.[Review] [25 refs]. Am J 

Gastroenterol 2006;101(2):380-4. 

 5. Hewitson P, Glasziou P, Irwig L, et al. Screening 

for colorectal cancer using the faecal occult blood 

test, Hemoccult.[update of Cochrane Database Syst 

Rev. 2000;(2):CD001216; PMID: 10796760]. 

[Review] [46 refs]. Cochrane Database Syst Rev 

2007;(1):CD001216 

 6. Walsh JM, Terdiman JP. Colorectal cancer 

screening: scientific review.[Review] [105 refs]. 

JAMA 2003;289(10):1288-96. 

 7. Bonovas S, Filioussi K, Flordellis CS, et al. Statins 

and the risk of colorectal cancer: a meta-analysis of 

18 studies involving more than 1.5 million patients. 

J Clin Oncol 2007;25(23):3462-8. 

 8. Bonovas S, Filioussi K, Tsavaris N, et al. Use of 

statins and breast cancer: A meta-analysis of seven 

randomized clinical trials and nine observational 

studies. J Clin Oncol 2005;23(34):8606-12. 

 9. Browning DR, Martin RM. Statins and risk of 

cancer: A systematic review and metaanalysis. Int J 

Cancer 2007;120(4):833-43. 

 10. Hoffmeister M, Chang-Claude J, Brenner H. Do 

older adults using NSAIDs have a reduced risk of 

colorectal cancer? Drugs Aging 2006;23(6):513-23. 

 11. Dube C, Rostom A, Lewin G, et al. The use of 

aspirin for primary prevention of colorectal cancer: 

a systematic review prepared for the U.S. 

Preventive Services Task Force. Ann Intern Med 

2007;146(5):365-75. 

 12. Asano TK, McLeod RS. Nonsteroidal antiinflammatory drugs and aspirin for the prevention 

of colorectal adenomas and cancer: a systematic 

review. [Review] [45 refs]. Dis Colon Rectum 

2004;47(5):665-73. 

 13. Coulter ID, Hardy ML, Morton SC, et al. 

Antioxidants Vitamin C and Vitamin E for the 

Prevention and Treatment of Cancer. J Gen Intern 

Med 2006;21(7):735-44. 

 14. Alkhenizan A, Hafez K. The role of vitamin E in 

the prevention of cancer: a meta-analysis of 

randomized controlled trials. Ann Saudi Med 

2007;27(6):409-14. 

 15. Dale KM, Coleman CI, Henyan NN, et al. Statins 

and cancer risk: a meta-analysis. JAMA 

2006;295(1):74-80. 

 16. Heresbach D, Manfredi S, D'halluin PN, et al. 

Review in depth and meta-analysis of controlled 

trials on colorectal cancer screening by faecal occult 

blood test. [Review] [61 refs]. Eur J Gastroenterol 

Hepatol 2006;18(4):427-33. 

 17. Hackshaw AK, Paul EA. Breast self-examination 

and death from breast cancer: a meta-analysis. Br J 

Cancer 2003;88(7):1047-53. 

 18. Kosters JP, Gotzsche PC. Regular self-examination 

or clinical examination for early detection of breast 

cancer [Review] [24 refs]. Cochrane Database Syst 

Rev 2003;(2):CD003373 

 19. Gotzsche PC, Nielsen M. Screening for breast 

cancer with mammography. Cochrane Database 

Syst Rev 2006;(4):CD001877 

 20. Kerr J, Day P, Broadstock M, et al. Systematic 

review of the effectiveness of population screening 

for colorectal cancer. [Review] [28 refs]. N Z Medl 

Jl 2007;120(1258):U2629 

 21. Bristol SLR Team 2006. Systematic Literature 

Review Report. The associations between food, 

nutrition, physical activity and the risk of prostate 

cancer and underlying mechanisms. World Cancer 

Research Fund/American Institute for Cancer 

Research, Food, Nutrition, Physical Activity, and 

the Prevention of Cancer: a Global Perspective. 

Washington, DC: 2006 Jun 30. 

 22. Ilic D, O'Connor D, Green S, et al. Screening for 

prostate cancer. Cochrane Database Syst Rev 2006; 

Issue 3, Art.No.: 

CD004720.DOI:10.1002/14651858.CD004720.pub

2: 

 23. Dutch Review Team 2006. Systematic Literature 

Review Report. The associations between food, 

nutrition and physical activity and the risk of 

colorectal cancer and underlying mechanisms. 

World Cancer Research Fund/American Institute 

for Cancer Research, Food, Nutrition, Physical 

Activity, and the Prevention of Cancer: a Global 

Perspective. Washington, DC: 2007. 

 24. Italian Review Team 2005. Systematic Literature 

Review Report. The Associations between Food, 

Nutrition and Physical Activity and the Risk of 

Breast Cancer and Underlying Mechanisms. World 

Cancer Research Fund/American Institute for 

Cancer Research, Food, Nutrition, Physical 
Activity, and the Prevention of Cancer: a Global 

Perspective. Washington, DC: 2007. 

 25. Mahmud S, Franco E, Aprikian A. Prostate cancer 

and use of nonsteroidal anti-inflammatory drugs: 

systematic review and meta-analysis. [Review] [43 

refs]. Br J Cancer 2004;90(1):93-9. 

 26. Rostom A, Dube C, Lewin G, et al. Nonsteroidal 

anti-inflammatory drugs and cyclooxygenase-2 

inhibitors for primary prevention of colorectal 

cancer: a systematic review prepared for the U.S. 

Preventive Services Task Force. Ann Intern Med 

2007;146(5):376-89. 

 27. Weingarten MA, Zalmanovici A, Yaphe J. Dietary 

calcium supplementation for preventing colorectal 

cancer and adenomatous polyps.[update of 

Cochrane Database Syst Rev. 2005;(3):CD003548; 

PMID: 16034903]. [Review] [38 refs]. Cochrane 

Database Syst Rev 2008;(1):CD003548 

 28. Brett J, Bankhead C, Henderson B, et al. The 

psychological impact of mammographic screening. 

A systematic review. [Review] [74 refs]. 

Psychooncology 2005;14(11):917-38. 

 29. Watson EK, Henderson BJ, Brett J, et al. The 

psychological impact of mammographic screening 

on women with a family history of breast cancer--a 

systematic review. [Review] [26 refs]. 

Psychooncology 2005;14(11):939-48. 

C-3
Appendix D - Excluded Studies 

1. Abbadessa G, Santoro A, Claudio PP. 42nd 

Annual Meeting of the American Society of 

Clinical Oncology (ASCO) (June 2-6, Atlanta) 

2006. Drugs of the Future 2006;31(7):617-23. 

Excluded: Not an eligible study design, OVIDEmbase. 

2. Abdel-Fattah M, Zaki A, Bassili A, et al. Breast 

self-examination practice and its impact on breast 

cancer diagnosis in Alexandria, Egypt. East 

Mediterr Health J 2000;6(1):34-40. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

3. Absetz P, Aro AR, Sutton SR. Experience with 

breast cancer, pre-screening perceived 

susceptibility and the psychological impact of 

screening. Psychooncology 2003;12(4):305-18. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

4. Abu-Rustum NR, Herbolsheimer H. Breast 

cancer risk assessment in indigent women at a 

public hospital. Gynecol Oncol 2001;81(2):287-

90. Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

5. ACOG: American College of Obstetricians and 

Gynecologists. ACOG practice bulletin. Clinical 

management guidelines for obstetriciangynecologists. Number 42, April 2003. Breast 

cancer screening. Obst Gynecol 

2003;101(4):821-31. Excluded: Model does not 

categorize risk or validate, OVID-Medline. 

6. ACOG: American College of Obstetricians and 

Gynecologists. ACOG practice bulletin. Breast 

cancer screening. Number 42, April 2003. Int J 

Gynaecol Obstet 2003;81(3):313-23. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

7. ACOG: American College of Obstetricians and 

Gynecologists. ACOG committee opinion. 

Routine cancer screening. Number 247, 

December 2000. Int J Gynaecol Obstet 

2003;82(2):241-5. Excluded: Model does not 

categorize risk or validate, OVID-Medline. 

8. ACOG: American College of Obstetricians and 

Gynecologists .ACOG Committee on 

Gynecologic Practice. Committee opinion no. 

356: Routine cancer screening. Obstet Gynecol 

2006;108(6):1611-3. Excluded: Model does not 

categorize risk or validate, OVID-Embase. 

9. Agrawal A, Fentiman IS. NSAIDs and breast 

cancer: A possible prevention and treatment 

strategy. Int J Clin Pract 2008;62(3):444-9. 

Excluded: Not an eligible study design, OVIDEmbase. 

10. Ahmed NU, Fort JG, Elzey JD, et al. 

Empowering factors in repeat mammography: 

insights from the stories of underserved women. J 

Ambulatory Care Manage 2004;27(4):348-55. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

11. Ahmed NU, Fort JG, Elzey JD, et al. 

Empowering factors for regular mammography 

screening in under-served populations: pilot 

survey results in Tennessee.[see comment]. Ethn 

Dis 2005;15(3):387-94. Excluded: Family 

history not systematically collected, OVIDMedline. 

12. Aiken LS, Fenaughty AM, West SG, et al. 

Perceived determinants of risk for breast cancer 

and the relations among objective risk, perceived 

risk, and screening behavior over time. Womens 

Health 1995;1(1):27-50. Excluded: Family 

history not systematically collected, OVIDMedline. 

13. Ainsworth PJ, Koscinski D, Fraser BP, et al. 

Family cancer histories predictive of a high risk 

of hereditary non-polyposis colorectal cancer 

associate significantly with a genomic 

rearrangement in hMSH2 or hMLH1. Clin Genet 

2004;66(3):183-8. Excluded: Family history not 

systematically collected, OVID-Medline. 

14. Aktan-Collan K, Mecklin JP, Jarvinen H, et al. 

Predictive genetic testing for hereditary nonpolyposis colorectal cancer: uptake and long-term 

satisfaction. Int J Cancer 2000;89(1):44-50. 

Excluded: Not an eligible population, OVIDMedline. 

15. Aktan-Collan K, Haukkala A, Pylvanainen K, et 

al. Direct contact in inviting high-risk members 

of hereditary colon cancer families to genetic 

counselling and DNA testing. J Med Genet 

2007;44(11):732-8. Excluded: Not an eligible 

population, OVID-Medline. 

16. Alamian A, Rouleau I, Simard J, et al. Use of 

dietary supplements among women at high risk 

of hereditary breast and ovarian cancer (HBOC) 

tested for cancer susceptibility. Nutr Cancer 

2006;54(2):157-65. Excluded: Not an eligible 

population, OVID-Medline. 

17. American Cancer Society. American Cancer 

Society issues redefined breast cancer screening 

guidelines. Iowa Med 93(5):27-Oct. Excluded: 

Model does not categorize risk or validate, 

OVID-Medline. 

18. American College of Obstetricians and 

Gynecologists. ACOG Committee Opinion No. 

384 November 2007: colonoscopy and colorectal 

cancer screening and prevention. Obstet Gynecol 

2007;110(5):1199-202. Excluded: Model does 

not categorize risk or validate, OVID-Medline. 

19. American Gastroenterological Association. 

American Gastroenterological Association 

medical position statement: hereditary colorectal 

cancer and genetic testing. Gastroenterology 

2001;121(1):195-7. Excluded: Model does not 

categorize risk or validate, OVID-Medline. 

D-1
20. American Society of Clinical Oncology. 

Statement of the American Society of Human 

Genetics on genetic testing for breast and ovarian 

cancer predisposition. Am J Hum Genet 

1994;55(5):i-iv Excluded: Model does not 

categorize risk or validate, OVID-Medline. 

21. American Society of Clinical Oncology. 

American Society of Clinical Oncology policy 

statement update: genetic testing for cancer 

susceptibility. J Clin Oncol 2003;21(12):2397-

406. Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

22. Amir E, Evans DG, Shenton A, et al. Evaluation 

of breast cancer risk assessment packages in the 

family history evaluation and screening 

programme. J Med Genet 2003;40(11):807-14. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

23. 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.[see comment]. Gynecol Oncol 

2002;85(1):3-8. Excluded: Family history not 

systematically collected, OVID-Medline. 

24. 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;189(4:Suppl):Suppl-7.Excluded: Family 

history not systematically collected, OVIDMedline. 

25. 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;12(4):314-20. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

26. Andersen MR, Nelson J, Peacock S, et al. Worry 

about ovarian cancer risk and use of screening by 

high-risk women: how you recruit affects what 

you find. Am J Med Genet 2004;Part(2):130-5. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

27. Anderson BO. Global Summit Consensus 

Conference on International Breast Health Care: 

Guidelines for countries with limited resources. 

Breast J 2003;9(SUPPL. 2):S40-S41 Excluded: 

Not an eligible study design, OVID-Embase. 

28. Andreeva VA, Unger JB, Pentz MA. Breast 

cancer among immigrants: A systematic review 

and new research directions. J Immigr Minor 

Health 2007;9(4):307-22. Excluded: Not an 

eligible population, OVID-Embase. 

29. Andrykowski MA, Zhang M, Pavlik EJ, et al. 

Factors associated with return for routine annual 

screening in an ovarian cancer screening 

program. Gynecol Oncol 2007;104(3):695-701. 

Excluded: Not an eligible study design, OVIDMedline. 

30. Anonymous. Colonoscopy in the screening and 

surveillance of individuals at increased risk for 

colorectal cancer. American Society for 

Gastrointestinal Endoscopy. Gastrointest Endosc 

1998;48(6):676-8. Excluded: Model does not 

categorize risk or validate, OVID-Medline. 

31. Anonymous. Bilateral prophylactic mastectomy 

in women with an increased risk of breast cancer. 

Tecnologica MAP 1999;Suppl:3-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

32. Anonymous. Assessing hereditary breast cancer 

risk. Cancer Pract 1999;7(6):279-84. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

33. Anonymous. Cancer predisposition genetic 

testing and risk assessment counseling. Oncology 

Nursing Society. Oncol Nurs Forum 

2000;27(9):1349 

Excluded: Not an eligible study design, OVIDMedline. 

34. Anonymous. Anxiety, depression in women at 

high risk for breast Cancer. Oncology News 

International 2002;11(5):50 

Excluded: Not an eligible study design, OVIDCinahl. 

35. Anonymous. Colorectal cancer screening: New 

recommendations. Consultant 2003;43(3):318-20. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

36. Anonymous. Simple programme predicts who is 

most at risk of breast cancer. S Afr Med J 

2004;Suid-Afrikaanse(5):337-8. 

Excluded: Not an eligible study design, OVIDMedline. 

37. Anonymous. The management of colorectal 

cancers. Eff Health Care 2004;8(3):1-11. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

38. Anonymous. Diseases: Management of patients 

presenting the first signs or a history of solid 

malignancy? Joint Bone Spine 2005;72(Suppl. 

1):S31-S38 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

39. Anonymous. Vitamins, minerals, supplements 

and dietary approaches. Focus on Alternative and 

Complementary Therapies 2005;10(3):227-32. 

Excluded: Not an eligible study design, OVIDEmbase. 

40. Anonymous. Updated guideline provides 

recommendations for surveillance after colorectal 

cancer. ASCO News & Forum 2006;1(1):20-1. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

41. Anonymous. American Cancer Society 

guidelines still advise yearly mammography for 

women aged 40 to 49 years. CA Cancer J Clinic 

2007;57(4):187-8. 

Excluded: Not an eligible study design, OVIDEmbase. 

D-2
42. Anonymous. Europe against colorectal cancer: 

Declaration of Brussels 9 May 2007. Z 

Gastroenterol 2008;46(SUPPL. 1):S2-S3 

Excluded: Not an eligible publication type, 

OVID-Embase. 

43. Antill Y, Reynolds J, Young MA, et al. Riskreducing surgery in women with familial 

susceptibility for breast and/or ovarian cancer. 

Eur J Cancer 2006;42(5):621-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

44. Antill YC, Reynolds J, Young MA, et al. 

Screening behavior in women at increased 

familial risk for breast cancer. Fam Cancer 

2006;5(4):359-68. 

Excluded: Not an eligible study design, OVIDMedline. 

45. Antoniou AC, Durocher F, Smith P, et al. 

BRCA1 and BRCA2 mutation predictions using 

the BOADICEA and BRCAPRO models and 

penetrance estimation in high-risk FrenchCanadian families. Breast Cancer Res 

2006;8(1):R3 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

46. Apicella C, Dowty JG, Dite GS, et al. Validation 

study of the LAMBDA model for predicting the 

BRCA1 or BRCA2 mutation carrier status of 

North American Ashkenazi Jewish women. Clin 

Genet 2007;72(2):87-97. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

47. Armstrong C. ACS recommendations on MRI 

and mammography for breast cancer screening. 

Am Fam Physician 2007;75(11):1712 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

48. Armstrong K, Moye E. What is the evidence on 

screening mammography for women in their 40s? 

J Fam Pract 2007;56(7):530 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

49. Armstrong K, Calzone K, Stopfer J, et al. Factors 

associated with decisions about clinical 

BRCA1/2 testing. Cancer Epidemiol Biomarkers 

Prev 2000;9(11):1251-4. 

Excluded: Not an eligible study design, OVIDMedline. 

50. Armstrong K, Weber B, FitzGerald G, et al. Life 

insurance and breast cancer risk assessment: 

adverse selection, genetic testing decisions, and 

discrimination. Am J Med Genet 

2003;Part(3):359-64. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

51. Armstrong K, Weber B, Stopfer J, et al. Early use 

of clinical BRCA1/2 testing: associations with 

race and breast cancer risk. Am J Med Genet 

2003;Part(2):154-60. 

Excluded: Not an eligible population, OVIDMedline. 

52. Armstrong K, Micco E, Carney A, et al. Racial 

differences in the use of BRCA1/2 testing among 

women with a family history of breast or ovarian 

cancer. JAMA 2005;293(14):1729-36. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

53. Armstrong K, Moye E, Williams S, et al. 

Screening mammography in women 40 to 49 

years of age: a systematic review for the 

American College of Physicians. Ann Intern Med 

2007;146(7):516-26. 

Excluded: Not an eligible population, OVIDMedline. 

54. Asano, TK, McLeod, et al. Vitamins and 

minerals for the prevention of colorectal 

adenomas and carcinomas [Protocol]. Cochrane 

Database Syst Rev 2008;(1): 

Excluded: Not an eligible study design, OVIDCochrane. 

55. Asano, TK, McLeod, et al. Dietary fibre for the 

prevention of colorectal adenomas and 

carcinomas [Systematic Review]. Cochrane 

Database Syst Rev 2008;(1): 

Excluded: Not an eligible intervention or 

outcome, OVID-Cochrane. 

56. ASCO clinical practice guidelines highlight new 

strategies for breast cancer surveillance, HER-2 

testing. ASCO News Forum 2007;2(1):32-3. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

57. Association of Breast Surgery @ BASO Royal 

College of Surgeons of England. Guidelines for 

the management of symptomatic breast disease. 

Eur J Surg Oncol 2005;31(SUPPL.):S1-S21 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

58. Astorg P. Dietary n - 6 and n - 3 polyunsaturated 

fatty acids and prostate cancer risk: A review of 

epidemiological and experimental evidence. 

Cancer Causes Control 2004;15(4):367-86. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

59. Audrain J, Schwartz MD, Lerman C, et al. 

Psychological distress in women seeking genetic 

counseling for breast-ovarian cancer risk: the 

contributions of personality and appraisal. Ann 

Behav Med 1997;19(4):370-7. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

60. Aus G, Abbou CC, Bolla M, et al. EAU 

guidelines on prostate cancer. Eur Urol 

2005;48(4):546-51. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

61. Azaiza F, Cohen M. Health beliefs and rate of 

breast cancer screening among Arab women. J 

Womens Health 2006;15(5):520-30. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

D-3
62. Aziz O, Athanasiou T, Fazio VW, et al. Metaanalysis of observational studies of ileorectal 

versus ileal pouch-anal anastomosis for familial 

adenomatous polyposis. Br J Surg 

2006;93(4):407-17. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

63. Azzarello,L.M. Psychological factors associated 

with skin cancer detection behaviors in 

individuals with a family history of melanoma 

Azzarello. 2006 

Excluded: Not an eligible intervention or 

outcome, OVID-PsycInfo. 

64. Badger TM, Ronis MJJ, Simmen RCM, et al. Soy 

protein isolate and protection against cancer. J 

Am Coll Nutr 2005;24(2):146S-9S. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

65. Baider L, Ever-Hadani P, Kaplan De-Nour A. 

Psychological distress in healthy women with 

familial breast cancer: like mother, like daughter? 

Int J Psychiatry Med 1999;29(4):411-20. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

66. Baker S, Wall M, Bloomfield A. Breast cancer 

screening for women aged 40 to 49 years--what 

does the evidence mean for New Zealand? N Z 

Med J 2005;118(1221):U1628 

Excluded: Not an eligible study design, OVIDMedline. 

67. Balmana J, Stoffel EM, Emmons KM, et al. 

Comparison of motivations and concerns for 

genetic testing in hereditary colorectal and breast 

cancer syndromes. J Med Genet 2004;41(4):e44 

Excluded: Not an eligible study design, OVIDMedline. 

68. Banerjee S, Van Dam J. CT colonography for 

colon cancer screening. Gastrointest Endosc 

2006;63(1):121-33. 

Excluded: Not an eligible population, OVIDCinahl. 

69. Bankhead CR, Brett J, Bukach C, et al. The 

impact of screening on future health-promoting 

behaviours and health beliefs: a systematic 

review. [Review] [264 refs]. Health Technol 

Assess 2003;7(42):1-92. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

70. Barcenas CH, Hosain GM, Arun B, et al. 

Assessing BRCA carrier probabilities in extended 

families. J Clin Oncol 2006;24(3):354-60. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

71. Barkun AN, Jobin G, Cousineau G, et al. The 

Quebec Association of Gastroenterology position 

paper on colorectal cancer screening - 

2003.[erratum appears in Can J Gastroenterol. 

2004 Sep;18(9):591]. Can J Gastroenterol 

2004;18(8):509-19. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

72. Barlow WE, White E, Ballard-Barbash R, et al. 

Prospective breast cancer risk prediction model 

for women undergoing screening mammography. 

J Natl Cancer Inst 2006;98(17):1204-14. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

73. Barnsley GP, Grunfeld E, Coyle D, et al. 

Surveillance mammography following the 

treatment of primary breast cancer with breast 

reconstruction: a systematic review. Plast 

Reconstr Surg 2007;120(5):1125-32. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

74. Basch E, Bent S, Foppa I, et al. Marigold 

(Calendula officinalis L.): An evidence-based 

systematic review by the natural standard 

research collaboration. J Herb Pharmacother 

2006;6(3-4):135-59. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

75. Bassil KL, Vakil C, Sanborn M, et al. Cancer 

health effects of pesticides: systematic review. 

Can Fam Physician 2007;53(10):1704-11. 

Excluded: Not an eligible population, OVIDMedline. 

76. Becker,S.T. Breast cancer screening patterns 

related to mammography adherence among 

Northern Plains Tribes American Indian women 

2006 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

77. Beebe-Dimmer JL, Wood J, Gruber SB, et al. 

Use of complementary and alternative medicine 

in men with family history of prostate cancer: A 

pilot study. Urology 2004;63(2):282-7. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

78. Beery TA, Williams JK. Risk reduction and 

health promotion behaviors following genetic 

testing for adult-onset disorders. Genet Test 

2007;11(2):111-23. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

79. Bellentani S, Baldoni P, Petrella S, et al. A 

simple score for the identification of patients at 

high risk of organic diseases of the colon in the 

family doctor consulting room. Fam Pract 

1990;7(4):307-12. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

80. Benedict S, Goon G, Hoomani J, et al. Breast 

cancer detection by daughters of women with 

breast cancer.[see comment]. Cancer Pract 

1997;5(4):213-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

81. Benichou J, Gail MH, Mulvihill JJ. Graphs to 

estimate an individualized risk of breast cancer. J 

Clin Oncol 1996;14(1):103-10. 

Excluded: Not an eligible study design, OVIDMedline. 

D-4
82. Benjamin,O. The role of dispositional optimism, 

cancer specific fatalism, and psychological 

distress in patients participation in the brca1 and 

brca2 genetic testing Benjamin. 1998 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

83. Berg AO, U.S.Preventive Services Task Force. 

Screening for prostate cancer: recommendations 

and rationale. Am J Nurs 111;103(3):107-10. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

84. Berg AO, U.S.Preventive Services Task Force. 

Screening for prostate cancer: recommendations 

and rationale. The American Journal for Nurse 

Practitioners 2003;7(1):24-6. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

85. Berg AO, U.S.Preventive Services Task Force. 

Chemoprevention of breast cancer: 

recommendations and rationale. Am J Nurs 

2003;103(5):107 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

86. Bergmann M, Wolf B, Karner-Hanusch J. 

Hereditary colorectal cancer - Guidelines for 

clinical routine. European Surgery - Acta 

Chirurgica Austriaca 2006;38(1):59-62. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

87. Bermejo-Perez MJ, Marquez-Calderon S, LlanosMendez A. Effectiveness of preventive 

interventions in BRCA1/2 gene mutation carriers: 

a systematic review. Int J Cancer 

2007;121(2):225-31. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

88. Bermejo-Perez MJ, Marquez-Calderon S, LlanosMendez A. Cancer surveillance based on imaging 

techniques in carriers of BRCA1/2 gene 

mutations: a systematic review. Br J Radiol 

2008;81(963):172-9. 

Excluded: Not an eligible study design, OVIDMedline. 

89. Bermejo JL, Eng C, Hemminki K. Cancer 

characteristics in Swedish families fulfilling 

criteria for hereditary nonpolyposis colorectal 

cancer. Gastroenterology 2005;129(6):1889-99. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

90. Berry DA, Parmigiani G, Sanchez J, et al. 

Probability of carrying a mutation of breastovarian cancer gene BRCA1 based on family 

history. J Natl Cancer Inst 1997;89(3):227-38. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

91. Berry DA, Iversen ES, Jr., Gudbjartsson DF, et 

al. BRCAPRO validation, sensitivity of genetic 

testing of BRCA1/BRCA2, and prevalence of 

other breast cancer susceptibility genes. J Clin 

Oncol 2002;20(11):2701-12. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

92. Bertaccini A, Fandella A, Prayer-Galetti T, et al. 

Systematic development of clinical practice 

guidelines for prostate biopsies: A 3-year Italian 

project. Anticancer Res 2007;27(1 B):659-66. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

93. Bevers TB, Anderson BO, Bonaccio E, et al. 

Breast cancer screening and diagnosis: Clinical 

practice guidelines in oncology[trademark]. J 

Natl Compr Cancer Netw 2006;4(5):480-508. 

Excluded: Not an eligible publication type, 

OVID-Embase. 

94. Bianchi F, Galizia E, Bracci R, et al. 

Effectiveness of the CRCAPRO program in 

identifying patients suspected for HNPCC. Clin 

Genet 2007;71(2):158-64. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

95. Biswas S, Berry DA. Determining joint carrier 

probabilities of cancer-causing genes using 

Markov chain Monte Carlo methods. Genet 

Epidemiol 2005;29(2):141-54. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

96. Bjelakovic G, Nikolova D, Simonetti RG, et al. 

Antioxidant supplements for prevention of 

gastrointestinal cancers: A systematic review and 

meta-analysis. Lancet 2004;364(9441):1219-28. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

97. Bjelakovic G. Antioxidants don't prevent GI 

cancers, increase overall mortality. South African 

Family Practice 2005;47(1):18 

Excluded: Not an eligible study design, OVIDEmbase. 

98. Bjelakovic G, Nikolova D, Simonetti RG, et al. 

High-dose antioxidants to prevent cancer: Hype 

or hoax? Focus on Alternative and 

Complementary Therapies 2005;10(1):29-31. 

Excluded: Not an eligible study design, OVIDEmbase. 

99. Bjelakovic G, Nikoloval D. Antioxidants do not 

prevent colorectal cancer. J Fam Pract 

2006;55(10):849 

Excluded: Not an eligible study design, OVIDEmbase. 

100. Bjelakovic G, Nagorni A, Nikolova D, et al. 

Meta-analysis: antioxidant supplements for 

primary and secondary prevention of colorectal 

adenoma. Aliment Pharmacol Ther 

2006;24(2):281-91. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

101. Bjelakovic G, Nikolova D, Gluud LL, et al. 

Mortality in randomized trials of antioxidant 

supplements for primary and secondary 

prevention: Systematic review and meta-analysis. 

JAMA 2007;297(8):842-57. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

D-5
102. Blalock SJ, DeVellis BM, Afifi RA, et al. Risk 

perceptions and participation in colorectal cancer 

screening. Health Psychol 1990;9(6):792-806. 

Excluded: Not an eligible study design, OVIDPsycInfo. 

103. Bleiker EM, Menko FH, Taal BG, et al. 

Screening behavior of individuals at high risk for 

colorectal cancer. Gastroenterology 

2005;128(2):280-7. 

Excluded: Not an eligible study design, OVIDMedline. 

104. Blom J, Yin L, Liden A, et al. Toward 

understanding nonparticipation in sigmoidoscopy 

screening for colorectal cancer. Int J Cancer 

2008;122(7):1618-23. 

Excluded: Not an eligible study design, OVIDMedline. 

105. Bloom JR, Stewart SL, Chang S, et al. Effects of 

a telephone counseling intervention on sisters of 

young women with breast cancer. Prev Med 

2006;43(5):379-84. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

106. 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;15(11):2167-73. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

107. Bock CH, Peyser PA, Gruber SB, et al. Prostate 

cancer early detection practices among men with 

a family history of disease. Urology 

2003;62(3):470-5. 

Excluded: Not an eligible population, OVIDMedline. 

108. Bodd TL, Reichelt J, Heimdal K, et al. Uptake of 

BRCA1 genetic testing in adult sisters and 

daughters of known mutation carriers in Norway. 

J Genet Couns 2003;12(5):405-17. 

Excluded: Not an eligible population, OVIDMedline. 

109. Bodmer D, Ligtenberg MJ, Van Der Hout AH, et 

al. Optimal selection for BRCA1 and BRCA2 

mutation testing using a combination of 'easy to 

apply' probability models. Br J Cancer 

2006;95(6):757-62. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

110. Boggs BD, Stephens MM, Wallace R. How does 

colonoscopy compare with fecal occult blood 

testing as a screening tool for colon cancer? J 

Fam Pract 2005;54(11):996-7. 

Excluded: Not an eligible study design, OVIDEmbase. 

111. Bondy ML, Vogel VG, Halabi S, et al. 

Identification of women at increased risk for 

breast cancer in a population-based screening 

program. Cancer Epidemiol Biomarkers Prev 

1992;1(2):143-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

112. Bondy ML, Lustbader ED, Halabi S, et al. 

Validation of a breast cancer risk assessment 

model in women with a positive family history. J 

Natl Cancer Inst 1994;86(8):620-5. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

113. Bondy ML, Newman LA. Assessing breast 

cancer risk: evolution of the Gail Model. J Natl 

Cancer Inst 2006;98(17):1172-3. 

Excluded: Not an eligible study design, OVIDMedline. 

114. Bonovas S, Filioussi K, Sitaras NM. Do 

nonsteroidal anti-inflammatory drugs affect the 

risk of developing ovarian cancer? A metaanalysis. Br J Clin Pharmacol 2005;60(2):194-

203. 

Excluded: Not an eligible population, OVIDEmbase. 

115. Borry P, Stultiens L, Nys H, et al. Attitudes 

towards predictive genetic testing in minors for 

familial breast cancer: a systematic review. Crit 

Rev Oncol Hematol 2007;64(3):173-81. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

116. Bosserman LD, Smith JA, Hellerstedt B, et al. 

Hereditary cancer testing in community oncology 

practices. Community Oncology 2007;4(11 

SUPPL.):2-8. 

Excluded: Not an eligible study design, OVIDEmbase. 

117. Botkin JR, Smith KR, Croyle RT, et al. Genetic 

testing for a BRCA1 mutation: prophylactic 

surgery and screening behavior in women 2 years 

post testing. Am J Med Genet 2003;Part(3):201-

9. 

Excluded: Not an eligible population, OVIDMedline. 

118. Bouvier A-M, Faivre J, Lejeune C. Screening 

strategy of colorectal cancers in high risk cases. 

Acta Endoscopica 2002;32(4):623-31. 

Excluded: Not an eligible study design, OVIDEmbase. 

119. Bowen D, McTiernan A, Burke W, et al. 

Participation in breast cancer risk counseling 

among women with a family history. Cancer 

Epidemiol Biomarkers Prev 1999;8(7):581-5. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

120. Bowen DJ, Morasca AA, Meischke H. Measures 

and correlates of resilience. Women Health 

2003;38(2):65-76. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

121. Bowen DJ, Alfano CM, McGregor BA, et al. The 

relationship between perceived risk, affect, and 

health behaviors. Cancer Detect Prev 

2004;28(6):409-17. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

D-6
122. Bradbury AR, Ibe CN, Dignam JJ, et al. Uptake 

and timing of bilateral prophylactic salpingooophorectomy among BRCA1 and BRCA2 

mutation carriers. Genetics in Medicine 

2008;10(3):161-6. 

Excluded: Not an eligible population, OVIDEmbase. 

123. 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;61(2):181-7. 

Excluded: Not an eligible study design, OVIDMedline. 

124. Braithwaite D, Emery J, Walter F, et al. 

Psychological impact of genetic counseling for 

familial cancer: a systematic review and metaanalysis. J Natl Cancer Inst 2004;96(2):122-33. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

125. Braithwaite D, Sutton S, Mackay J, et al. 

Development of a risk assessment tool for 

women with a family history of breast cancer. 

Cancer Detect Prev 2005;29(5):433-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

126. Braithwaite RS, Chlebowski RT, Lau J, et al. 

Meta-analysis of vascular and neoplastic events 

associated with tamoxifen. J Gen Intern Med 

2003;18(11):937-47. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

127. Bratt O, Damber JE, Emanuelsson M, et al. Risk 

perception, screening practice and interest in 

genetic testing among unaffected men in families 

with hereditary prostate cancer. Eur J Cancer 

2000;36(2):235-41. 

Excluded: Not an eligible study design, OVIDMedline. 

128. Bratt O, Emanuelsson M, Gronberg H. 

Psychological aspects of screening in families 

with hereditary prostate cancer. Scand J Urol 

Nephrol 2003;37(1):5-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

129. Braun L. There's no doubt: Soy protects and 

promotes health. Australian Journal of Pharmacy 

2007;88(1044):52-3. 

Excluded: Not an eligible study design, OVIDEmbase. 

130. Brenneman AE. Colon cancer: an update on 

screening. JAAPA J Am Acad Physician Assist 

2008;21(3):17-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

131. Brewer NT, Salz T, Lillie SE. Systematic review: 

the long-term effects of false-positive 

mammograms. Ann Intern Med 2007;146(7):502-

10. Excluded: Not an eligible population, OVIDMedline. 

132. Broadstock M, Michie S, Marteau T. 

Psychological consequences of predictive genetic 

testing: a systematic review. Eur J Hum Genet 

2000;8(10):731-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

133. Brooks DD, Winawer SJ, Rex DK, et al. 

Colonoscopy surveillance after polypectomy and 

colorectal cancer resection. Am Fam Physician 

2008;77(7):995-1002. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

134. Brosnan CA. Review: colorectal cancer screening 

with the faecal occult blood test reduced 

colorectal cancer mortality. Evid Based Nurs 

2007;10(4):112 

Excluded: Not an eligible study design, OVIDCinahl. 

135. Brown SR, Baraza W, Hurlstone P. 

Chromoscopy versus conventional endoscopy for 

the detection of polyps in the colon and rectum. 

Cochrane Database of Syst Rev 

2007;(4):CD006439 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

136. Bruner DW, Baffoe-Bonnie A, Miller S, et al. 

Prostate cancer risk assessment program. A 

model for the early detection of prostate cancer. 

ONCOLOGY 1999;13(3):325-34. PM:10204154 

Excluded: not an eligible study design, 

137. Brunton M, Jordan C, Campbell I. Anxiety 

before, during, and after participation in a 

population-based screening mammography 

programme in Waikato Province, New Zealand. 

N Z Med J 2005;118(1209):U1299 

Excluded: Family history not systematically 

collected, OVID-Medline. 

138. Bryant RJ, Hamdy FC. Screening for prostate 

cancer: an update. Eur Urol 2008;53(1):37-44. 

Excluded: Not an eligible study design, OVIDMedline. 

139. Buchalter,A.J. Effects of coping on distress 

related to family history of breast cancer 

Buchalter. 2002 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

140. Bujanda L, Sarasqueta C, Zubiaurre L, et al. Low 

adherence to colonoscopy in the screening of 

first-degree relatives of patients with colorectal 

cancer. Gut 2007;56(12):1714-8. 

Excluded: Not an eligible study design, OVIDMedline. 

141. 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: Family history not systematically 

collected, OVID-Medline. 

D-7
142. Burch JA, Soares-Weiser K, St John DJ, et al. 

Diagnostic accuracy of faecal occult blood tests 

used in screening for colorectal cancer: a 

systematic review. J Med Screen 

2007;14(3):132-7. Excluded: Not an eligible 

population, OVID-Medline. 

143. Burt RW. Impact of family history on screening 

and surveillance. Gastrointest Endosc 

1999;49(3:Pt 2):t-4 .Excluded: Not an eligible 

study design, OVID-Medline. 

144. Bushnell CD, Goldstein LB. Risk of ischemic 

stroke with tamoxifen treatment for breast cancer: 

a meta-analysis. Neurology 2004;63(7):1230-3. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

145. Butow P, Meiser B, Price M, et al. Psychological 

morbidity in women at increased risk of 

developing breast cancer: a controlled study. 

Psychooncology 2005;14(3):196-203. 

Excluded: Not an eligible study design, OVIDMedline. 

146. Cairns S, Scholefield JH. Guidelines for 

colorectal cancer screening in high risk groups. 

Gut 2002;51:Suppl-2 

Excluded: Not an eligible study design, OVIDMedline. 

147. Calonge N. Screening for ovarian cancer: 

Recommendation statement. Am Fam Physician 

2005;71(4):759-62. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

148. Calonge N. U.S. preventive services task force - 

Genetic risk assessment and BRCA mutation 

testing for breast and ovarian cancer 

susceptibility: Recommendation statement. Am 

Fam Physician 2006;73(5):869-77. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

149. 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: Family history not systematically 

collected, OVID-Medline. 

150. Capalbo C, Ricevuto E, Vestri A, et al. 

Improving the accuracy of BRCA1/2 mutation 

prediction: validation of the novel countrycustomized IC software. Eur J Hum Genet 

2006;14(1):49-54. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

151. Capalbo C, Ricevuto E, Vestri A, et al. BRCA1 

and BRCA2 genetic testing in Italian breast 

and/or ovarian cancer families: mutation 

spectrum and prevalence and analysis of mutation 

prediction models. Ann Oncol 2006;17:Suppl-40 

Excluded: Family history not systematically 

collected, OVID-Medline. 

152. 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: Family history not systematically 

collected, OVID-Medline. 

153. Cappelli M, Hunter AGW, Stern H, et al. 

Participation rates of Ashkenazi Jews in a colon 

cancer community-based screening/prevention 

study. Clin Genet 2002;61(2):104-14. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

154. Carlson RW, Moench SJ, Hammond ME, et al. 

HER2 testing in breast cancer: NCCN Task Force 

report and recommendations. J Natl Compr 

Cancer Netw 2004;4:Suppl-22 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

155. Carlsson AH, Bjorvatn C, Engebretsen LF, et al. 

Psychosocial factors associated with quality of 

life among individuals attending genetic 

counseling for hereditary cancer. J Genet Couns 

2004;13(5):425-45. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

156. Carpentieri DF, Qualman SJ, Bowen J, et al. 

Protocol for the examination of specimens from 

pediatric and adult patients with osseous and 

extraosseous Ewing sarcoma family of tumors, 

including peripheral primitive neuroectodermal 

tumor and Ewing sarcoma. Arch Pathol Lab Med 

2005;129(7):866-73. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

157. Ceber E, Soyer MT, Ciceklioglu M, et al. Breast 

cancer risk assessment and risk perception on 

nurses and midwives in Bornova Health District 

in Turkey. Cancer Nurs 2006;29(3):244-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

158. Chalmers K, Thomson K. Coming to terms with 

the risk of breast cancer: perceptions of women 

with primary relatives with breast cancer. Qual 

Health Res 1996;6(2):256-82. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

159. Chalmers KI, Luker KA. Breast self-care 

practices in women with primary relatives with 

breast cancer. J Adv Nurs 1996;23(6):1212-20. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

160. Champion VL. Compliance with guidelines for 

mammography screening. Cancer Detect Prev 

1992;16(4):253-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

D-8
161. Chan SC. Practice of breast self-examination 

amongst women attending a Malaysian Well 

Person's Clinic. Med J Malaysia 1999;54(4):433-

7. Excluded: Not an eligible study design, OVIDMedline. 

162. Chao A, Connell CJ, Cokkinides V, et al. 

Underuse of screening sigmoidoscopy and 

colonoscopy in a large cohort of US adults. Am J 

Public Health 2004;94(10):1775-81. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

163. Chatterjee N, Wacholder S. A marginal 

likelihood approach for estimating penetrance 

from kin-cohort designs. Biometrics 

2001;57(1):245-52. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

164. Chen J, Pee D, Ayyagari R, et al. Projecting 

absolute invasive breast cancer risk in white 

women with a model that includes 

mammographic density. J Natl Cancer Inst 

2006;98(17):1215-26. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

165. Chen K, Qiu J-L, Zhang Y, et al. Meta analysis 

of risk factors for colorectal cancer. World J 

Gastroenterol 2003;9(7):1598-600. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

166. Chen S, Wang W, Lee S, et al. Prediction of 

germline mutations and cancer risk in the Lynch 

syndrome.[see comment]. JAMA 

2006;296(12):1479-87. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

167. Chen S, Parmigiani G. Meta-analysis of BRCA1 

and BRCA2 penetrance. J Clin Oncol 

2007;25(11):1329-33. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

168. Chiao EY, Giordano TP, Palefsky JM, et al. 

Screening HIV-infected individuals for anal 

cancer precursor lesions: a systematic review. 

Clin Infect Dis 2006;43(2):223-33. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

169. Chikhaoui Y, Gelinas H, Joseph L, et al. Costminimization analysis of genetic testing versus 

clinical screening of at-risk relatives for familial 

adenomatous polyposis. Int J Technol Assess 

Health Care 2002;18(1):67-80. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

170. Cho E, Smith-Warner SA, Ritz J, et al. Alcohol 

intake and colorectal cancer: a pooled analysis of 

8 cohort studies. Ann Intern Med 

2004;140(8):603-13. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

171. Christman LK, Abdulla R, Jacobsen PB, et al. 

Colorectal cancer screening among a sample of 

community health center attendees. J Health Care 

Poor & Underserved 2004;15(2):281-93. 

Excluded: Not an eligible study design, OVIDMedline. 

172. Church J, Lowry A, Simmang C, et al. Practice 

parameters for the identification and testing of 

patients at risk for dominantly inherited 

colorectal cancer--supporting documentation. 

Dis Colon Rectum 2001;44(10):1404-12. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

173. Ciliska D, Robinson P, Armour T, et al. Diffusion 

and dissemination of evidence-based dietary 

strategies for the prevention of cancer. Nutr J 

2005;4:13 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

174. Claes E, Evers-Kiebooms G, Decruyenaere M, et 

al. Surveillance behavior and prophylactic 

surgery after predictive testing for hereditary 

breast/ovarian cancer. Behav Med 

2005;31(3):93-105. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

175. Clark MA, Rakowski W, Bonacore LB. Repeat 

mammography: prevalence estimates and 

considerations for assessment. Ann Behav Med 

2003;26(3):201-11. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

176. Clarke M. Tamoxifen for early breast cancer. 

Cochrane Database Syst Rev 2001;(1):CD000486 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

177. Clarke M. Tamoxifen for early breast cancer 

[Systematic Review]. Cochrane Database of Syst 

Rev 2008;(1) 2008;(1): 

Excluded: Not an eligible intervention or 

outcome, OVID-Cochrane. 

178. Claus EB, Risch N, Thompson WD. The 

calculation of breast cancer risk for women with 

a first degree family history of ovarian cancer. 

Breast Cancer Res Treat 1993;28(2):115-20. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

179. Claus EB, Risch N, Thompson WD. Autosomal 

dominant inheritance of early-onset breast cancer. 

Implications for risk prediction. Cancer 

1994;73(3):643-51. PM:8299086

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

180. Clavel-Chapelon F, Joseph R, Goulard H. 

Surveillance behavior of women with a reported 

family history of colorectal cancer. Prev Med 

1999;28(2):174-8. 

Excluded: Not an eligible study design, OVIDMedline. 

D-9
181. Codori AM, Petersen GM, Miglioretti DL, et al. 

Health beliefs and endoscopic screening for 

colorectal cancer: potential for cancer prevention. 

Prev Med 2001;33(2:Pt 1):t-36 

Excluded: Family history not systematically 

collected, OVID-Medline. 

182. Cohen M. First-degree relatives of breast-cancer 

patients: cognitive perceptions, coping, and 

adherence to breast self-examination. Behav Med 

2002;28(1):15-22. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

183. Cohen M. Breast cancer 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: Family history not systematically 

collected, OVID-Embase. 

184. Collins KS, Collins SK. Professional issues. 

Cancer screening recommendations. Radiat 

Therapist 2004;13(2):137-9. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

185. Collins V, Meiser B, Gaff C, et al. Screening and 

preventive behaviors one year after predictive 

genetic testing for hereditary nonpolyposis 

colorectal carcinoma. Cancer 2005;104(2):273-

81. 

Excluded: Not an eligible population, OVIDMedline. 

186. Colomer R, Vinas G, Beltran M, et al. Validation 

of the 2001 St Gallen risk categories for nodenegative breast cancer using a database from the 

Spanish Breast Cancer Research Group 

(GEICAM). J Clin Oncol 2004;22(5):961-2. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

187. Cormier L, Valeri A, Azzouzi R, et al. Worry and 

attitude of men in at-risk families for prostate 

cancer about genetic susceptibility and genetic 

testing. Prostate 2002;51(4):276-85. 

Excluded: Not an eligible study design, OVIDMedline. 

188. Cormier L, Reid K, Kwan L, et al. Screening 

behavior in brothers and sons of men with 

prostate cancer. J Urol 2003;169(5):1715-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

189. Corpet DE, Pierre F. How good are rodent 

models of carcinogenesis in predicting efficacy in 

humans? A systematic review and meta-analysis 

of colon chemoprevention in rats, mice and men. 

Eur J Cancer 2005;41(13):1911-22. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

190. Costantino JP, Gail MH, Pee D, et al. Validation 

studies for models projecting the risk of invasive 

and total breast cancer incidence. J Natl Cancer 

Inst 1999;91(18):1541-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

191. Costanza ME, Stoddard A, Gaw VP, et al. The 

risk factors of age and family history and their 

relationship to screening mammography 

utilization. J Am Geriatr Soc 1992;40(8):774-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

192. 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: Family history not systematically 

collected, OVID-Medline. 

193. Cottet V, Pariente A, Nalet B, et al. Low 

compliance with colonoscopic screening in firstdegree relatives of patients with large adenomas. 

Aliment Pharmacol Ther 2006;24(1):101-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

194. Coughlin L. American Cancer Society releases 

annual guidelines for the early detection of 

cancer. Am Fam Physician 2005;71(11):2202-5. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

195. Coulson AS, Glasspool DW, Fox J, et al. RAGs: 

A novel approach to computerized genetic risk 

assessment and decision support from pedigrees. 

Methods Inf Med 2001;40(4):315-22. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

196. Coyne JC, Kruus L, Racioppo M, et al. What do 

ratings of cancer-specific distress mean among 

women at high risk of breast and ovarian cancer? 

Am J Med Genet 2003;Part(3):222-8. 

Excluded: Not an eligible study design, OVIDMedline. 

197. Cravo ML, Fidalgo PO, Lage PA, et al. 

Validation and simplification of Bethesda 

guidelines for identifying apparently sporadic 

forms of colorectal carcinoma with microsatellite 

instability. Cancer 1999;85(4):779-85. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

198. Cui Y, Peterson NB, Hargreaves M, et al. 

Mammography use in the Southern Cohort Study 

(United States). J Health Care Poor Underserved 

2007;18(4):Supplement-17 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

199. 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;84(5):594-9. 

Excluded: Not an eligible study design, OVIDMedline. 

200. Cullen J, Schwartz MD, Lawrence WF, et al. 

Short-term impact of cancer prevention and 

screening activities on quality of life. J Clin 

Oncol 2004;22(5):943-52. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

D-10
201. Culver J, Burke W, Yasui Y, et al. Participation 

in breast cancer genetic counseling: the influence 

of educational level, ethnic background, and risk 

perception. J Genetic Couns 2001;10(3):215-31. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

202. Dai Z, Xu YC, Niu L. Obesity and colorectal 

cancer risk: a meta-analysis of cohort studies. 

World J Gastroenterol 2007;13(31):4199-206. 

Excluded: Not an eligible population, OVIDMedline. 

203. Daly MB, Lerman CL, Ross E, et al. Gail model 

breast cancer risk components are poor predictors 

of risk perception and screening behavior. Breast 

Cancer Res Treat 1996;41(1):59-70. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

204. Davila RE, Rajan E, Baron TH, et al. ASGE 

guideline: colorectal cancer screening and 

surveillance.[erratum appears in Gastrointest 

Endosc. 2006 May;63(6):892 Note: Adler, 

Douglas G [added]; Egan, James V [added]; 

Faigel, Douglas O [added]; Gan, Seng-Ian 

[added]; Hirota, William K [added]; Leighton, 

Jonathan A [added]; Lichtenstein, David [added]; 

Qureshi, Waqar A [added]; Shen, Bo [added]; 

Zuckerman, Marc J [added]; VanGuilder, Trina 

[added]; Fanelli, Robert D [added]]. Gastrointest 

Endosc 2006;63(4):546-57. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

205. Dawson SJ, Price MA, Jenkins MA, et al. Cancer 

risk management practices of noncarriers within 

BRCA1/2 mutation positive families in the 

Kathleen Cuningham Foundation Consortium for 

Research into Familial Breast Cancer. J Clin 

Oncol 2008;26(2):225-32. 

Excluded: Not an eligible population, OVIDMedline. 

206. De Bock GH, van Asperen CJ, de Vries JM, et al. 

How women with a family history of breast 

cancer and their general practitioners act on 

genetic advice in general practice: prospective 

longitudinal study. BMJ 2001;322(7277):26-7. 

Excluded: Not an eligible study design, OVIDMedline. 

207. De Bock GH, Bonnema J, Van Der Hage J., et al. 

Effectiveness of routine visits and routine tests in 

detecting isolated locoregional recurrences after 

treatment for early-stage invasive breast cancer: 

A meta-analysis and systematic review. J Clin 

Oncol 2004;22(19):4010-8. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

208. de la Hoya M, Diez O, Perez-Segura P, et al. Pretest prediction models of BRCA1 or BRCA2 

mutation in breast/ovarian families attending 

familial cancer clinics. J Med Genet 

2003;40(7):503-10. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

209. Dearnaley DP, Kirby RS, Kirk D, et al. Diagnosis 

and management of early prostate cancer. Report 

of a British Association of Urological Surgeons 

Working Party. BJU Int 1999;83(1):18-33. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

210. Deligeoroglou E, Michailidis E, Creatsas G. Oral 

contraceptives and reproductive system cancer. 

Ann N Y Acad Sci 2003;997:199-208. 

Excluded: Not an eligible study design, OVIDEmbase. 

211. Desch CE, Benson AB, III, Somerfield MR, et al. 

Colorectal cancer surveillance: 2005 update of an 

American Society of Clinical Oncology practice 

guideline.[erratum appears in J Clin Oncol. 2006 

Mar 1;24(7):1224]. J Clin Oncol 

2005;23(33):8512-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

212. Dettenborn L, James GD, Berge-Landry H, et al. 

Heightened cortisol responses to daily stress in 

working women at familial risk for breast cancer. 

Biol Psychol 2005;69(2):167-79. 

Excluded: Not an eligible study design, OVIDMedline. 

213. Digianni LM, Kim HT, Emmons K, et al. 

Complementary medicine use among women 

enrolled in a genetic testing program. Cancer 

Epidemiol Biomarkers Prev 2003;12(4):321-6. 

Excluded: Not an eligible population, OVIDMedline. 

214. Digianni LM, Rue M, Emmons K, et al. 

Complementary medicine use before and 1 year 

following genetic testing for BRCA1/2 

mutations. Cancer Epidemiol Biomarkers Prev 

2006;15(1):70-5. 

Excluded: Not an eligible population, OVIDMedline. 

215. DiLorenzo TA, Schnur J, Montgomery GH, et al. 

A model of disease-specific worry in heritable 

disease: the influence of family history, perceived 

risk and worry about other illnesses. J Behav 

Med 2006;29(1):37-49. 

Excluded: Not an eligible study design, OVIDMedline. 

216. Dimella,L.F. The relationship between beliefs 

about god's control over health and adherence to 

breast cancer screening guidelines following 

genetic testing Dimella. 2003 

Excluded: Not an eligible intervention or 

outcome, OVID-PsycInfo. 

217. 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;104(9):1849-53. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

D-11
218. Driver JA, Gaziano JM, Gelber RP, et al. 

Development of a risk score for colorectal cancer 

in men. Am J Med 2007;120(3):257-63. 

PM:17349449 

Excluded: not an eligible study design, 

219. 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: Family history not systematically 

collected, OVID-Medline. 

220. Drossaert CHC, Boer H, Seydel ER. Prospective 

study on the determinants of repeat attendance 

and attendance patterns in breast cancer screening 

using the theory of planned behaviour. Psychol 

Health 2003;18(5):551-65. 

Excluded: Not an eligible study design, OVIDCinahl. 

221. DudokdeWit AC, Tibben A, Duivenvoorden HJ, 

et al. Distress in individuals facing predictive 

DNA testing for autosomal dominant late-onset 

disorders: comparing questionnaire results with 

in-depth interviews. Rotterdam/Leiden Genetics 

Workgroup. Am J Med Genet 1998;75(1):62-74. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

222. Duffy MJ, Bonfrer JM, Kulpa J, et al. CA125 in 

ovarian cancer: European Group on Tumor 

Markers guidelines for clinical use. Int J 

Gynecol Cancer 2005;15(5):679-91. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

223. Duffy MJ, van Dalen A, Haglund C, et al. 

Tumour markers in colorectal cancer: European 

Group on Tumour Markers (EGTM) guidelines 

for clinical use. Eur J Cancer 2007;43(9):1348-

60. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

224. Eastham JA, May R, Robertson JL, et al. 

Development of a nomogram that predicts the 

probability of a positive prostate biopsy in men 

with an abnormal digital rectal examination and a 

prostate-specific antigen between 0 and 4 ng/mL. 

Urology 1999;54(4):709-13. PM:10510933 

Excluded: Not an eligible study design 

225. Eccles DM, Evans DG, Mackay J. Guidelines for 

a genetic risk based approach to advising women 

with a family history of breast cancer. UK Cancer 

Family Study Group (UKCFSG). J Med Genet 

2000;37(3):203-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

226. Edwards A, Unigwe S, Elwyn G, et al. Effects of 

communicating individual risks in screening 

programmes: Cochrane systematic review. Br 

Med J 2003;327(7417):703-7. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

227. Edwards A, Gray J, Clarke A, et al. Interventions 

to improve risk communication in clinical 

genetics: Systematic review. Patient Educ Couns 

2008;71(1):4-25. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

228. Edwards AG, Evans R, Dundon J, et al. 

Personalised risk communication for informed 

decision making about taking screening tests. 

Cochrane Database Syst Rev 2006;(4):CD001865 

Excluded: Family history not systematically 

collected, OVID-Medline. 

229. Eisinger F, Tarpin C, Huiart L, et al. Behavioral 

and economic impact of a familial history of 

cancers. Fam Cancer 2005;4(4):307-11. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

230. Elit L. Familial ovarian cancer. Can Fam 

Physician 2001;47:778-84. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

231. Ellis P, Robinson P, Ciliska D, et al. A systematic 

review of studies evaluating diffusion and 

dissemination of selected cancer control 

interventions. Health Psychol 2005;24(5):488-

500. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

232. Elmore JG, Armstrong K, Lehman CD, et al. 

Screening for breast cancer. JAMA 

2005;293(10):1245-56. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

233. Emery J. The GRAIDS Trial: the development 

and evaluation of computer decision support for 

cancer genetic risk assessment in primary care. 

Ann Hum Biol 2005;32(2):218-27. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

234. 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;97(4):486-93. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

235. Engstrom PF, Benson AB, III, Chen YJ, et al. 

Colon cancer clinical practice guidelines in 

oncology. J Natl Compr Cancer Netw 

2005;3(4):468-91. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

236. Epstein SA, Lin TH, Audrain J, et al. Excessive 

breast self-examination among first-degree 

relatives of newly diagnosed breast cancer 

patients. High-Risk Breast Cancer Consortium. 

Psychosomatics 1997;38(3):253-61. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

237. Erblich J, Bovbjerg DH, Valdimarsdottir HB. 

Looking forward and back: distress among 

women at familial risk for breast cancer. Ann 

D-12
Behav Med 2000;22(1):53-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

238. Erlick RG, Rosen BP, Bradley LN, et al. 

Psychological impact of screening for familial 

ovarian cancer: reactions to initial assessment. 

Gynecol Oncol 1997;65(2):197-205. 

Excluded: Not an eligible population, OVIDMedline. 

239. Esplen MJ, Toner B, Hunter J, et al. A 

supportive-expressive group intervention for 

women with a family history of breast cancer: 

results of a phase II study. Psychooncology 

2000;9(3):243-52. 

Excluded: Not an eligible population, OVIDMedline. 

240. Esplen MJ, Hunter J, Leszcz M, et al. A 

multicenter study of supportive-expressive group 

therapy for women with BRCA1/BRCA2 

mutations. Cancer 2004;101(10):2327-40. 

Excluded: Not an eligible population, OVIDEmbase. 

241. Etminan M, FitzGerald JM, Gleave M, et al. 

Intake of selenium in the prevention of prostate 

cancer: a systematic review and meta-analysis. 

Cancer Causes Control 2005;16(9):1125-31. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

242. Euhus DM, Leitch AM, Huth JF, et al. 

Limitations of the Gail model in the specialized 

breast cancer risk assessment clinic. Breast J 

2002;8(1):23-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

243. Euhus DM, Smith KC, Robinson L, et al. Pretest 

prediction of BRCA1 or BRCA2 mutation by risk 

counselors and the computer model BRCAPRO. 

J Natl Cancer Inst 2002;94(11):844-51. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

244. Evans D, Lalloo F, Shenton A, et al. Uptake of 

screening and prevention in women at very high 

risk of breast cancer. Lancet 

2001;358(9285):889-90. 

Excluded: Not an eligible study design, OVIDMedline. 

245. Evans DG, Maher ER, Macleod R, et al. Uptake 

of genetic testing for cancer predisposition. J 

Med Genet 1997;34(9):746-8. 

Excluded: Not an eligible population, OVIDMedline. 

246. Evans DG, Eccles DM, Rahman N, et al. A new 

scoring system for the chances of identifying a 

BRCA1/2 mutation outperforms existing models 

including BRCAPRO. J Med Genet 

2004;41(6):474-80. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

247. Evans R, Edwards A, Brett J, et al. Reduction in 

uptake of PSA tests following decision aids: 

systematic review of current aids and their 

evaluations. Patient Educ Couns 2005;58(1):13-

26. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

248. Fabian CJ, Kimler BF. Selective estrogenreceptor modulators for primary prevention of 

breast cancer. J Clin Oncol 2005;23(8):1644-55. 

Excluded: Not an eligible study design, OVIDEmbase. 

249. Faccenda,K.A. Factors affecting the decision to 

have genetic testing for breast cancer Faccenda. 

1999 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

250. Fajardo LL. Screening mammography. Imaging 

Decisions MRI 2005;9(2):23-34. 

Excluded: Not an eligible study design, OVIDEmbase. 

251. Fang CY, Daly MB, Miller SM, et al. Coping 

with ovarian cancer risk: The moderating effects 

of perceived control on coping and adjustment. 

Br J Health Psychol 2006;11(4):561-80. 

Excluded: Not an eligible population, OVIDEmbase. 

252. Fasching PA, Bani MR, Nestle-Kramling C, et al. 

Evaluation of mathematical models for breast 

cancer risk assessment in routine clinical use. Eur 

J Cancer Prev 2007;16(3):216-24. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

253. Fernandez E, Vecchia CL, Balducci A, et al. Oral 

contraceptives and colorectal cancer risk: a metaanalysis. Br J Cancer 2001;84(5):722-7. 

Excluded: Not an eligible population, OVIDCochrane. 

254. Figueredo A, Rumble RB, Maroun J, et al. 

Follow-up of patients with curatively resected 

colorectal cancer: A practice guideline. BMC 

Cancer 2003;3:26 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

255. Finne P, Auvinen A, Aro J, et al. Estimation of 

prostate cancer risk on the basis of total and free 

prostate-specific antigen, prostate volume and 

digital rectal examination. Eur Urol 

2002;41(6):619-26. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cochrane. 

256. 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: Family history not systematically 

collected, OVID-Medline. 

257. Finney,L.J. Health beliefs, message framing, and 

mammography screening compliance: 

Measurement development and theory testing 

Finney. 2001 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

D-13
258. 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;12(2):120-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

259. Flamm CR, Ziegler KM, Aronson N. Technology 

evaluation center assessment synopsis: Use of 

magnetic resonance imaging to avoid a biopsy in 

women with suspicious primary breast lesions. J 

Am Coll Radiol 2005;2(6):485-7. 

Excluded: Not an eligible population, OVIDEmbase. 

260. Fletcher JW, Djulbegovic B, Soares HP, et al. 

Recommendations on the use of PET in 

oncology. J Nucl Med 2008;49(3):480-508. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

261. Fletcher KE, Clemow L, Peterson BA, et al. A 

path analysis of factors associated with distress 

among first-degree female relatives of women 

with breast cancer diagnosis. Health Psychol 

2006;25(3):413-24. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

262. Fletcher RH, Lobb R, Bauer MR, et al. Screening 

patients with a family history of colorectal 

cancer. J Gen Intern Med 2007;22(4):508-13. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

263. Fletcher SW, Elmore JG. Mammographic 

screening for breast cancer. N Engl J Med 

2003;348(17):1672-80. 

Excluded: Not an eligible study design, OVIDEmbase. 

264. Flook N. Colorectal cancer. Summary of 

Canadian screening guidelines. Can Fam 

Physician 2004;50:592-3. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

265. Flossmann E, Rothwell PM, British Doctors 

Aspirin Trial and the UK-TIA Aspirin Trial. 

Effect of aspirin on long-term risk of colorectal 

cancer: consistent evidence from randomised and 

observational studies. Lancet 

2007;369(9573):1603-13. 

Excluded: Not an eligible population, OVIDMedline. 

266. Fornasarig M, Viel A, Bidoli E, et al. Amsterdam 

criteria II and endometrial cancer index cases for 

an accurate selection of HNPCC families. Tumori 

2002;88(1):18-20. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

267. Frazier TG, Cummings PD. Motivational factors 

for participation in breast cancer screening. J 

Cancer Educ 1990;5(1):51-4. 

Excluded: Not an eligible study design, OVIDMedline. 

268. Friebel TM, Domchek SM, Neuhausen SL, et al. 

Bilateral prophylactic oophorectomy and bilateral 

prophylactic mastectomy in a prospective cohort 

of unaffected BRCA1 and BRCA2 mutation 

carriers. Clin Breast Cancer 2007;7(11):875-82. 

Excluded: Not an eligible population, OVIDEmbase. 

269. Friedman LC, Webb JA, Richards CS, et al. 

Psychological and behavioral factors associated 

with colorectal cancer screening among 

Ashkenazim. Prev Med 1999;29(2):119-25. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

270. Friedman LC, Everett TE, Peterson L, et al. 

Compliance with fecal occult blood test screening 

among low-income medical outpatients: a 

randomized controlled trial using a videotaped 

intervention. J Cancer Educ 2001;16(2):85-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

271. 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: Family history not systematically 

collected, OVID-Medline. 

272. Fries MH, Holt C, Carpenter I, et al. Diagnostic 

criteria for testing for BRCA1 and BRCA2: the 

experience of the Department of Defense 

Familial Breast/Ovarian Cancer Research Project. 

Mil Med 2002;167(2):99-103. 

Excluded: Model does not categorize risk or 

validate,OVID-Cinahl. 

273. Fries MH, Holt C, Carpenter I, et al. Guidelines 

for evaluation of patients at risk for inherited 

breast and ovarian cancer: recommendations of 

the Department of Defense Familial 

Breast/Ovarian Cancer Research Project. Mil 

Med 2002;167(2):93-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

274. Frost MH, Vockley CW, Suman VJ, et al. 

Perceived familial risk of cancer: Health concerns 

and psychosocial adjustment. J Psychosoc Oncol 

2000;18(1):63-82. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

275. Fuerst ML. Genetic testing plus Bethesda 

guidelines help screen for Lynch syndrome. 

Oncol Times 2005;27(18):13-4. 

Excluded: Not an eligible study design, OVIDCinahl. 

276. Fung MF, Bryson P, Johnston M, et al. Screening 

postmenopausal women for ovarian cancer: a 

systematic review. J Obstet Gynaecol Can 

2004;26(8):717-28. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

277. Furukawa T, Konishi F, Shitoh K, et al. 

Evaluation of screening strategy for detecting 

hereditary nonpolyposis colorectal carcinoma. 

Cancer 2002;94(4):911-20. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

D-14
278. Gagnon P, Massie MJ, Kash KM, et al. 

Perception of breast cancer risk and 

psychological distress in women attending a 

surveillance program. Psychooncology 

1996;5(3):259-69. 

Excluded: Family history not systematically 

collected, OVID-Cochrane. 

279. Gao X, LaValley MP, Tucker KL. Prospective 

studies of dairy product and calcium intakes and 

prostate cancer risk: a meta-analysis. J Natl 

Cancer Inst 2005;97(23):1768-77. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

280. Garrett MM, Fisher DA. Strategies to improve 

colorectal cancer screening rates. Journal of 

Clinical Outcomes Management 2006;13(9):512-

7. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

281. Gately ST. Targeting cyclooxygenase-2 for 

cancer prevention and treatment. Prog Drug Res 

2005;63:207-25. 

Excluded: Not an eligible study design, OVIDEmbase. 

282. Geelen A, Schouten JM, Kamphuis C, et al. Fish 

consumption, n-3 fatty acids, and colorectal 

cancer: a meta-analysis of prospective cohort 

studies. Am J Epidemiol 2007;166(10):1116-25. 

Excluded: Not an eligible population, OVIDMedline. 

283. Geirdal AO, Reichelt JG, Dahl AA, et al. 

Psychological distress in women at risk of 

hereditary breast/ovarian or HNPCC cancers in 

the absence of demonstrated mutations. Fam 

Cancer 2005;4(2):121-6. 

Excluded: Not an eligible population, OVIDMedline. 

284. Geirdal AO, Maehle L, Heimdal K, et al. Quality 

of life and its relation to cancer-related stress in 

women of families with hereditary cancer without 

demonstrated mutation. Qual Life Res 

2006;15(3):461-70. 

Excluded: Not an eligible study design, OVIDMedline. 

285. Geirdal AO, Dahl AA. The relationship between 

coping strategies and anxiety in women from 

families with familial breast-ovarian cancer in the 

absence of demonstrated mutations. 

Psychooncology 2008;17(1):49-57. 

Excluded: Not an eligible population, OVIDMedline. 

286. Geller G, Doksum T, Bernhardt BA, et al. 

Participation in breast cancer susceptibility 

testing protocols: influence of recruitment source, 

altruism, and family involvement on women's 

decisions. Cancer Epidemiol Biomarkers Prev 

1999;8(4:Pt 2):t-83 

Excluded: Not an eligible study design, OVIDMedline. 

287. Gerdes A-M, Cruger DG, Thomassen M, et al. 

Evaluation of two different models to predict 

BRCA1 and BRCA2 mutations in a cohort of 

Danish hereditary breast and/or ovarian cancer 

families. Clin Genet 2006;69(2):171-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

288. Giardiello FM, Brensinger JD, Petersen GM. 

AGA technical review on hereditary colorectal 

cancer and genetic testing. Gastroenterology 

2001;121(1):198-213. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

289. Giarelli E. Self-surveillance for genetic 

predisposition to cancer: behaviors and emotions. 

Oncol Nurs Forum 2006;Online.(2):221-31. 

Excluded: Not an eligible population, OVIDMedline. 

290. 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;12(8):821-7. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

291. Gil KM, von Gruenigen VE. Nutrition and 

ovarian carcinogenesis: A critical review. 

Women's Oncology Review 2005;5(2):81-94. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

292. Gilbar O. Women with high risk for breast 

cancer: psychological symptoms. Psychol Rep 

1997;80(3:Pt 1):t-2 

Excluded: Family history not systematically 

collected, OVID-Medline. 

293. Gilbar O. Coping with threat. Implications for 

women with a family history of breast cancer. 

Psychosomatics 1998;39(4):329-39. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

294. Gilpin CA, Carson N, Hunter AG. A preliminary 

validation of a family history assessment form to 

select women at risk for breast or ovarian cancer 

for referral to a genetics center. Clin Genet 

2000;58(4):299-308. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

295. Giuliano AE, Boolbol S, Degnim A, et al. Society 

of Surgical Oncology: Position statement on 

prophylactic mastectomy. Ann Surg Oncol 

2007;14(9):2425-7. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

296. Glicksman AS, Colorectal Cancer Care Task 

Force. Colorectal algorithm guidelines for 

screening. Med Health R I 2006;89(4):149 

Excluded: Not an eligible study design, OVIDMedline. 

297. Goelen G, Teugels E, Sermijn E, et al. 

Comparing the performance of family 

characteristics and predictive models for 

germline BRCA1/2 mutations in breast cancer 

families. Archives of Public Health 

2003;61(6):297-312. 

D-15
Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

298. Gologan A, Krasinskas A, Hunt J, et al. 

Performance of the revised Bethesda guidelines 

for identification of colorectal carcinomas with a 

high level of microsatellite instability. Arch 

Pathol Lab Med 2005;129(11):1390-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

299. Gonzalez-Perez A, Garcia Rodriguez LA, LopezRidaura R. Effects of non-steroidal antiinflammatory drugs on cancer sites other than the 

colon and rectum: a meta-analysis. BMC Cancer 

2003;3:28 

Excluded: Not an eligible population, OVIDMedline. 

300. Gorham ED, Garland CF, Garland FC, et al. 

Optimal vitamin D status for colorectal cancer 

prevention: a quantitative meta analysis. Am J 

Prev Med 2007;32(3):210-6. 

Excluded: Not an eligible population, VIDMedline. 

301. Gorin SS, Albert SM. The meaning of risk to first 

degree relatives of women with breast cancer. 

Women Health 2003;37(3):97-114. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

302. Goyal S, Bennett P, Sweetland HM, et al. Are 

surgeons effective counsellors for women with a 

family history of breast cancer? Eur J Surg 

Oncol 2002;28(5):501-4. 

Excluded: Not an eligible study design, VIDMedline. 

303. Gradishar WJ, Cella D. Selective estrogen 

receptor modulators and prevention of invasive 

breast cancer. JAMA 2006;295(23):2784-6. 

Excluded: Not an eligible study design, OVIDEmbase. 

304. 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;7(9):640-5. 

Excluded: Not an eligible study design, OVIDMedline. 

305. Gramling R, Anthony D, Frierson G, et al. The 

cancer worry chart: a single-item screening 

measure of worry about developing breast cancer. 

Psychooncology 2007;16(6):593-7. 

Excluded: Not an eligible population, OVIDMedline. 

306. Greco K, Nail L, Kendall J, et al. Breast cancer 

screening decisions in older high-risk women. 

Oncol Nurs Forum 2007;34(1):205 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

307. Greco,K.E. Mammography decision-making in 

women age 65 or older with a family history of 

breast cancer. 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

308. Green BB, Taplin SH. Breast cancer screening 

controversies. J Am Board Fam Pract 

2003;16(3):233-41. 

Excluded: Not an eligible population, OVIDMedline. 

309. Green RC, McLaughlin JR, Younghusband HB. 

SISE matters: the sum of information on seventyyr-old equivalents measures pedigree information 

content when assessing the risk of HNPCC in a 

family. Familial Cancer 2005;4(2):169-75. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

310. Gronwald J, Byrski T, Huzarski T, et al. A 

survey of preventive measures among BRCA1 

mutation carriers from Poland. Clin Genet 

2007;71(2):153-7. 

Excluded: Not an eligible population, OVIDMedline. 

311. Gross CP, Filardo G, Singh HS, et al. The 

relation between projected breast cancer risk, 

perceived cancer risk, and mammography use: 

Results from the national health interview survey. 

J Gen Intern Med 2006;21(2):158-64. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

312. Gross RE. Utilization of Breast Cancer Anxiety 

Scale in women at high risk for breast cancer. 

18th Annual SGNO Symposium. J Gynecol 

Oncol Nurs 2001;11(1):24-5. 

Excluded: Not an eligible study design, OVIDCinahl. 

313. Grube BJ. Barriers to diagnosis and treatment of 

breast cancer in the older woman. J Am Coll Surg 

2006;202(3):495-508. 

Excluded: Not an eligible study design, OVIDEmbase. 

314. Guerrero-Preston R, Chan C, Vlahov D, et al. 

Previous cancer screening behavior as predictor 

of endoscopic colon cancer screening among 

women aged 50 and over, in NYC 2002. J 

Community Health 2008;33(1):10-21. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

315. Guevarra,J.S. Psychological distress, African 

American acculturation and family history of 

breast cancer: Effects on breast self-examination 

frequency Guevarra. 2000 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

316. Gullini S, Matarese V, Pezzoli A, et al. Screening 

colonoscopy in asymptomatic increased-risk 

subjects. Eur J Cancer Prev 2001;10(2):175-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

317. Haas JS, Kaplan CP, Des JG, et al. Perceived 

risk of breast cancer among women at average 

and increased risk. J Womens Health (Larchmt) 

2005;14(9):845-51. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

318. Hackshaw A. EUSOMA review of 

mammography screening. Ann Oncol 

D-16
2003;14(8):1193-5. 

Excluded: Not an eligible study design, OVIDMedline. 

319. Hadley DW, Jenkins J, Dimond E, et al. Genetic 

counseling and testing in families with hereditary 

nonpolyposis colorectal cancer. Arch Intern Med 

2003;163(5):573-82. 

Excluded: Not an eligible population, OVIDMedline. 

320. Hadley DW, Jenkins JF, Dimond E, et al. Colon 

cancer screening practices after genetic 

counseling and testing for hereditary 

nonpolyposis colorectal cancer. J Clin Oncol 

2004;22(1):39-44. 

Excluded: Not an eligible population, OVIDMedline. 

321. Hadley DW, Jenkins JF, Steinberg SM, et al. 

Perceptions of cancer risks and predictors of 

colon and endometrial cancer screening in 

women undergoing genetic testing for Lynch 

syndrome. J Clin Oncol 2008;26(6):948-54. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

322. Hagoel L, Dishon S, Almog R, et al. Proband 

family uptake of familial-genetic counselling. 

Psychooncology 2000;9(6):522-7. 

Excluded: Not an eligible population, OVIDMedline. 

323. Hailey BJ, Carter CL, Burnett DR. Breast cancer 

attitudes, knowledge, and screening behavior in 

women with and without a family history of 

breast cancer. Health Care Women Int 

2000;21(8):701-15. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

324. Halbert CH, Lynch H, Lynch J, et al. Colon 

cancer screening practices following genetic 

testing for hereditary nonpolyposis colon cancer 

(HNPCC) mutations. Arch Intern Med 

2004;164(17):1881-7. Excluded: Not an eligible 

population, OVID-Medline. 

325. Halbert CH, Brewster K, Collier A, et al. 

Recruiting African American women to 

participate in hereditary breast cancer research. J 

Clin Oncol 2005;23(31):7967-73. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

326. Halbert CH, Kessler L, Wileyto EP, et al. Breast 

cancer screening behaviors among African 

American women with a strong family history of 

breast cancer. Prev Med 2006;43(5):385-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

327. Halbert C, Kessler L, Collier A, et al. 

Psychological functioning in African American 

women at an increased risk of hereditary breast 

and ovarian cancer. Clin Genet 2005;68(3):222-7. 

Excluded: Not an eligible study design, OVIDMedline. 

328. Hall MJ, Neugut AI. Review: only women with 

specific family histories should be referred for 

counseling or evaluation for BRCA breast and 

ovarian cancer susceptibility. ACP J Club 

2006;144(2):37 

Excluded: Not an eligible study design, OVIDCinahl. 

329. Hallowell N, Jacobs I, Richards M, et al. 

Surveillance or surgery? A description of the 

factors that influence high risk premenopausal 

women's decisions about prophylactic 

oophorectomy. J Med Genet 2001;38(10):683-91. 

Excluded: Not an eligible study design, OVIDMedline. 

330. Hamann HA, Somers TJ, Smith AW, et al. 

Posttraumatic stress associated with cancer 

history and BRCA1/2 genetic testing. 

Psychosom Med 2005;67(5):766-72. 

Excluded: Not an eligible population, OVIDMedline. 

331. Hampton T. Breast cancer prevention strategies 

explored. JAMA 2006;295(18):2128-9. 

Excluded: Not an eligible study design, OVIDEmbase. 

332. Hannemann M, Fox R, James M. Ovarian cancer 

death reduction for women at high risk: workload 

implications for gynaecology services. J Obstet 

Gynaecol 2006;26(1):42-4. 

Excluded: Not an eligible study design, OVIDMedline. 

333. Harmon AL, Westerberg AL, Bond DS, et al. 

Cancer prevention among rural youth: building a 

"Bridge" to better health with genealogy. J 

Cancer Educ 2005;20(2):103-7. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

334. Harris L, Fritsche H, Mennel R, et al. American 

Society of Clinical Oncology 2007 update of 

recommendations for the use of tumor markers in 

breast cancer. J Clin Oncol 2007;25(33):5287-

312. Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

335. Haug U, Brenner H. New stool tests for 

colorectal cancer screening: a systematic review 

focusing on performance characteristics and 

practicalness. Int J Cancer 2005;117(2):169-76. 

Excluded: Not an eligible population, OVIDMedline. 

336. Hay JL, McCaul KD, Magnan RE. Does worry 

about breast cancer predict screening behaviors? 

A meta-analysis of the prospective evidence. 

Prev Med 2006;42(6):401-8. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

337. Heatley MK. Immunohistochemical and 

functional biomarkers of value in female genital 

tract lesions: A systematic review with statistical 

meta-analysis. Int J Gynecol Pathol 

2007;26(2):177-9. 

Excluded: Not an eligible study design, OVIDEmbase. 

D-17
338. Heikkila K, Ebrahim S, Lawlor DA. A systematic 

review of the association between circulating 

concentrations of C reactive protein and cancer. J 

Epidemiol Community Health 2007;61(9):824-

32. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

339. 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;17(1):74-82. 

Excluded: Not an eligible study design, OVIDMedline. 

340. Hendriks YMC, De Jong AE, Morreau H, et al. 

Diagnostic approach and management of Lynch 

syndrome (Hereditary Nonpolyposis Colorectal 

Carcinoma): A guide for clinicians. CA Cancer J 

Clin 2006;56(4):213-25. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

341. Hensley ML, Robson ME, Kauff ND, et al. Preand postmenopausal high-risk women undergoing 

screening for ovarian cancer: anxiety, risk 

perceptions, and quality of life. Gynecol Oncol 

2003;89(3):440-6. 

Excluded: Not an eligible study design, OVIDMedline. 

342. Herendeen JM, Lindley C. Use of NSAIDs for 

the chemoprevention of colorectal cancer. Ann 

Pharmacother 2003;37(11):1664-74. 

Excluded: Not an eligible study design, OVIDMedline. 

343. Heshka JT, Palleschi C, Howley H, et al. A 

systematic review of perceived risks, 

psychological and behavioral impacts of genetic 

testing. Genet Med 2008;10(1):19-32. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

344. Hill J, Hanstock Z, Lockwood B. Keeping cancer 

at bay the natural way. Pharmaceutical Journal 

2006;(7416):277-84. 

Excluded: Not an eligible study design, OVIDEmbase. 

345. Hirota WK, Zuckerman MJ, Adler DG, et al. 

ASGE guideline: The role of endoscopy in the 

surveillance of premalignant conditions of the 

upper GI tract. Gastrointest Endosc 

2006;63(4):570-80. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

346. 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: Not an eligible population, OVIDMedline. 

347. Ho SM, Ho JW, Chan CL, et al. Decisional 

consideration of hereditary colon cancer genetic 

test results among Hong Kong chinese adults. 

Cancer Epidemiol Biomarkers Prev 

2003;12(5):426-32. 

Excluded: Not an eligible population, OVIDMedline. 

348. Ho V, Yamal JM, Atkinson EN, et al. Predictors 

of breast and cervical screening in Vietnamese 

women in Harris County, Houston, Texas. 

Cancer Nurs 130;28(2):119-29. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

349. Hodgson SV, Bishop DT, Dunlop MG, et al. 

Suggested screening guidelines for familial 

colorectal cancer. J Med Screen 1995;2(1):45-51. 

Excluded: Not an eligible publication type, 

OVID-Medline. 

350. Hofferbert S, Worringen U, Backe J, et al. 

Simultaneous interdisciplinary counseling in 

German breast/ovarian cancer families: first 

experiences with patient perceptions, surveillance 

behavior and acceptance of genetic testing. Genet 

Couns 2000;11(2):127-46. 

Excluded: Not an eligible population, OVIDMedline. 

351. Holloway S, Porteous M, Cetnarskyj R, et al. 

Long-term attendance at follow-up of women 

assessed as being at increased risk of developing 

breast cancer in south-east Scotland. Community 

Genet 2007;10(4):252-60. 

Excluded: Not an eligible population, OVIDMedline. 

352. Horsman D, Wilson BJ, Avard D, et al. Clinical 

management recommendations for surveillance 

and risk-reduction strategies for hereditary breast 

and ovarian cancer among individuals carrying a 

deleterious BRCA1 or BRCA2 mutation. J Obstet 

Gynaecol Can 2007;29(1):45-60. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

353. Hoskins KF, Zwaagstra A, Ranz M. Validation of 

a tool for identifying women at high risk for 

hereditary breast cancer in population-based 

screening. Cancer 2006;107(8):1769-76. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

354. Houlston RS, Murday V, Harocopos C, et al. 

Screening and genetic counselling for relatives of 

patients with colorectal cancer in a family cancer 

clinic.[erratum appears in BMJ 1990 Sep 

1;301(6749):446]. BMJ 1990;301(6748):366-8. 

Excluded: Not an eligible study design, OVIDMedline. 

355. Hsia J, Kemper E, Kiefe C, et al. The importance 

of health insurance as a determinant of cancer 

screening: evidence from the Women's Health 

Initiative. Prev Med 2000;31(3):261-70. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

D-18
356. Hughes KS, Roche CA, Whitney T, et al. The 

management of women at high risk of 

experiencing hereditary breast and ovarian 

cancer: The lahey guidelines. Disease 

Management and Health Outcomes 

2000;7(4):201-15. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

357. Humpel N, Magee C, Jones SC. The impact of a 

cancer diagnosis on the health behaviors of 

cancer survivors and their family and friends. 

Support Care Cancer 2007;15(6):621-30. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

358. Humphrey LL, Helfand M, Chan BK. Review: 

Mammography reduces breast cancer mortality 

rates. Evid Based Med 2003;8(2):45 

Excluded: Not an eligible study design, OVIDEmbase. 

359. Hundt S, Haug U, Brenner H. Blood markers for 

early detection of colorectal cancer: A systematic 

review. Cancer Epidemiol Biomarkers Prev 

2007;16(10):1935-53. 

Excluded: Not an eligible population, OVIDEmbase. 

360. Hunter A, Humphries SE. Family history of 

breast cancer and cost of life assurance: a test 

case comparison of current UK industry practice. 

BMJ 2005;331(7530):1438-9. 

Excluded: Not an eligible study design, OVIDMedline. 

361. Hurt GJ, McQuellon RP, Michielutte R, et al. 

Risk assessment of first-degree relatives of 

women with breast cancer: a feasibility study. 

Oncol Nurs Forum 2001;28(7):1097-104. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

362. Husaini BA, Sherkat DE, Bragg R, et al. 

Predictors of breast cancer screening in a panel 

study of African American women. Women 

Health 2001;34(3):35-51. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

363. Hyman RB, Baker S, Ephraim R, et al. Health 

Belief Model variables as predictors of screening 

mammography utilization. J Behav Med 

1994;17(4):391-406. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

364. Iannuzzi-Sucich M, Kenny AM. Preventive 

medicine for older women: gynecologic 

screening guidelines. Fam Pract Recertif 

2004;26(6):53-60. 

Excluded: Not an eligible intervention or 

outcome, VID-Cinahl. 

365. Ingraham BA, Bragdon B, Nohe A. Molecular 

basis of the potential of vitamin D to prevent 

cancer. Curr Med Res Opin 2008;24(1):139-49. 

Excluded: Not an eligible study design, OVIDMedline. 

366. Irani S, Krevsky B. Colorectal cancer screening: 

Which tests, how often? Consultant 

2007;47(2):138-45. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

367. Irmejs A, Borosenko V, Melbarde-Gorkusa I, et 

al. Nationwide study of clinical and molecular 

features of hereditary non-polyposis colorectal 

cancer (HNPCC) in Latvia. Anticancer Res 

2007;27(1 B):653-8. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

368. Irwig L, Houssami N, van Vliet C. New 

technologies in screening for breast cancer: a 

systematic review of their accuracy. Br J Cancer 

2004;90(11):2118-22. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

369. Isaacs C, Peshkin BN, Schwartz M, et al. Breast 

and ovarian cancer screening practices in healthy 

women with a strong family history of breast or 

ovarian cancer. Breast Cancer Res Treat 

2002;71(2):103-12. 

Excluded: Not an eligible study design, OVIDMedline. 

370. Italian Review Team 2006. Systematic Literature 

Review Report. The Associations between Food, 

Nutrition and Physical Activity and the Risk of 

Ovarian Cancer and Underlying Mechanisms. 

World Cancer Research Fund/American Institute 

for Cancer Research, Food, Nutrition, Physical 

Activity, and the Prevention of Cancer: a Global 

Perspective. Washington, DC: AICR, 2007. 

Excluded: Not an eligible population 

371. Ito H, Matsuo K, Wakai K, et al. An intervention 

study of smoking cessation with feedback on 

genetic cancer susceptibility in Japan. Prev Med 

2006;42(2):102-8. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

372. Itzkowitz SH, Present DH, Binder V, et al. 

Consensus conference: Colorectal cancer 

screening and surveillance in inflammatory 

bowel disease. Inflamm Bowel Dis 

2005;11(3):314-21. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

373. Jacobi CE, Jonker MA, Nagelkerke NJ, et al. 

Prevalence of family histories of breast cancer in 

the general population and the incidence of 

related seeking of health care. J Med Genet 

2003;40(7):e83 

Excluded: Family history not systematically 

collected, OVID-Medline. 

374. Jacobs ET, Jiang R, Alberts DS, et al. Selenium 

and colorectal adenoma: results of a pooled 

analysis.[see comment]. J Natl Cancer Inst 

2004;96(22):1669-75. Excluded: Family history 

not systematically collected, OVID-Medline. 

D-19
375. Jacobsen PB, Lamonde LA, Honour M, et al. 

Relation of family history of prostate cancer to 

perceived vulnerability and screening behavior. 

Psychooncology 2004;13(2):80-5. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

376. James GD, Berge-Landry HH, Valdimarsdottir 

HB, et al. Urinary catecholamine levels in daily 

life are elevated in women at familial risk of 

breast cancer. Psychoneuroendocrinology 

2004;29(7):831-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

377. James TM, Greiner KA, Ellerbeck EF, et al. 

Disparities in colorectal cancer screening: a 

guideline-based analysis of adherence. Ethn Dis 

2006;16(1):228-33. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

378. Janda M, Obermair A, Haidinger G, et al. 

Austrian women's attitudes toward and 

knowledge of breast self-examination. J Cancer 

Educ 2000;15(2):91-4. 

Excluded: Not an eligible study design, VIDCinahl. 

379. Jasperson KW, Lowstuter K, Weitzel JN. 

Assessing the predictive accuracy of hMLH1 and 

hMSH2 mutation probability models. J Genet 

Couns 2006;15(5):339-47. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

380. Jeffery, M, Hickey, et al. Follow-up strategies for 

patients treated for non-metastatic colorectal 

cancer. Cochrane Database Syst Rev 2008;(1): 

Excluded: Not an eligible intervention or 

outcome, OVID-Cochrane. 

381. Johnson KA, Trimbath JD, Petersen GM, et al. 

Impact of genetic counseling and testing on 

colorectal cancer screening behavior. Genet Test 

2002;6(4):303-6. 

Excluded: Not an eligible population, OVIDMedline. 

382. Johnson PM, Gallinger S, McLeod RS. 

Surveillance colonoscopy in individuals at risk 

for hereditary nonpolyposis colorectal cancer: an 

evidence-based review. Dis Colon Rectum 

1994;49(1):80-93. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

383. Joint Test and Technology Transfer Committee 

Working Group ACoMG. Genetic testing for 

colon cancer: joint statement of the American 

College of Medical Genetics and American 

Society of Human Genetics. Joint Test and 

Technology Transfer Committee Working Group. 

Genet Med 2000;2(6):362-6. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

384. Jones JL, Hughes KS, Kopans DB, et al. 

Evaluation of hereditary risk in a mammography 

population. Clin Breast Cancer 2005;6(1):38-44. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

385. Jordan SJ, Whiteman DC, Purdie DM, et al. Does 

smoking increase risk of ovarian cancer? A 

systematic review. Gynecol Oncol 

2006;103(3):1122-9. 

Excluded: Not an eligible population, OVIDMedline. 

386. Julian-Reynier C, Sobol H, Sevilla C, et al. 

Uptake of hereditary breast/ovarian cancer 

genetic testing in a French national sample of 

BRCA1 families.The French Cancer Genetic 

Network. Psychooncology 2000;9(6):504-10. 

Excluded: Not an eligible study design, OVIDMedline. 

387. Kadison P, Pelletier EM, Mounib EL, et al. 

Improved screening for breast cancer associated 

with a telephone-based risk assessment. Prev 

Med 1998;27(3):493-501. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

388. Kamidono S, Ohshima S, Hirao Y, et al. 

Evidence-based clinical practice guidelines for 

prostate cancer (summary - JUA 2006 edition). 

Int J Urol 2008;15(1):1-18. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

389. Kang HH, Williams R, Leary J, et al. Evaluation 

of models to predict BRCA germline mutations. 

Br J Cancer 2006;95(7):914-20. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

390. Kanik EA, Canbaz H, Colak T, et al. 

Chemopreventive effect of nonsteroidal antiinflammatory drugs on the development of a new 

colorectal polyp or adenoma in a high-risk 

population: A meta-analysis. Current Therapeutic 

Research - Clinical and Experimental 

2004;65(4):345-52. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

391. Kaplan KM, Weinberg GB, Small A, et al. Breast 

cancer screening among relatives of women with 

breast cancer. Am J Public Health 

1991;81(9):1174-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

392. Karazanashvili G, Abrahamsson PA. Prostate 

specific antigen and human glandular kallikrein 2 

in early detection of prostate cancer. J Urol 

2003;169(2):445-57. Excluded: Not an eligible 

study design, OVID-Medline. 

393. Karliner LS, Napoles-Springer A, Kerlikowske 

K, et al. Missed opportunities: family history and 

behavioral risk factors in breast cancer risk 

assessment among a multiethnic group of 

women. J Gen Intern Med 2007;22(3):308-14. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

D-20
394. Kash KM, Holland JC, Halper MS, et al. 

sychological distress and surveillance behaviors 

of women with a family history of breast cancer. 

J Natl Cancer Inst 1992;84(1):24-30. 

Excluded: Not an eligible study design, OVIDMedline. 

395. Kash KM, Holland JC, Osborne MP, et al. 

Psychological counseling strategies for women at 

risk of breast cancer. J Natl Cancer Inst 

1995;Monographs.(17):73-9. 

Excluded: Not an eligible publication type, 

OVID-Medline. 

396. Kataja VV, Bergh J. ESMO Minimum Clinical 

Recommendations for diagnosis, treatment and 

follow-up of prostate cancer. Ann Oncol 

2005;16:Suppl-6 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

397. Kataja VV, Colleoni M, Bergh J, et al. ESMO 

Minimum Clinical Recommendations for 

diagnosis, treatment and follow-up of locally 

recurrent or metastatic breast cancer (MBC). Ann 

Oncol 2005;16:Suppl-2 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

398. Katapodi MC, Lee KA, Facione NC, et al. 

Predictors of perceived breast cancer risk and the 

relation between perceived risk and breast cancer 

screening: a meta-analytic review. Prev Med 

2004;38(4):388-402. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

399. Katki HA. Effect of misreported family history 

on Mendelian mutation prediction models. 

Biometrics 2006;62(2):478-87. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

400. Katki HA. Incorporating medical interventions 

into carrier probability estimation for genetic 

counseling. BMC Medical Genetics 2007;8:13 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

401. Kaur JS, Roubidoux MA, Sloan J, et al. Can the 

Gail model be useful in American Indian and 

Alaska Native populations? Cancer 

2004;100(5):906-12. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

402. Kavanaugh CJ, Trumbo PR, Ellwood KC. The 

U.S. food and drug administration's evidencebased review for qualified health claims: 

Tomatoes, lycopene, and cancer. J Natl Cancer 

Inst 2007;99(14):1074-85. 

Excluded: Not an eligible population, OVIDEmbase. 

403. Keinan-Boker L, Baron-Epel O, Garty N, et al. 

Family history of breast cancer and compliance 

with mammography in Israel: findings of the 

National Health Survey 2003-2004 (EUROHIS). 

Eur J Cancer Prev 2007;16(1):43-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

404. Keller M, Jost R, Haunstetter CM, et al. 

Comprehensive genetic counseling for families at 

risk for HNPCC: impact on distress and 

perceptions. Genet Test 2002;6(4):291-302. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

405. Kelly K, Leventhal H, Toppmeyer D, et al. 

Subjective and objective risks of carrying a 

BRCA1/2 mutation in individuals of Ashkenazi 

Jewish descent. J Genetic Couns 2003;12(4):351-

71. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

406. Kelly K, Leventhal H, Andrykowski M, et al. 

The decision to test in women receiving genetic 

counseling for BRCA1 and BRCA2 mutations. J 

Genetic Couns 2004;13(3):237-57. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

407. Kelly,K.M. Subjective and objective risk in 

individuals testing for BRCA1 and BRCA2 

mutations Kelly. 2000 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

408. Kelly RB, Shank JC. Adherence to screening 

flexible sigmoidoscopy in asymptomatic patients. 

Med Care 1992;30(11):1029-42. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

409. Kenen R, Ardern-Jones A, Eeles R. Living with 

chronic risk: Healthy women with a family 

history of breast/ovarian cancer. ealth, Risk and 

Society 2003;5(3):315-31. 

Excluded: Not an eligible study design, OVIDEmbase. 

410. Kerber RA, Neklason DW, Samowitz WS, et al. 

Frequency of familial colon cancer and hereditary 

nonpolyposis colorectal cancer (Lynch 

syndrome) in a large population database. Fam 

Cancer 2005;4(3):239-44. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

411. Key J, Hodgson S, Omar RZ, et al. Meta-analysis 

of studies of alcohol and breast cancer with 

consideration of the methodological issues. 

Cancer Causes Control 2006;17(6):759-70. 

Excluded: Not an eligible population, OVIDMedline. 

412. Key TJ, Spencer EA.Carbohydrates and cancer: 

an overview of the epidemiological evidence. Eur 

J Clin Nutr 2007;61:Suppl-21 

Excluded: Not an eligible study design, OVIDMedline. 

413. Khan NF, Ward A, Watson E, et al. Long-term 

survivors of adult cancers and uptake of primary 

health services: A systematic review. Eur J 

Cancer 2008;44(2):195-204. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

414. Khatcheressian JL, Wolff AC, Smith TJ, et al. 

American Society of Clinical Oncology 2006 

update of the breast cancer follow-up and 

D-21
management guidelines in the adjuvant setting. J 

Clin Oncol 2006;24(31):5091-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

415. Kievit W, de Bruin JH, Adang EM, et al. Current 

clinical selection strategies for identification of 

hereditary non-polyposis colorectal cancer 

families are inadequate: a meta-analysis. Clin 

Genet 2004;65(4):308-16. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

416. Kim SE, Perez-Stable EJ, Wong S, et al. 

Association between cancer risk perception and 

screening behavior among diverse women. Arch 

Intern Med 2008;168(7):728-34. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

417. Kim Y, Valdimarsdottir HB, Bovbjerg DH. 

Family histories of breast cancer, coping styles, 

and psychological adjustment. J Behav Med 

2003;26(3):225-43. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

418. Kim Y, Duhamel KN, Valdimarsdottir HB, et al. 

Psychological distress among healthy women 

with family histories of breast cancer: effects of 

recent life events. Psychooncology 

2005;14(7):555-63. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

419. Kinney AY, Choi YA, DeVellis B, et al. Interest 

in genetic testing among first-degree relatives of 

colorectal cancer patients. Am J Prev Med 

2000;18(3):249-52. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

420. Kinney AY, Simonsen SE, Baty BJ, et al. Risk 

reduction behaviors and provider communication 

following genetic counseling and BRCA1 

mutation testing in an African American kindred. 

J Genetic Couns 2006;15(4):293-305. 

Excluded: Not an eligible population, OVIDMedline. 

421. Kinney AY, Hicken B, Simonsen SE, et al. 

Colorectal cancer surveillance behaviors among 

members of typical and attenuated FAP families. 

Am J Gastroenterol 2007;102(1):153-62. 

Excluded: Not an eligible study design, OVIDMedline. 

422. Klimberg VS, Galandiuk S, Singletary ES, et al. 

Society of Surgical Oncology: statement on 

genetic testing for cancer susceptibilty. 

Committee on Issues and Governmental Affairs 

of the Society of Surgical Oncology. Ann Surg 

Oncol 1999;6(5):507-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

423. Ko C, Hyman NH, Standards Committee of The 

American Society of Colon and Rectal Surgeons. 

Practice parameter for the detection of colorectal 

neoplasms: an interim report (revised). Dis Colon 

Rectum 2006;49(3):299-301. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

424. Kokuer M, Naguib RN, Jancovic P, et al. Cancer 

risk analysis in families with hereditary 

nonpolyposis colorectal cancer. IEEE Trans Inf 

Technol Biomed 2006;10(3):581-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

425. Koo BC, Ng CS, King-Im J, et al. Minimal 

preparation CT for the diagnosis of suspected 

colorectal cancer in the frail and elderly patient. 

Clin Radiol 2006;61(2):127-39. 

Excluded: Not an eligible population, OVIDEmbase. 

426. Koushik A, Hunter DJ, Spiegelman D, et al. 

Fruits, vegetables, and colon cancer risk in a 

pooled analysis of 14 cohort studies. J Natl 

Cancer Inst 2007;99(19):1471-83. 

Excluded: Not an eligible population, OVIDMedline. 

427. Kubik-Huch RA. Imaging the young breast. 

Breast 2006;15(Suppl 2):S35-S40 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

428. Kubo A, Corley DA. Meta-analysis of 

antioxidant intake and the risk of esophageal and 

gastric cardia adenocarcinoma. Am J 

Gastroenterol 2007;102(10):2323-30. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

429. Kuhl CK. Screening of women with hereditary 

risk of breast cancer. Clin Breast Cancer 

2004;5(4):269-71. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

430. Kumar AS, Esserman LJ. Statins: Healthpromoting agents show promise for breast cancer 

prevention. Clin Breast Cancer 2005;6(5):455-9. 

Excluded: Not an eligible study design, OVIDEmbase. 

431. Kuschel B, Hauenstein E, Kiechle M, et al. 

Hereditary breast and ovarian cancer - Current 

clinical guidelines in Germany. Breast Care 

2006;1(1):8-14. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

432. Lagerros YT, Hsieh S-F, Hsieh C-C. Physical 

activity in adolescence and young adulthood and 

breast cancer risk: A quantitative review. Eur J 

Cancer Prev 2004;13(1):5-12. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

433. Lancaster DR. Development and psychometric 

testing of the coping with breast cancer threat 

instrument. J Nurs Meas 2004;12(1):33-46. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

434. Lancaster,D.R.N. Coping with appraised threat of 

breast cancer: primary prevention coping 

behaviors utilized by women at increased risk. 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

D-22
435. Lancaster JM, Powell CB, Kauff ND, et al. 

Society of Gynecologic Oncologists Education 

Committee statement on risk assessment for 

inherited gynecologic cancer predispositions. 

Gynecol Oncol 2007;107(2):159-62. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

436. Lane DS, Zapka J, Breen N, et al. A systems 

model of clinical preventive care: the case of 

breast cancer screening among older women. For 

the NCI Breast Cancer Screening Consortium. 

Prev Med 2000;31(5):481-93. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

437. Larsson SC, Wolk A. Meat consumption and risk 

of colorectal cancer: a meta-analysis of 

prospective studies. Int J Cancer 

2006;119(11):2657-64. 

Excluded: Not an eligible population, OVIDMedline. 

438. Larsson SC, Giovannucci E, Wolk A. Folate and 

risk of breast cancer: a meta-analysis. J Natl 

Cancer Inst 2007;99(1):64-76. 

Excluded: Not an eligible population, OVIDMedline. 

439. Lauver D, Nabholz S, Scott K, et al. Testing 

theoretical explanations of mammography use. 

Nurs Res 1997;46(1):32-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

440. Lawlor DA, Juni P, Ebrahim S, et al. Systematic 

review of the epidemiologic and trial evidence of 

an association between antidepressant medication 

and breast cancer. J Clin Epidemiol 

2003;56(2):155-63. 

Excluded: Not an eligible population, OVIDEmbase. 

441. Leddin D, Hunt R, Champion M, et al. Canadian 

Association of Gastroenterology and the 

Canadian Digestive Health Foundation: 

Guidelines on colon cancer screening. Can J 

Gastroenterol 2004;18(2):93-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

442. Lee-Lin F, Menon U, Pett M, et al. Breast cancer 

beliefs and mammography screening practices 

among Chinese American immigrants. J Obstet 

Gynecol Neonatal Nurs 2007;36(3):212-21. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

443. Lee-Lin,F.F. Mammography and Pap testing 

screening among first generation Chinese 

Americans DIssertation Abstract. 2006 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

444. 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;27(5):400-6. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

445. Lee JR, Vogel VG. Who uses screening 

mammography regularly? Cancer Epidemiol 

Biomarkers Prev 1995;4(8):901-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

446. Lee R, Localio AR, Armstrong K, et al. A metaanalysis of the performance characteristics of the 

free prostate-specific antigen test. Urology 

2006;67(4):762-8. 

Excluded: Not an eligible population, OVIDMedline. 

447. Lee SC, Bernhardt BA, Helzlsouer KJ. 

Utilization of BRCA1/2 genetic testing in the 

clinical setting: report from a single institution. 

Cancer 2002;94(6):1876-85. 

Excluded: Not an eligible population, OVIDMedline. 

448. Legg JS. Genetic testing for inheritable cancers. 

Radiat Therapist 2004;13(2):99-105. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

449. 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;319(7212):757-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

450. Lemon S, Zapka J, Puleo E, et al. Colorectal 

cancer screening participation: comparisons with 

mammography and prostate-specific antigen 

screening. Am J Public Health 2001;91(8):1264-

72. Excluded: Family history not systematically 

collected, OVID-Medline. 

451. Lemon SC, Zapka JG, Clemow L. Health 

behavior change among women with recent 

familial diagnosis of breast cancer. Prev Med 

2004;39(2):253-62. Excluded: Family history not 

systematically collected, OVID-Medline. 

452. Lerman C, Rimer B, Trock B, et al. Factors 

associated with repeat adherence to breast cancer 

screening. Prev Med 1990;19(3):279-90. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

453. Lerman C, Daly M, Sands C, et al. 

Mammography adherence and psychological 

distress among women at risk for breast cancer. 

Natl Cancer Inst 1993;85(13):1074-80. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

454. Lerman C, Kash K, Stefanek M. Younger women 

at increased risk for breast cancer: perceived risk, 

psychological well-being, and surveillance 

behavior. J Natl Cancer Inst 

1994;Monographs.(16):171-6. 

Excluded: Not an eligible publication type, 

OVID-Medline. 

455. Lerman C, Narod S, Schulman K, et al. BRCA1 

testing in families with hereditary breast-ovarian 

cancer. A prospective study of patient decision 

making and outcomes. JAMA 

1996;275(24):1885-92. Excluded: Family history 

not systematically collected, OVID-Medline. 

D-23
456. Lerman C, Schwartz MD, Miller SM, et al. A 

randomized trial of breast cancer risk counseling: 

interacting effects of counseling, educational 

level, and coping style. Health Psychol 

1996;15(2):75-83. 

Excluded: Not an eligible population, OVIDMedline. 

457. Lerman C, Schwartz MD, Lin TH, et al. The 

influence of psychological distress on use of 

genetic testing for cancer risk. J Consult Clin 

Psychol 1997;65(3):414-20. 

Excluded: Not an eligible population, OVIDMedline. 

458. Lerman C, Hughes C, Trock BJ, et al. Genetic 

testing in families with hereditary nonpolyposis 

colon cancer. JAMA 1999;281(17):1618-22. 

Excluded: Not an eligible study design, OVIDMedline. 

459. Lerman C, Hughes C, Croyle RT, et al. 

Prophylactic surgery decisions and surveillance 

practices one year following BRCA1/2 testing. 

Prev Med 2000;31(1):75-80. 

Excluded: Not an eligible population, OVIDMedline. 

460. Lesniak,K.T. Psychological and 

sociodemographic predictors of psychological 

distress in BRCA1 and BRAC2 genetic testing 

participants within a community based genetic 

screening program Lesniak. 2001 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

461. Levin B, Barthel JS, Burt RW, et al. Colorectal 

Cancer Screening Clinical Practice Guidelines. J 

Natl Compr Cancer Netw 2006;4(4):384-420. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

462. Levin B, Lieberman DA, McFarland B, et al. 

Screening and surveillance for the early detection 

of colorectal cancer and adenomatous polyps, 

2008: a joint guideline from the American Cancer 

Society, the US Multi-Society Task Force on 

Colorectal Cancer, and the American College of 

Radiology. Gastroenterology 2008;134(5):1570-

95. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

463. Levin TR, Farraye FA, Schoen RE, et al. Quality 

in the technical performance of screening flexible 

sigmoidoscopy: Recommendations of an 

international multi-society task group. Gut 

2005;54(6):807-13. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

464. Levine M, Moutquin JM, Walton R, et al. 

Chemoprevention of breast cancer. A joint 

guideline from the Canadian Task Force on 

Preventive Health Care and the Canadian Breast 

Cancer Initiative's Steering Committee on 

Clinical Practice Guidelines for the Care and 

Treatment of Breast Cancer. CMAJ 

2001;164(12):1681-90. 

Excluded: Model does not categorize risk or 

validate, VID-Medline. 

465. Levy BT, Dawson J, Hartz AJ, et al. Colorectal 

cancer testing among patients cared for by Iowa 

family physicians. Am J Prev Med 

2006;31(3):193-201. 

Excluded: Not an eligible study design, OVIDMedline. 

466. Lewis JD, Ng K, Hung KE, et al. Detection of 

proximal adenomatous polyps with screening 

sigmoidoscopy: a systematic review and metaanalysis of screening colonoscopy. Arch Intern 

Med 2003;163(4):413-20. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

467. Lewis SJ, Harbord RM, Harris R, et al. Metaanalyses of observational and genetic association 

studies of folate intakes or levels and breast 

cancer risk. J Natl Cancer Inst 2006;98(22):1607-

22. 

Excluded: Not an eligible population, OVIDMedline. 

468. Liberman M, Sampalis F, Mulder DS, et al. 

Breast cancer diagnosis by scintimammography: 

a meta-analysis and review of the literature. 

Breast Cancer Res Treat 2003;80(1):115-26. 

Excluded: Not an eligible population, OVIDMedline. 

469. Liede A, Metcalfe K, Hanna D, et al. Evaluation 

of the needs of male carriers of mutations in 

BRCA1 or BRCA2 who have undergone genetic 

counseling. Am J Hum Genet 2000;67(6):1494-

504. 

Excluded: Not an eligible population, OVIDMedline. 

470. Lim J, Macluran M, Price M, et al. Short- and 

long-term impact of receiving genetic mutation 

results in women at increased risk for hereditary 

breast cancer. J Genet Couns 2004;13(2):115-33. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

471. Lin, O, Roy, et al. Screening sigmoidoscopy and 

colonoscopy for reducing colorectal cancer 

mortality in asymtomatic persons. Cochrane 

Database Syst Rev 2008;(1): 

Excluded: Not an eligible study design, OVIDCochrane. 

472. Lin CJ, Block B, Nowalk MP, et al. Breast cancer 

risk assessment in socioeconomically 

disadvantaged urban communities. J Natl Med 

Assoc 2007;99(7):752-6. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

473. Lin OS. Clinical update: postpolypectomy 

colonoscopy surveillance. Lancet 

2007;370(9600):1674-6. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

D-24
474. Lindberg NM, Wellisch D. Anxiety and 

compliance among women at high risk for breast 

cancer. Ann Behav Med 2001;23(4):298-303. 

Excluded: Not an eligible study design, OVIDMedline. 

475. Lindberg NM, Wellisch DK. Identification of 

traumatic stress reactions in women at increased 

risk for breast cancer. Psychosomatics 

2004;45(1):7-16. 

Excluded: Not an eligible study design, OVIDMedline. 

476. Lindor NM, Petersen GM, Hadley DW, et al. 

Recommendations for the care of individuals 

with an inherited predisposition to Lynch 

syndrome: a systematic review. JAMA 

2006;296(12):1507-17. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

477. 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. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

478. Lipton LR, Johnson V, Cummings C, et al. 

Refining the Amsterdam Criteria and Bethesda 

Guidelines: testing algorithms for the prediction 

of mismatch repair mutation status in the familial 

cancer clinic.[erratum appears in J Clin Oncol. 

2005 May 20;23(15):3652]. J Clin Oncol 

2004;22(24):4934-43. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

479. Lise M, Zavagno G, Meggiolaro F. Prophylactic 

mastectomy in women at high risk of breast 

cancer. FORUM - Trends in Experimental and 

Clinical Medicine 1997;7(1 Suppl. 2):112-6. 

Excluded: Not an eligible study design, OVIDEmbase. 

480. Little MP, Muirhead CR, Charles MW. 

Describing time and age variations in the risk of 

radiation-induced solid tumour incidence in the 

Japanese atomic bomb survivors using 

generalized relative and absolute risk models. 

Stat Med 1999;18(1):17-33. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

481. Liu M, Guo Y-M, Guo X-J, et al. Evaluation of 

scintimammorgraphy in the diagnosis of primary 

breast cancer: A meta-analysis. Chinese Journal 

of Evidence-Based Medicine 2005;5(7):536-42. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

482. Liu X, Sennett C, Legorreta AP. Mammography 

utilization among California women age 40-49 in 

a managed care environment. Breast Cancer Res 

Treat 2001;67(2):181-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

483. Loader S, Shields C, Rowley PT. Impact of 

genetic counseling and DNA testing on 

individuals with colorectal cancer with a positive 

family history: a population-based study. Genet 

Test 2005;9(4):313-9. 

Excluded: Not an eligible population, OVIDMedline. 

484. Locker GY, Hamilton S, Harris J, et al. ASCO 

2006 update of recommendations for the use of 

tumor markers in gastrointestinal cancer. J Clin 

Oncol 2006;24(33):5313-27. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

485. Lodder L, Frets PG, Trijsburg RW, et al. 

Attitudes and distress levels in women at risk to 

carry a BRCA1/BRCA2 gene mutation who 

decline genetic testing. Am J Med Genet 

2003;(Part 3):266-72. 

Excluded: Not an eligible study design, OVIDMedline. 

486. Loescher LJ. Cancer worry in women with 

hereditary risk factors for breast cancer. Oncol 

Nurs Forum 2003;Online.(5):767-72. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

487. Loescher LJ, Lim K, Leitner O, et al. Risk 

control behaviors following BRCA genetic 

predisposition testing. Oncol Nurs Forum 

2007;34(1):226 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

488. Longacre AV, Cramer LD, Gross CP. Screening 

colonoscopy use among individuals at higher 

colorectal cancer risk. J Clin Gastroenterol 

2006;40(6):490-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

489. Lopez ML, Iglesias JM, del Valle MO, et al. 

Impact of a primary care intervention on 

smoking, drinking, diet, weight, sun exposure, 

and work risk in families with cancer experience. 

Cancer Causes Control 2007;18(5):525-35. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

490. Lord SJ, Lei W, Craft P, et al. A systematic 

review of the effectiveness of magnetic resonance 

imaging (MRI) as an addition to mammography 

and ultrasound in screening young women at high 

risk of breast cancer. Eur J Cancer 

2007;43(13):1905-17. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

491. Lostumbo L, Carbine N, Wallace J, et al. 

Prophylactic mastectomy for the prevention of 

breast cancer. Cochrane Database Syst Rev 

2004;(4):CD002748 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

D-25
492. Love RR, Brown RL, Davis JE, et al. Frequency 

and determinants of screening for breast cancer in 

primary care group practice. Arch Intern Med 

1993;153(18):2113-7. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

493. Lubish L, Greenberg S, Friger M, et al. Breast 

cancer screening in two multicultural family 

practice teaching clinics. Isr Med Assoc J 

2001;3(8):579-83. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

494. Lunet N, Valbuena C, Vieira AL, et al. Fruit and 

vegetable consumption and gastric cancer by 

location and histological type: Case-control and 

meta-analysis. Eur J Cancer Prev 

2007;16(4):312-27. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

495. Lux MP, Ackermann S, Bani MR, et al. Age of 

uptake of early cancer detection facilities by lowrisk and high-risk patients with familial breast 

and ovarian cancer. Eur J Cancer Prev 

2005;14(6):503-11. 

Excluded: Not an eligible study design, OVIDMedline. 

496. Lux MP, Ackermann S, Nestle-Kramling C, et al. 

Use of intensified early cancer detection in highrisk patients with familial breast and ovarian 

cancer. Eur J Cancer Prev 2005;14(4):399-411. 

Excluded: Not an eligible population, OVIDMedline. 

497. Lynch HT, Snyder C, Lynch JF, et al. Patient 

responses to the disclosure of BRCA mutation 

tests in hereditary breast-ovarian cancer families. 

Cancer Genet Cytogenet 2006;165(2):91-7. 

Excluded: Not an eligible population, OVIDMedline. 

498. MacDonald DJ, Sarna L, Uman GC, et al. Cancer 

screening and risk-reducing behaviors of women 

seeking genetic cancer risk assessment for breast 

and ovarian cancers. Oncol Nurs Forum 

2006;Online.(2):E27-E35 

Excluded: Not an eligible population, OVIDMedline. 

499. MacInnis RJ, English DR. Body size and 

composition and prostate cancer risk: systematic 

review and meta-regression analysis. Cancer 

Causes Control 2006;17(8):989-1003. 

Excluded: Not an eligible population, OVIDMedline. 

500. Maciosek MV, Coffield AB, Edwards NM, et al. 

Priorities among effective clinical preventive 

services: results of a systematic review and 

analysis. Am J Prev Med 2006;31(1):52-61. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

501. MacKarem G, Roche CA, Hughes KS. The 

effectiveness of the Gail model in estimating risk 

for development of breast cancer in women under 

40 years of age. Breast J 2001;7(1):34-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

502. MacLean CH, Newberry SJ, Mojica WA, et al. 

Effects of omega-3 fatty acids on cancer risk: a 

systematic review. 2006 Apr 26;295(16):1900]. 

JAMA 2006;295(4):403-15. 

Excluded: Not an eligible population, OVIDMedline. 

503. Madalinska JB, Van Beurden M, Bleiker EM, et 

al. Predictors of prophylactic bilateral salpingooophorectomy compared with gynecologic 

screening use in BRCA1/2 mutation carriers. J 

Clin Oncol 2007;25(3):301-7. 

Excluded: Not an eligible population, OVIDCinahl. 

504. Madlensky L. Screening behaviors in relatives of 

Ontario colorectal cancer patients: a socialecological approach. 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

505. Madlensky L, Esplen MJ, Gallinger S, et al. 

Relatives of colorectal cancer patients: factors 

associated with screening behavior. Am J Prev 

Med 2003;25(3):187-94. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

506. 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;90(1):47-54. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

507. 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: Family history not systematically 

collected, OVID-Medline. 

508. Mahon SM, Casperson DS. Hereditary cancer 

syndrome: Part 2.--Psychosocial issues, concerns, 

and screening--results of a qualitative study. 

Oncol Nurs Forum 1995;22(5):775-82. 

Excluded: Not an eligible study design, OVIDMedline. 

509. Mahon SM. From research to clinical practice. 

Evidence-based practice: recommendations for 

the early detection of breast cancer. Clin J Oncol 

Nurs 2003;7(6):693-6. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

510. Mangiapane S, Blettner M, Schlattmann P. 

Aspirin use and breast cancer risk: A metaanalysis and meta-regression of observational 

studies from 2001 to 2005. Pharmacoepidemiol 

Drug Saf 2008;17(2):115-24. Excluded: Not an 

eligible population, OVID-Embase. 

D-26
511. Manheimer,J. Medical risk, perceived risk, and 

body anxiety in women attending a high-risk 

breast surveillance clinic Manheimer. 1993 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

512. Mann GJ, Thorne H, Balleine RL, et al. Analysis 

of cancer risk and BRCA1 and BRCA2 mutation 

prevalence in the kConFab familial breast cancer 

resource. Breast Cancer Res 2006;8(1):R12 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

513. Marques-Vidal P, Ravasco P, Ermelinda CM. 

Foodstuffs and colorectal cancer risk: a review. 

[Review] [66 refs]. Clin Nutr 2006;25(1):14-36. 

Excluded: Not an eligible population, OVIDMedline. 

514. Marroni F, Aretini P, D'Andrea E, et al. 

Penetrances of breast and ovarian cancer in a 

large series of families tested for BRCA1/2 

mutations. Eur J Hum Genet 2004;12(11):899-

906. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

515. Marroni F, Aretini P, D'Andrea E, et al. 

Evaluation of widely used models for predicting 

BRCA1 and BRCA2 mutations. J Med Genet 

2004;41(4):278-85. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

516. Marteau TM, Lerman C. Genetic risk and 

behavioural change. BMJ 2001;322(7293):1056-

9. 

Excluded: Not an eligible study design, OVIDEmbase. 

517. Martin RM, Middleton N, Gunnell D, et al. 

Breast-feeding and cancer: The Boyd Orr cohort 

and a systematic review with meta-analysis. J 

Natl Cancer Inst 2005;97(19):1446-57. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

518. Martin W, Degner L. Perception of risk and 

surveillance practices of women with a family 

history of breast cancer. Cancer Nurs 

2006;29(3):227-35. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

519. Masi CM, Blackman DJ, Peek ME. Interventions 

to enhance breast cancer screening, diagnosis, 

and treatment among racial and ethnic minority 

women. Med Care Res Rev 

2007;64(5:Suppl):Suppl-242S 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

520. Matthews BA, Nattinger AB, Venkatesan T, et al. 

Objective risk, subjective risk, and colorectal 

cancer screening among a clinic sample. Psychol 

Health Med 2007;12(2):135-47. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

521. Mayo MS, Kimler BF, Fabian CJ. Evaluation of 

models for the prediction of breast cancer 

development in women at high risk. J Appl Res 

2001;1(1):37-44. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

522. McCarthy BD, Moskowitz MA. Screening 

flexible sigmoidoscopy: Patient attitudes and 

compliance. J Gen Intern Med 1993;8(3):120-5. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

523. McCaul KD, Branstetter AD, O'Donnell SM, et 

al. A descriptive study of breast cancer worry. J 

Behav Med 1998;21(6):565-79. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

524. McCormack VA, dos SS, I. Breast density and 

parenchymal patterns as markers of breast cancer 

risk: a meta-analysis. Cancer Epidemiol 

Biomarkers Prev 2006;15(6):1159-69. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

525. McCullum M. Hereditary cancer risk assessment. 

Can Oncol Nurs J 1997;7(4):236-7. 

Excluded: Not an eligible study design, OVIDMedline. 

526. McDonald L. Soy food and soy supplements may 

not do the same thing in terms of breast cancer 

risk reduction. Cancer Biol Ther 2006;5(5):458-

9. 

Excluded: Not an eligible study design, OVIDEmbase. 

527. McInerney-Leo A, Hadley D, Kase RG, et al. 

BRCA1/2 testing in hereditary breast and ovarian 

cancer families III: risk perception and screening. 

Am J Med Genet 2006;(20):2198-206. 

Excluded: Not an eligible population, OVIDMedline. 

528. McKinley JM, Weideman PC, Jenkins MA, et al. 

Prostate screening uptake in Australian BRCA1 

and BRCA2 carriers. Hereditary Cancer in 

Clinical Practice 2007;5(3):161-3. 

Excluded: Not an eligible population, OVIDEmbase. 

529. McKinnon W, Naud S, Ashikaga T, et al. Results 

of an intervention for individuals and families 

with BRCA mutations: a model for providing 

medical updates and psychosocial support 

following genetic testing. J Genetic Couns 

2007;16(4):433-56. 

Excluded: Not an eligible population, OVIDMedline. 

530. McMurrick P, Dorien S, Shapiro J. Bowel cancer 

- guide for the GP. Aust Fam Physician 

2006;35(4):192-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

531. McTiernan A, Kuniyuki A, Yasui Y, et al. 

Comparisons of two breast cancer risk estimates 

in women with a family history of breast cancer. 

Cancer Epidemiol Biomarkers Prev 

2001;10(4):333-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

D-27
532. Meijers-Heijboer H, Brekelmans CT, MenkePluymers M, et al. Use of genetic testing and 

prophylactic mastectomy and oophorectomy in 

women with breast or ovarian cancer from 

families with a BRCA1 or BRCA2 mutation. J 

Clin Oncol 2003;21(9):1675-81. 

Excluded: Not an eligible population, OVIDMedline. 

533. Meiser B, Butow P, Barratt A, et al. Attitudes 

toward prophylactic oophorectomy and screening 

utilization in women at increased risk of 

developing hereditary breast/ovarian cancer. 

Gynecol Oncol 1999;75(1):122-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

534. Meiser B, Butow P, Barratt A, et al. Breast 

cancer screening uptake in women at increased 

risk of developing hereditary breast cancer. 

Breast Cancer Res Treat 2000;59(2):101-11. 

Excluded: Not an eligible study design, OVIDMedline. 

535. Meiser B, Butow P, Schnieden V, et al. 

Psychological adjustment of women at increased 

risk of developing hereditary breast cancer. 

Psychol Health Med 2000;5(4):377-88. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

536. Meiser B, Halliday JL. What is the impact of 

genetic counselling in women at increased risk of 

developing hereditary breast cancer? A metaanalytic review. Soc Sci Med 2002;54(10):1463-

70. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

537. Meiser B, Butow P, Price M, et al. Attitudes to 

prophylactic surgery and chemoprevention in 

Australian women at increased risk for breast 

cancer. J Womens Health (Larchmt) 

2003;12(8):769-78. 

Excluded: Not an eligible study design, OVIDMedline. 

538. Meiser B, Cowan R, Costello A, et al. Prostate 

cancer screening in men with a family history of 

prostate cancer: the role of partners in influencing 

men's screening uptake. Urology 2007;70(4):738-

42. Excluded: Not an eligible study design, 

OVID-Medline. 

539. Meiser B, Butow P, Schnieden V, et al. 

Psychological adjustment of women at increased 

risk of developing hereditary breast cancer. 

Psychol Health Med 2000;5(4):377-88. 

Excluded: Not an eligible population, OVIDPsycInfo. 

540. Menon U, Skates SJ, Lewis S, et al. Prevalence 

screening for ovarian cancer using risk of ovarian 

cancer algorithm. Int J Gynecol Cancer 

2003;13(suppl 1):1 Excluded: Not an eligible 

intervention or outcome, OVID-Cochrane. 

541. Menon U, Skates SJ, Lewis S, et al. Prospective 

study using the risk of ovarian cancer algorithm 

to screen for ovarian cancer. J Clin Oncol 

2005;23(31):7919-26. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cochrane. 

542. Mertens WC, Katz D, Quinlan M, et al. Effect of 

oncologist-based counseling on patient-perceived 

breast cancer risk and psychological distress. 

Community Oncology 2008;5(2):108-14. 

Excluded: Not an eligible population, OVIDEmbase. 

543. Metcalfe KA, Foulkes WD, Kim-Sing C, et al. 

Family history as a predictor of uptake of cancer 

preventive procedures by women with a BRCA1 

or BRCA2 mutation. Clin Genet 

2008;73(5):474-9. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

544. Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, 

et al. International variation in rates of uptake of 

preventive options in BRCA1 and BRCA2 

mutation carriers. Int J Cancer 2008;122(9):2017-

22. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

545. Miller D, Livingstone V, Herbison P. 

Interventions for relieving the pain and 

discomfort of screening mammography. 

Cochrane Database Syst Rev 2008;(1):CD002942 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

546. Mistry K, Cable G. Meta-analysis of prostatespecific antigen and digital rectal examination as 

screening tests for prostate carcinoma. J Am 

Board Fam Pract 2003;16(2):95-101. 

Excluded: Not an eligible population, OVIDMedline. 

547. Mizoue T, Tanaka K, Tsuji I, et al. Alcohol 

drinking and colorectal cancer risk: an evaluation 

based on a systematic review of epidemiologic 

evidence among the Japanese population. Jpn J 

Clin Oncol 2006;36(9):582-97. 

Excluded: Not an eligible population, OVIDMedline. 

548. Modan B, Hartge P, Hirsh-Yechezkel G, et al. 

Parity, oral contraceptives, and the risk of ovarian 

cancer among carriers and noncarriers of a 

BRCA1 or BRCA2 mutation. N Engl J Med 

2001;345(4):235-40. PM:11474660 

Excluded: Not an eligible study design 

549. Moghaddam AA, Woodward M, Huxley R. 

Obesity and risk of colorectal cancer: a metaanalysis of 31 studies with 70,000 events. Cancer 

Epidemiol Biomarkers Prev 2007;16(12):2533-

47. Excluded: Not an eligible population, OVIDMedline. 

550. Moja L, Moschetti I, Liberati A, et al. 

Understanding systematic reviews: the metaanalysis graph (also called 'forest plot'). Intern 

Emerg Med 2007;2(2):140-2. Excluded: Not an 

eligible study design, OVID-Medline. 

D-28
551. Moller P, Evans G, Haites N, et al. Guidelines 

for follow-up of women at high risk for inherited 

breast cancer: consensus statement from the 

Biomed 2 Demonstration Programme on 

Inherited Breast Cancer. Dis Markers 1999;15(1-

3):207-11. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

552. Moller P, Evans DG, Haites NE, et al. Women at 

risk for inherited breast or ovarian cancer: 

Guidelines for follow-up. CME Journal of 

Gynecologic Oncology 2000;5(3):269-71. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

553. Monninkhof EM, Elias SG, Vlems FA, et al. 

Physical activity and breast cancer: a systematic 

review. Epidemiology 2007;18(1):137-57. 

Excluded: Not an eligible population, OVIDMedline. 

554. Montgomery DA, Krupa K, Cooke TG. Followup in breast cancer: does routine clinical 

examination improve outcome? A systematic 

review of the literature. Br J Cancer 

2007;97(12):1632-41. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

555. Morantz C, American Cancer Society. ACS 

guidelines for early detection of cancer. Am Fam 

Physician 2004;69(8):2013 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

556. Morris KT, Johnson N, Krasikov N, et al. Genetic 

counseling impacts decision for prophylactic 

surgery for patients perceived to be at high risk 

for breast cancer. Am J Surg 2001;181(5):431-3. 

Excluded: Not an eligible population, OVIDMedline. 

557. Moskal A, Norat T, Ferrari P, et al. Alcohol 

intake and colorectal cancer risk: a dose-response 

meta-analysis of published cohort studies. Int J 

Cancer 2007;120(3):664-71. 

Excluded: Not an eligible population, OVIDMedline. 

558. Moss S. Overdiagnosis in randomised controlled 

trials of breast cancer screening. Breast Cancer 

Res 2005;7(5):230-4. 

Excluded: Not an eligible study design, OVIDEmbase. 

559. Mpofu C, Watson AJ, Rhodes JM. Strategies for 

detecting colon cancer and/or dysplasia in 

patients with inflammatory bowel disease.[update 

in Cochrane Database Syst Rev. 

2006;(2):CD000279; PMID: 16625534]. 

Cochrane Database Syst Rev 2004;(2):CD000279 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

560. Mulhall BP, Veerappan GR, Jackson JL. Metaanalysis: computed tomographic colonography. 

Summary for patients in Ann Intern Med. 2005 

Apr 19;142(8):I74; PMID: 15838063. Ann Intern 

Med 2005; Excluded: Not an eligible population, 

OVID-Medline. 

561. Murabito JM, Evans JC, Larson MG, et al. 

Family breast cancer history and mammography: 

Framingham Offspring Study. Am J Epidemiol 

2001;154(10):916-23. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

562. Murff HJ, Spigel DR, Syngal S. Does this patient 

have a family history of cancer? An evidencebased analysis of the accuracy of family cancer 

history. JAMA 2004;292(12):1480-9. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

563. Murff HJ, Peterson NB, Greevy RA, et al. Early 

initiation of colorectal cancer screening in 

individuals with affected first-degree relatives. J 

Gen Intern Med 2007;22(1):121-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

564. Murff HJ, Peterson NB, Fowke JH, et al. 

Colonoscopy screening in African Americans and 

whites with affected first-degree relatives. Arch 

Intern Med 2008;168(6):625-31. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

565. Myers,M.F. Decision making regarding 

prophylactic mastectomy and breast cancer 

susceptibility testing among women at increased 

risk of breast cancer. Dissertation Abstract. 2000 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

566. Myers RE, Weinberg DS, Manne SL, et al. 

Genetic and environmental risk assessment for 

colorectal cancer risk in primary care practice 

settings: a pilot study. Genet Med 2007;9(6):378-

84. Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

567. Nam RK, Toi A, Klotz LH, et al. Nomogram 

prediction for prostate cancer and aggressive 

prostate cancer at time of biopsy: utilizing all risk 

factors and tumor markers for prostate cancer. 

Can J Urol 2006;13 Suppl 2:2-10. PM:16672122 

Excluded: Not an eligible study design, 

568. Nanda R, Schumm LP, Cummings S, et al. 

Genetic testing in an ethnically diverse cohort of 

high-risk women: a comparative analysis of 

BRCA1 and BRCA2 mutations in American 

families of European and African ancestry. 

JAMA 2005;294(15):1925-33. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

569. Narod SA, Offit K. Prevention and management 

of hereditary breast cancer. J Clin Oncol 

2005;23(8):1656-63. 

Excluded: Not an eligible study design, OVIDEmbase. 

D-29
570. Negri E, Decarli A, La Vecchia C, et al. 

Identification of high risk groups for breast 

cancer by means of logistic models. J Clin 

Epidemiol 1990;43(5):413-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

571. Neilson AR, Whynes DK. Determinants of 

persistent compliance with screening for 

colorectal cancer. Soc Sci Med 1995;41(3):365-

74. Excluded: Not an eligible study design, 

OVID-Embase. 

572. Neise C, Rauchfuss M, Paepke S, et al. Risk 

perception and psychological strain in women 

with a family history of breast cancer. Onkologie 

2001;24(5):470-5. Excluded: Not an eligible 

study design, OVID-Medline. 

573. Nelson HD, Huffman LH, Fu R, et al. Genetic 

risk assessment and BRCA mutation testing for 

breast and ovarian cancer susceptibility: 

Systematic evidence review for the U.S. 

Preventive Services Task Force. Ann Intern Med 

2005;143(5):362-47. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

574. Ng KK, Fung SY, Chow LW. Practice of breast 

self-examination among high risk Chinese 

women in Hong Kong. Chin Med J (Engl) 

2000;113(12):1100-3. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

575. Ngo SN, Williams DB, Cobiac L, et al. Does 

garlic reduce risk of colorectal cancer? A 

systematic review. J Nutr 2007;137(10):2264-9. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

576. 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;10(Pt:1):1-16. 

Excluded: Not an eligible study design, OVIDMedline. 

577. Novotny J, Pecen L, Petruzelka L, et al. Breast 

cancer risk assessment in the Czech female 

population--an adjustment of the original Gail 

model. Breast Cancer Res Treat 2006;95(1):29-

35. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

578. Ohori M, Swindle P. Nomograms and 

instruments for the initial prostate evaluation: the 

ability to estimate the likelihood of identifying 

prostate cancer. Semin Urol Oncol 

2002;20(2):116-22. PM:12012297 

Excluded: Not an eligible study design 

579. Okasha M, McCarron P, Gunnell D, et al. 

Exposures in childhood, adolescence and early 

adulthood and breast cancer risk: a systematic 

review of the literature. [Review] [243 refs]. 

Breast Cancer Res Treat 2003;78(2):223-76. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

580. 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 first-degree relatives? 

Results from a randomized clinical trial. Breast J 

2007;13(1):19-27. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

581. Olsen CM, Green AC, Whiteman DC, et al. 

Obesity and the risk of epithelial ovarian cancer: 

a systematic review and meta-analysis. Eur J 

Cancer 2007;43(4):690-709. 

Excluded: Not an eligible population, OVIDMedline. 

582. Olsen CM, Bain CJ, Jordan SJ, et al. Recreational 

physical activity and epithelial ovarian cancer: A 

case-control study, systematic review, and metaanalysis. Cancer Epidemiol Biomarkers Prev 

2007;16(11):2321-30. 

Excluded: Not an eligible population, OVIDEmbase. 

583. Optenberg SA, Clark JY, Brawer MK, et al. 

Development of a decision-making tool to predict 

risk of prostate cancer: the Cancer of the Prostate 

Risk Index (CAPRI) test. Urology 

1997;50(5):665-72. PM:9372872 

Excluded: Not an eligible study design 

584. Ormondroyd E, Moynihan C, Watson M, et al. 

Disclosure of genetics research results after the 

death of the patient participant: a qualitative 

study of the impact on relatives. J Genet Couns 

2007;16(4):527-38. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

585. Otto SJ, Fracheboud J, Looman CW, et al. 

Initiation of population-based mammography 

screening in Dutch municipalities and effect on 

breast-cancer mortality: a systematic review. 

Lancet 2003;361(9367):1411-7. 

Excluded: Not an eligible population, OVIDMedline. 

586. Palmer RC, Emmons KM, Fletcher RH, et al. 

Familial risk and colorectal cancer screening 

health beliefs and attitudes in an insured 

population. Prev Med 2007;45(5):336-41. 

Excluded: Not an eligible study design, OVIDMedline. 

587. Palomares MR, Machia JR, Lehman CD, et al. 

Mammographic density correlation with Gail 

model breast cancer risk estimates and 

component risk factors. Cancer Epidemiol 

Biomarkers Prev 2006;15(7):1324-30. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

588. Papagrigoriadis S. Follow-up of patients with 

colorectal cancer: The evidence is in favour but 

we are still in need of a protocol. Int J Surg 

2007;5(2):120-8. Excluded: Not an eligible study 

design, OVID-Embase. 

D-30
589. Park JG, Vasen HF, Park YJ, et al. Suspected 

HNPCC and Amsterdam criteria II: evaluation of 

mutation detection rate, an international 

collaborative study. Int J Colorectal Dis 

2002;17(2):109-14. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

590. Park,N. Effects of breast cancer risk, 

psychological distress, and dispositional 

optimism on immune responses in healthy 

women Excluded: Not an eligible publication 

type, OVID-Cinahl. 

591. Parmigiani G, Chen S, Iversen ES, Jr., et al. 

Validity of models for predicting BRCA1 and 

BRCA2 mutations. Summary for patients in Ann 

Intern Med. 2007 Oct 2;147(7):I38; PMID: 

17909202. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

592. Pasini B, Casalis Cavalchini GC, Genovese T, et 

al. Evaluating breast cancer risk: available 

models to assess individual breast cancer risk and 

probability to be a BRCA mutation carrier. J Exp 

Clin Cancer Res 2002;21(Suppl. 3):23-9. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

593. Patenaude AF, Schneider KA, Kieffer SA, et al. 

Acceptance of invitations for p53 and BRCA1 

predisposition testing: Factors infleuencing 

potential utilization of cancer genetic testing 

cancer genetic testing. Psychooncology 

1996;5(3):241-50. 

Excluded: Not an eligible population, OVIDEmbase. 

594. Percesepe A, Anti M, Roncucci L, et al. The 

effect of family size on estimates of the 

frequency of hereditary non-polyposis colorectal 

cancer. Br J Cancer 1995;72(5):1320-3. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

595. Perkins JJ, Sanson-Fisher RW, Clarke SJ, et al. 

An exploration of screening practices for prostate 

cancer and the associated community 

expenditure. Br J Urol 1998;82(4):524-9. 

Excluded: Not an eligible study design, OVIDMedline. 

596. Perry N, Broeders M, de Wolf C, et al. European 

guidelines for quality assurance in breast cancer 

screening and diagnosis. Fourth edition--

summary document. Ann Oncol 2008;19(4):614-

22. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

597. Peshkin BN, Schwartz MD, Isaacs C, et al. 

Utilization of breast cancer screening in a 

clinically based sample of women after BRCA1/2 

testing. Cancer Epidemiol Biomarkers Prev 

2002;11(10:Pt 1):t-8 Excluded: Not an eligible 

population, OVID-Medline. 

598. Pestalozzi BC, Luporsi-Gely E, Jost LM, et al. 

ESMO Minimum Clinical Recommendations for 

diagnosis, adjuvant treatment and follow-up of 

primary breast cancer. Ann Oncol 

2005;16:Suppl-9 

Excluded: Family history not systematically 

collected, OVID-Medline. 

599. Peters NHGM, Borel R, I, Zuithoff NPA, et al. 

Meta-analysis of MR imaging in the diagnosis of 

breast lesions. Radiology 2008;246(1):116-24. 

Excluded: Not an eligible population, OVIDEmbase. 

600. Peterson SK, Watts BG, Koehly LM, et al. How 

families communicate about HNPCC genetic 

testing: findings from a qualitative study. Am J 

Med Genet 2003;Part(1):78-86. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

601. Petro-Nustas WI. Factors associated with 

mammography utilization among Jordanian 

women. J Transcult Nurs 2001;12(4):284-91. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

602. Phillips KA, Jenkins MA, Lindeman GJ, et al. 

Risk-reducing surgery, screening and 

chemoprevention practices of BRCA1 and 

BRCA2 mutation carriers: a prospective cohort 

study. Clin Genet 2006;70(3):198-206. 

Excluded: Not an eligible population, OVIDMedline. 

603. Phillips,M.A. Reliability of a statistical 

instrument for predicting BRCA1/BRCA2 

genetic mutation carrier status. 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

604. Pieterse K, van Dooren S, Seynaeve C, et al. 

Passive coping and psychological distress in 

women adhering to regular breast cancer 

surveillance. Psychooncology 2007;16(9):851-8. 

Excluded: Not an eligible study design, OVIDPsycInfo. 

605. Pinol V, Castells A, Andreu M, et al. Accuracy of 

revised Bethesda guidelines, microsatellite 

instability, and immunohistochemistry for the 

identification of patients with hereditary 

nonpolyposis colorectal cancer. JAMA 

2005;293(16):1986-94. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

606. Pittler MH, Ernst E. Clinical effectiveness of 

garlic (Allium sativum). Mol Nutr Food Res 

2007;51(11):1382-5. 

Excluded: Not an eligible study design, OVIDMedline. 

607. Podoloff DA, Advani RH, Allred C, et al. NCCN 

Task Force report: Positron Emission 

Tomography (PET)/Computed Tomography (CT) 

scanning in cancer. J Natl Compr Cancer Netw 

2007;5(SUPPL. 1):S 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

D-31
608. Polednak AP. Knowledge of colorectal cancer 

and use of screening tests among higher-risk 

persons. J Cancer Educ 1990;5(2):115-24. 

Excluded: Not an eligible population, OVIDEmbase. 

609. Polednak AP, Lane DS, Burg MA. Risk 

perception, family history, and use of breast 

cancer screening tests. Cancer Detect Prev 

1991;15(4):257-63. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

610. Potter CE, Beldock JG. Object Class Networks 

(OCNs) for interface-independent calculation 

with Gail and Claus models. Ann N Y Acad Sci 

1995;768:308-11. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

611. Price MA, Butow PN, Lo SK, et al. Predictors of 

cancer worry in unaffected women from high risk 

breast cancer families: risk perception is not the 

primary issue. J Genet Couns 2007;16(5):635-44. 

Excluded: Not an eligible study design, OVIDMedline. 

612. Purkayastha S, Tekkis PP, Athanasiou T, et al. 

Magnetic resonance colonography versus 

colonoscopy as a diagnostic investigation for 

colorectal cancer: a meta-analysis.[see comment]. 

Clin Radiol 2005;60(9):980-9. 

Excluded: Not an eligible population, OVIDMedline. 

613. Pylvanainen K, Kairaluoma M, Mecklin JP. 

Compliance and Satisfaction with Long-Term 

Surveillance in Finnish HNPCC Families. Fam 

Cancer 2006;5(2):175-8. 

Excluded: Not an eligible population, OVIDMedline. 

614. Qaseem A, Snow V, Sherif K, et al. Screening 

mammography for women 40 to 49 years of age: 

a clinical practice guideline from the American 

College of Physicians.[summary for patients in 

Ann Intern Med. 2007 Apr 3;146(7):I20; PMID: 

17404347]. Ann Intern Med 2007;146(7):511-5. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

615. Qin LQ, Xu JY, Wang PY, et al. Soyfood intake 

in the prevention of breast cancer risk in women: 

a meta-analysis of observational epidemiological 

studies. J Nutr Sci Vitaminol 2006;52(6):428-36. 

Excluded: Not an eligible population, OVIDMedline. 

616. Qin LQ, Xu JY, Wang PY, et al. Milk 

consumption is a risk factor for prostate cancer in 

Western countries: evidence from cohort studies. 

Asia Pac J Clin Nutr 2007;16(3):467-76. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

617. Qureshi N, Wilson B, Santaguida P, et al. 

Collection and use of cancer family history in 

primary care. Evid Rep Technol Assess No.159, 

AHRQ Publication No. 08-E001 (prepared by the 

McMaster University Evidence-based Practice 

Center under Contract No. 290-02-0020). 

Rockville, MD: Agency for Health Care 

Research and Quality; 2007 Oct. Available at: 

http://www.ahrq.gov/clinic/tp/famhisttp.htm

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

618. Rabeneck L, Rumble RB, Axler J, et al. Cancer 

Care Ontario Colonoscopy Standards: Standards 

and evidentiary base. Can J Gastroenterol 

2007;21(Suppl. D):5D-24D. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

619. Rabin C, Pinto B. Cancer-related beliefs and 

health behavior change among breast cancer 

survivors and their first-degree relatives. 

Psychooncology 2006;15(8):701-12. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

620. Radtke HB, Sebold CD, Allison C, et al. 

Neurofibromatosis type 1 in genetic counseling 

practice: Recommendations of the national 

society of genetic counselors. J Genet Couns 

2007;16(4):387-407. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

621. Rahman SM, Dignan MB, Shelton BJ. Factors 

influencing adherence to guidelines for screening 

mammography among women aged 40 years and 

older. Ethn Dis 2003;13(4):477-84. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

622. Rahman SMM, Dignan MB, Shelton BJ. A 

theory-based model for predicting adherence to 

guidelines for screening mammography among 

women age 40 and older. Int J Canc Prev 

2005;2(3):169-79. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

623. Rai T, Clements A, Bukach C, et al. What 

influences men's decision to have a prostatespecific antigen test? A qualitative study. Fam 

Pract 2007;24(4):365-71. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

624. Rakowski W, Breen N, Meissner H, et al. 

Prevalence and correlates of repeat 

mammography among women aged 55-79 in the 

Year 2000 National Health Interview Survey. 

Prev Med 2004;39(1):1-10. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

625. 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: Family history not systematically 

collected, OVID-Medline. 

D-32
626. Ramsoekh D, van Leerdam ME, Tops CM, et al. 

The use of genetic testing in hereditary colorectal 

cancer syndromes: genetic testing in HNPCC, 

(A)FAP and MAP. Clin Genet 2007;72(6):562-7. 

Excluded: Not an eligible population, OVIDMedline. 

627. Ray JA, Loescher LJ, Brewer M. Risk-reduction 

surgery decisions in high-risk women seen for 

genetic counseling. J Genet Couns 

2005;14(6):473-84. Excluded: Not an eligible 

study design, OVID-Medline. 

628. Rees G, Fry A, Cull A, et al. Illness perceptions 

and distress in women at increased risk of breast 

cancer. Psychol Health 2004;19(6):749-65. 

Excluded: Not an eligible study design, OVIDCinahl. 

629. Rees G, Gaff C, Young MA, et al. Health beliefs 

and behaviors of women who have received 

genetic counseling for breast cancer. J Genet 

Couns 2007;16(4):457-68. Excluded: Not an 

eligible population, OVID-Medline. 

630. Reichelt JG, Dahl AA, Heimdal K, et al. Uptake 

of genetic testing and pre-test levels of mental 

distress in Norwegian families with known 

BRCA1 mutations. Dis Markers 1999;15(1-

3):139-43. 

Excluded: Not an eligible study design, OVIDMedline. 

631. Rex DK, ACG Board of Trustees. American 

College of Gastroenterology action plan for 

colorectal cancer prevention. Am J Gastroenterol 

2004;99(4):574-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

632. Rex DK, Kahi CJ, Levin B, et al. Guidelines for 

Colonoscopy Surveillance after Cancer 

Resection: A Consensus Update by the American 

Cancer Society and US Multi-Society Task Force 

on Colorectal Cancer. CA Cancer J Clin 

2006;56(3):160-7. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

633. Reyes CM, Allen BA, Terdiman JP, et al. 

Comparison of selection strategies for genetic 

testing of patients with hereditary nonpolyposis 

colorectal carcinoma: effectiveness and costeffectiveness. Cancer 2002;95(9):1848-56. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

634. Richardson JL, Danley K, Mondrus GT, et al. 

Adherence to screening examinations for 

colorectal cancer after diagnosis in a first-degree 

relative. Prev Med 1995;24(2):166-70. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

635. Rieck GC, Lim K, Rogers MT, et al. Screening 

for familial ovarian cancer--management and 

outcome of women with moderate to high risk of 

developing ovarian cancer. Int J Gynecol Cancer 

2006;16(Suppl.1)86-91. 

Excluded: Not an eligible population, OVIDMedline. 

636. Rimer BK, Schildkraut JM, Lerman C, et al. 

Participation in a women's breast cancer risk 

counseling trial. Who participates? Who 

declines? High Risk Breast Cancer Consortium. 

Cancer 1996;77(11):2348-55. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

637. Rini C, Jandorf L, Valdimarsdottir H, et al. 

Distress among inflammatory bowel disease 

patients at high risk for colorectal cancer: a 

preliminary investigation of the effects of family 

history of cancer, disease duration, and perceived 

social support. sychooncology 2008;17(4):354-

62. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

638. Ritvo P, Robinson G, Irvine J, et al. A 

longitudinal study of psychological adjustment to 

familial genetic risk assessment for ovarian 

cancer. Gynecol Oncol 1999;74(3):331-7. 

Excluded: Not an eligible population, OVIDMedline. 

639. Ritvo P, Irvine J, Robinson G, et al. 

Psychological adjustment to familial-genetic risk 

assessment for ovarian cancer: predictors of 

nonadherence to surveillance recommendations. 

Gynecol Oncol 2002;84(1):72-80. 

Excluded: Not an eligible study design, OVIDMedline. 

640. Rockhill B, Byrne C, Rosner B, et al. Breast 

cancer risk prediction with a log-incidence 

model: evaluation of accuracy. J Clin Epidemiol 

2003;56(9):856-61. 

Excluded: Not an eligible study design, OVIDMedline. 

641. Roddam AW, Duffy MJ, Hamdy FC, et al. Use 

of prostate-specific antigen (PSA) isoforms for 

the detection of prostate cancer in men with a 

PSA level of 2-10 ng/ml: systematic review and 

meta-analysis. Eur Urol 398;48(3):386-99. 

Excluded: Not an eligible population, OVIDMedline. 

642. Rodriguez-Moranta F, Castells A, Andreu M, et 

al. Clinical performance of original and revised 

Bethesda guidelines for the identification of 

MSH2/MLH1 gene carriers in patients with 

newly diagnosed colorectal cancer: proposal of a 

new and simpler set of recommendations. Am J 

Gastroenterol 2006;101(5):1104-11. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

643. 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: Family history not systematically 

collected, OVID-Medline. 

D-33
644. Roetzheim R, Fox SA, Leake B, et al. The 

influence of risk factors on breast carcinoma 

screening of Medicare-insured older women. 

National Cancer Institute Breast Cancer 

Screening Consortium. Cancer 

1996;78(12):2526-34. 

Excluded: Family history not systematically 

collected, VID-Medline. 

645. Roetzheim RG, Fox SA, Leake B. The effect of 

risk on changes in breast cancer screening rates in 

Los Angeles, 1988-1990. Cancer 

1994;74(2):625-31. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

646. Rojas, MP, Telaro, et al. Follow-up strategies for 

women treated for early breast cancer. Cochrane 

Database of Syst Rev 2008;(1): 

Excluded: Not an eligible intervention or 

outcome, OVID-Cochrane. 

647. Rojas MP, Telaro E, Russo A, et al. Follow-up 

strategies for women treated for early breast 

cancer. Cochrane Database Syst Rev 

2005;(1):CD001768 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

648. Ronco AL. Use of artificial neural networks in 

modeling associations of discriminant factors: 

Towards an intelligent selective breast cancer 

screening. Artif Intell Med 1999;16(3):299-309. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

649. Ropka ME, Wenzel J, Phillips EK, et al. Uptake 

rates for breast cancer genetic testing: a 

systematic review. Cancer Epidemiol Biomarkers 

Prev 2006;15(5):840-55. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

650. Rosen B, Kwon J, Fung Kee FM, et al. 

Systematic review of management options for 

women with a hereditary predisposition to 

ovarian cancer. Gynecol Oncol 2004;93(2):280-6. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

651. Rosman AS, Korsten MA. Meta-analysis 

comparing CT colonography, air contrast barium 

enema, and colonoscopy. Am J Med 

2007;120(3):203-10. 

Excluded: Not an eligible population, OVIDMedline. 

652. Rosolowich V, Breast Disease Committee of the 

Society of Obstetricians and Gynaecologists of 

Canada. Breast self-examination. J Obstet 

Gynaecol Can 2006;28(8):728-30. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

653. Rothemund Y, Paepke S, Flor H. Perception of 

risk, anxiety, and health behaviors in women at 

high risk for breast cancer. Int J Behav Med 

2001;8(3):230-9. 

Excluded: Not an eligible study design, OVIDEmbase. 

654. Rouleau I, Chiquette J, Plante M, et al. Changes 

in health-related behaviours following BRCA 1/2 

genetic testing: the case of hormone replacement 

therapy. J Obstet Gynaecol Can 

2004;26(12):1059-66. 

Excluded: Not an eligible population, OVIDMedline. 

655. 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 45(3):280-5. 

Excluded: Not an eligible study design, OVIDMedline. 

656. Rowse J, Brown K, Jandorf L, et al. Breast 

cancer specific distress prior to genetic 

counseling in women of African descent at 

increased risk of hereditary breast and ovarian 

cancer. J Genet Couns 2007;16(1):11 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

657. Royak-Schaler R, Klabunde CN, Greene WF, et 

al. Communicating breast cancer risk: patient 

perceptions of provider discussions. Medscape 

Womens Health 7(2):2-Apr 

Excluded: Not an eligible study design, OVIDMedline. 

658. Royak-Schaler R, DeVellis BM, Sorenson JR, et 

al. Breast cancer in African-American families. 

Risk perception, cancer worry, and screening 

practices of first-degree relatives. Ann N Y Acad 

Sci 1995;768:281-5. 

Excluded: Not an eligible study design, OVIDMedline. 

659. Ruthotto F, Papendorf F, Wegener G, et al. 

Participation in screening colonoscopy in firstdegree relatives from patients with colorectal 

cancer. Ann Oncol 2007;18(9):1518-22. 

Excluded: Not an eligible study design, OVIDMedline. 

660. Ryan EL. Risk perception, risk attribution, and 

risk modification beliefs among women with a 

family history of breast cancer Dissertation 

Abstract, 1998 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

661. Sabatino SA, Burns RB, Davis RB, et al. Breast 

carcinoma screening and risk perception among 

women at increased risk for breast carcinoma: 

results from a national survey. Cancer 

2004;100(11):2338-46. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

662. Saini SD, Kim HM, Schoenfeld P. Incidence of 

advanced adenomas at surveillance colonoscopy 

in patients with a personal history of colon 

adenomas: a meta-analysis and systematic 

review. Gastrointest Endosc 2006;64(4):614-26. 

Excluded: Not an eligible population, OVIDMedline. 

D-34
663. Salmon PG, Swank AM. Exercise-based disease 

management guidelines for individuals with 

cancer: Potential applications in a high-risk midsouthern state. Journal of Exercise Physiology 

Online 2002;5(4):1-10. 

Excluded: Not an eligible study design, OVIDEmbase. 

664. Salsman JM, Pavlik E, Boerner LM, et al. 

Clinical, demographic, and psychological 

characteristics of new, asymptomatic participants 

in a transvaginal ultrasound screening program 

for ovarian cancer. Prev Med 2004;39(2):315-22. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

665. Samad AKA, Taylor RS, Marshall T, et al. A 

meta-analysis of the association of physical 

activity with reduced risk of colorectal cancer. 

Colorectal Dis 2005;7(3):204-13. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

666. Sanjoaquin MA, Allen N, Couto E, et al. Folate 

intake and colorectal cancer risk: A metaanalytical approach. Int J Cancer 

2005;113(5):825-8. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

667. Saraiya M, Coughlin SS, Burke W, et al. The 

role of family history in personal prevention 

practices among US women physicians. 

Community Genetics 2001;4(2):102-8. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

668. Saslow D, Boetes C, Burke W, et al. American 

Cancer Society guidelines for breast screening 

with MRI as an adjunct to 

mammography.[erratum appears in CA Cancer J 

Clin. 2007 May-Jun;57(3):185]. CA Cancer J 

Clin 2007;57(2):75-89. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

669. Scardino P. Update: NCCN prostate cancer 

Clinical Practice Guidelines. J Natl Compr 

Cancer Netw 2005;3(Suppl.1):S29-S33. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

670. Scherr D, Swindle PW, Scardino PT. National 

Comprehensive Cancer Network guidelines for 

the management of prostate cancer. Urology 

2003;61(Suppl.2):14-24. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

671. Schildkraut JM, Lerman C, Lustbader E, et al. 

Adherence to mammography among subgroups 

of women at high risk for breast cancer. J 

Womens Health 1995;4(6):645-54. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

672. Schmidt S, Becher H, Chang-Claude J. Breast 

cancer risk assessment: use of complete pedigree 

information and the effect of misspecified ages at 

diagnosis of affected relatives. Hum Genet 

1998;102(3):348-56. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

673. Schnur JB, Valdimarsdottir HB, Montgomery 

GH, et al. Social constraints and distress among 

women at familial risk for breast cancer. Ann 

Behav Med 2004;28(2):142-8. 

Excluded: Not an eligible study design, OVIDMedline. 

674. Schnur JB, DiLorenzo TA, Montgomery GH, et 

al. Perceived risk and worry about prostate 

cancer: a proposed conceptual model. Behav Med 

2006;32(3):89-96. 

Excluded: Not an eligible study design, OVIDMedline. 

675. Schnur JB. Social constraints, avoidance, and 

psychological distress in women with and 

without family histories of breast cancer. 

Dissertation abstract. 2003 

Excluded: Not an eligible publication type, 

OVID-PsycInfo. 

676. Schreer I. Early detection and diagnosis of breast 

cancer. Breast Care 2006;1(4):227-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

677. Schwartz M, Lerman C, Daly M, et al. Utilization 

of ovarian cancer screening by women at 

increased risk. Cancer Epidemiol Biomarkers 

Prev 1995;4(3):269-73. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

678. Schwartz MD, Lerman C, Miller SM, et al. 

Coping disposition, perceived risk, and 

psychological distress among women at increased 

risk for ovarian cancer. Health Psychol 

1995;14(3):232-5. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

679. Schwartz MD, Taylor KL, Willard KS, et al. 

Distress, personality, and mammography 

utilization among women with a family history of 

breast cancer. Health Psychol 1999;18(4):327-32. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

680. Schwartz MD, Taylor KL, Willard KS. 

Prospective association between distress and 

mammography utilization among women with a 

family history of breast cancer. J Behav Med 

2003;26(2):105-17. 

Excluded: Not an eligible study design, OVIDMedline. 

681. Schwartz MD, Kaufman E, Peshkin BN, et al. 

Bilateral prophylactic oophorectomy and ovarian 

cancer screening following BRCA1/BRCA2 

mutation testing. J Clin Oncol 2003;21(21):4034-

41. 

Excluded: Not an eligible population, OVIDMedline. 

D-35
682. Seely D, Mills EJ, Wu P, et al. The effects of 

green tea consumption on incidence of breast 

cancer and recurrence of breast cancer: A 

systematic review and meta-analysis. Integr 

Cancer Ther 2005;4(2):144-55. Excluded: Not an 

eligible intervention or outcome, OVID-Embase. 

683. 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. Excluded: Family 

history not systematically collected, OVIDMedline. 

684. 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;16(4):526-34. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

685. Shaukat A, Scouras N, Schunemann HJ. Role of 

supplemental calcium in the recurrence of 

colorectal adenomas: a metaanalysis of 

randomized controlled trials. Am J Gastroenterol 

2005;100(2):390-4. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

686. 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: Family history not systematically 

collected, OVID-Medline. 

687. Shen Y, Yang Y, Inoue LY, et al. Role of 

detection method in predicting breast cancer 

survival: analysis of randomized screening 

trials.[see comment]. J Natl Cancer Inst 

2005;97(16):1195-203. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

688. Shergill AK, Terdiman JP. Refining Colorectal 

Cancer Screening Recommendations Based on 

Gender. Gastroenterology 2007;132(7):2605-6. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

689. Siddiqui AA, Patel A, Huerta S. Determinants of 

compliance with colonoscopy in patients with 

adenomatous colon polyps in a veteran 

population. Aliment Pharmacol Ther 2006;24(11-

12):1623-30. Excluded: Family history not 

systematically collected, OVID-Medline. 

690. Simard J, Dumont M, Moisan AM, et al. 

Evaluation of BRCA1 and BRCA2 mutation 

prevalence, risk prediction models and a 

multistep testing approach in French-Canadian 

families with high risk of breast and ovarian 

cancer.[erratum appears in J Med Genet. 2007 

Jul;44(7):471]. J Med Genet 2007;44(2):107-21. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

691. Sinicrope PS, Vernon SW, Diamond PM, et al. 

Development and preliminary validation of the 

cancer family impact scale for colorectal cancer. 

Genet Test 2008;12(1):161-9. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

692. Sivell S, Iredale R, Gray J, et al. Cancer genetic 

risk assessment for individuals at risk of familial 

breast cancer. [Review] [93 refs]. Cochrane 

Database Syst Rev 2007;(2):CD003721 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

693. 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: Family history not systematically 

collected, OVID-Medline. 

694. Smith RA, Saslow D, Sawyer KA, et al. 

American Cancer Society guidelines for breast 

cancer screening: update. CA Cancer J Clin 

2003;53(3):141-69. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

695. Smith RA, Standiford CJ, Saraiya M. Updates in 

colon, cervical, breast, and prostate cancer 

screening. Patient Care Nurse Pract 2005;7. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

696. Smith RA, Cokkinides V, Eyre HJ. American 

Cancer Society guidelines for the early detection 

of cancer. CA Cancer J Clin 2005;55(1):31-44. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

697. Smith RA, Cokkinides V, Eyre HJ. American 

Cancer Society guidelines for the early detection 

of cancer. CA Cancer J Clin 2006;56(1):11-25. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

698. Smith TJ, Khatcheressian J. Review: 

chemotherapy and hormonal therapy reduce 

recurrence and mortality at 15 years in early 

breast cancer. Evid Based Med 2005;10(6):169 

Excluded: Not an eligible study design, OVIDCinahl. 

699. Society of Gastroenterology Nurses and 

Associates I. SGNA Guideline: Performance of 

flexible sigmoidoscopy by registered nurses for 

the purpose of colorectal cancer screening. 

Gastroenterol Nurs 2003;26(6):261-3. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

700. Sohl SJ, Moyer A. Tailored interventions to 

promote mammography screening: a metaanalytic review. Prev Med 2007;45(4):252-61. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

701. Song JM, Kim CB, Chung HC, et al. Prostatespecific antigen, digital rectal examination and 

transrectal ultrasonography: a meta-analysis for 

this diagnostic triad of prostate cancer in 

symptomatic korean men. Yonsei Med J 

2005;46(3):414-24. 

Excluded: Not an eligible population, OVIDMedline. 

D-36
702. Sooriakumaran P, Langley SEM, Laing RW, et 

al. COX-2 inhibition: A possible role in the 

management of prostate cancer? J Chemother 

2007;19(1):21-32. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

703. Sorscher S, Levonian P. BCRA 1 testing 

guidelines for high-risk patients. J Clin Oncol 

1997;15(4):1711 

Excluded: Not an eligible study design, OVIDMedline. 

704. Sosna J, Morrin MM, Kruskal JB, et al. CT 

colonography of colorectal polyps: a 

metaanalysis. AJR Am J Roentgenol 

2003;(6):1593-8. 

Excluded: Not an eligible population, OVIDMedline. 

705. Sotiriou C, Desmedt C. Gene expression profiling 

in breast cancer. Ann Oncol 2006;17(SUPPL. 

10):259-62. 

Excluded: Not an eligible study design, OVIDEmbase. 

706. Soyer MT, Ciceklioglu M, Ceber E. Breast 

cancer awareness and practice of breast self 

examination among primary health care nurses: 

influencing factors and effects of an in-service 

education. J Clin Nurs 2007;16(4):707-15. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

707. Spencer BA, Babey SH, Etzioni DA, et al. A 

population-based survey of prostate-specific 

antigen testing among California men at higher 

risk for prostate carcinoma. Cancer 

2006;106(4):765-74. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

708. Stamler LL. Review: limited evidence on regular 

breast examination does not support its 

effectiveness for reducing breast cancer deaths. 

Evid Based Nurs 2004;7(1):15 

Excluded: Not an eligible study design, OVIDCinahl. 

709. Standard TF, American Society of Colon and 

Rectal Surgeons, Collaborative Group of the 

Americas on Inherited Colorectal Cancer. 

Practice parameters for the identification and 

testing of patients at risk for dominantly inherited 

colorectal cancer. Dis Colon Rectum 

2001;44(10):1403 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

710. Stefanek ME, Wilcox P. First degree relatives of 

breast cancer patients: screening practices and 

provision of risk information. Cancer Detect 

Prev 1991;15(5):379-84. 

Excluded: Not an eligible study design, OVIDMedline. 

711. Stefanek ME, Helzlsouer KJ, Wilcox PM, et al. 

Predictors of and satisfaction with bilateral 

prophylactic mastectomy. Prev Med 

1995;24(4):412-9. 

Excluded: Not an eligible study design, OVIDMedline. 

712. Stephens JH, Moore JW. Can targeted 

intervention in CRC patients' relatives influence 

screening behaviour? A pilot study. Colorectal 

Dis 2008;10(2):179-86. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

713. Stoffel EM, Garber JE, Grover S, et al. Cancer 

surveillance is often inadequate in people at high 

risk for colorectal cancer. J Med Genet 

2003;40(5):e54 

Excluded: Not an eligible population, OVIDMedline. 

714. Stormorken AT, Muller W, Lemkemeyer B, et al. 

Prediction of the outcome of genetic testing in 

HNPCC kindreds using the revised Amsterdam 

criteria and immunohistochemistry. Familial 

Cancer 2001;1(3-4):169-73. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

715. Straus WL, Mansley EC, Gold KF, et al. 

Colorectal cancer screening attitudes and 

practices in the general population: a riskadjusted survey. J Public Health Manag Pract 

2005;11(3):244-51. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

716. Strzelczyk JJ, Dignan MB. Disparities in 

adherence to recommended followup on 

screening mammography: interaction of 

sociodemographic factors. Ethn Dis 

2002;12(1):77-86. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

717. Su X, Ma GX, Seals B, et al. Breast cancer early 

detection among Chinese women in the 

Philadelphia area. J Womens Health (Larchmt) 

2006;15(5):507-19. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

718. Sun C-L, Yuan J-M, Koh W-P, et al. Green tea, 

black tea and breast cancer risk: A meta-analysis 

of epidemiological studies. Carcinogenesis 

2006;27(7):1310-5. 

Excluded: Not an eligible population, OVIDEmbase. 

719. Sweetman J, Watson M, Norman A, et al. 

Feasibility of familial PSA screening: 

psychosocial issues and screening adherence. Br 

J Cancer 2006;94(4):507-12. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

D-37
720. Syngal S, Fox EA, Eng C, et al. Sensitivity and 

specificity of clinical criteria for hereditary nonpolyposis colorectal cancer associated mutations 

in MSH2 and MLH1. J Med Genet 

2000;37(9):641-5. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

721. Takakuwa KM, Ernst AA, Weiss SJ, et al. Breast 

cancer knowledge and preventive behaviors: An 

urban emergency department-based survey. 

Acad Emerg Med 2000;7(12):1393-8. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

722. Taplin SH, Thompson RS, Schnitzer F, et al. 

Revisions in the risk-based Breast Cancer 

Screening Program at Group Health Cooperative. 

Cancer 1990;66(4):812-8. PM:2386908 

Excluded: Not an eligible study design 

723. Tatemichi S, Miedema B, Leighton S. Breast 

cancer screening. First Nations communities in 

New Brunswick. Can Fam Physician 

2002;48:1084-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

724. Tavani A, Vecchia CL. Coffee, decaffeinated 

coffee, tea and cancer of the colon and rectum: A 

review of epidemiological studies, 1990-2003. 

Cancer Causes Control 2004;15(8):743-57. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

725. Taylor P, Potts HWW. Computer aids and human 

second reading as interventions in screening 

mammography: Two systematic reviews to 

compare effects on cancer detection and recall 

rate. Eur J Cancer 2008;44(6):798-807. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

726. Taylor R, Ivanov O, Page A, et al. Predictors of 

non-attendance from BreastScreen NSW in 

women who report current mammography 

screening. Aust N Z J Public Health 

2003;27(6):581-7. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

727. Taylor R, Taguchi K. Tamoxifen for breast 

cancer chemoprevention: low uptake by high-risk 

women after evaluation of a breast lump. Ann 

Fam Med 2005;3(3):242-7. 

Excluded: Not an eligible study design, OVIDMedline. 

728. Taylor SA, Laghi A, Lefere P, et al. European 

society of gastrointestinal and abdominal 

radiology (ESGAR): Consensus statement on CT 

colonography. Eur Radiol 2007;17(2):575-9. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

729. Tchou J, Hou N, Rademaker A, et al. Acceptance 

of tamoxifen chemoprevention by physicians and 

women at risk. Cancer 2004;100(9):1800-6. 

Excluded: Not an eligible study design, OVIDMedline. 

730. Teillac P. The global state of prostate cancer: 

New diagnostic tools, minimal requirements for 

diagnosis and staging, and guidelines in the 

second millennium. BJU Int 2004;94(Suppl 3):3-

4. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

731. Thiel LM. Health beliefs and breast cancer 

screening behaviors of women religious in 

America. Doctoral dissertation, research. 

Excluded: Not an eligible publication type, 

OVID-Cinahl. 

732. Thirlaway K, Fallowfield L, Nunnerley H, et al. 

Anxiety in women "at risk' of developing breast 

cancer. Br J Cancer 1996;73(11):1422-4. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

733. Thompson IM, Ankerst DP, Chi C, et al. 

Assessing prostate cancer risk: Results from the 

Prostate Cancer Prevention Trial. J Natl Cancer 

Inst 2006;98(8):529-34. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

734. Thomssen C. AGO recommendations for the 

diagnosis and therapy of breast cancer. Breast 

Care 2007;2(4):244-50. 

Excluded: Not an eligible intervention or 

outcome, OVID-Cinahl. 

735. Thorogood M, Simera I, Dowler E, et al. A 

systematic review of population and community 

dietary interventions to prevent cancer. Nutr Res 

Rev 2007;20(1):74-88. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

736. Thrasher JF, Cummings KM, Michalek AM, et 

al. Colorectal cancer screening among individuals 

with and without a family history. J Public Health 

Manag Pract 2002;8(2):1-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

737. Tice JA, Cummings SR, Ziv E, et al. 

Mammographic breast density and the Gail 

model for breast cancer risk prediction in a 

screening population. Breast Cancer Res Treat 

2005;94(2):115-22. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

738. Tice JA, Miike R, Adduci K, et al. Nipple 

aspirate fluid cytology and the Gail model for 

breast cancer risk assessment in a screening 

population. Cancer Epidemiol Biomarkers Prev 

2005;14(2):324-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

739. Tice JA, Cummings SR, Smith-Bindman R, et al. 

Using clinical factors and mammographic breast 

density to estimate breast cancer risk: 

development and validation of a new predictive 

model. Ann Intern Med 2008;148(5):337-47. 

PM:18316752 

Excluded: Not an eligible study design. 

D-38
740. Tiller K, Meiser B, Butow P, et al. Psychological 

impact of prophylactic oophorectomy in women 

at increased risk of developing ovarian cancer: a 

prospective study. Gynecol Oncol 

2002;86(2):212-9. 

Excluded: Not an eligible study design, OVIDMedline. 

741. Tinley ST, Houfek J, Watson P, et al. Screening 

adherence in BRCA1/2 families is associated 

with primary physicians' behavior. Am J Med 

Genet 2004;Part(1):5-11. 

Excluded: Not an eligible population, OVIDMedline. 

742. Touvier M, Kesse E, Volatier JL, et al. Dietary 

and cancer-related behaviors of vitamin/mineral 

dietary supplement users in a large cohort of 

French women. Eur J Nutr 2006;45(4):205-14. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

743. Trafalis DTP, Athanassiou AE. A guideline for 

the management of women at substantially 

increased risk of breast cancer development. J B 

U ON 2005;10(4):443-58. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

744. Trask PC, Paterson AG, Wang C, et al. Cancerspecific worry interference in women attending a 

breast and ovarian cancer risk evaluation 

program: impact on emotional distress and health 

functioning. Psychooncology 2001;10(5):349-60. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

745. Trepanier A, Ahrens M, McKinnon W, et al. 

Genetic cancer risk assessment and counseling: 

recommendations of the national society of 

genetic counselors. J Genet Couns 

2004;13(2):83-114. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

746. Trock BJ, Hilakivi-Clarke L, Clarke R. Metaanalysis of soy intake and breast cancer risk.[see 

comment]. J Natl Cancer Inst 2006;98(7):459-71. 

Excluded: Not an eligible population, OVIDMedline. 

747. Tsouskas LI, Liaros A, Tzitzikas J, et al. The use 

of an expert system of composite risk factors in 

breast cancer screening. Stud Health Technol 

Inform 1997;43:t-63 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

748. Tsouskas LI, Noula M, Dimopoulos P. Practicing 

an expert system for definition of high-risk group 

in breast cancer screening. ICUS Nurs Web J 

2005;(22):5p 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

749. Turner-Cobb JM, Bloor LE, Whittemore AS, et 

al. Disengagement and social support moderate 

distress among women with a family history of 

breast cancer. Breast J 2006;12(1):7-15. 

Excluded: Not an eligible study design, OVIDMedline. 

750. Tyler CV, Jr., Snyder CW. Cancer risk 

assessment: examining the family physician's 

role. J Am Board Fam Med 2006;19(5):468-77. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

751. Tyrer J, Duffy SW, Cuzick J. A breast cancer 

prediction model incorporating familial and 

personal risk factors.[erratum appears in Stat 

Med. 2005 Jan 15;24(1):156]. Stat Med 

2004;23(7):1111-30. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

752. U.S.Preventive Services Task Force. Screening 

for prostate cancer: recommendations and 

rationale. Am Fam Physician 2003;67(4):787-92. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

753. U.S.Preventive Services Task Force. Routine 

Vitamin Supplementation to Prevent Cancer and 

Cardiovascular Disease: Recommendations and 

Rationale. Ann Intern Med 2003;139(1):51-5. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

754. U.S.Preventive Services Task Force. Clinical 

guidelines. Genetic risk assessment and BRCA 

mutation testing for breast and ovarian cancer 

susceptibility: recommendation statement 

[corrected] [published erratum appears in Ann 

Intern Med 2005;143(7):547]. Ann Intern Med 

2005;143(5):355-61. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

755. U.S.Preventive Services Task Force. Summaries 

for patients. Genetic risk assessment and BRCA 

mutation testing for breast and ovarian cancer 

susceptibility: U.S. Preventive Services Task 

Force recommendations.[see comment]. Ann 

Intern Med 2005;143(5):I47 

Excluded: Not an eligible study design, OVIDMedline. 

756. U.S.Preventive Services Task Force. Genetic risk 

assessment and BRCA mutation testing for breast 

and ovarian cancer susceptibility: 

recommendation statement.[erratum appears in 

Ann Intern Med. 2005 Oct 4;143(7):547]. Ann 

Intern Med 2005;143(5):355-61. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

757. U.S.Preventive Services Task Force. Screening 

for ovarian cancer: recommendation statement. 

U.S. Preventive Services Task Force. Am Fam 

Physician 2005;71(4):759-62. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

758. U.S.Preventive Services Task Force. Routine 

aspirin or nonsteroidal anti-inflammatory drugs 

for the primary prevention of colorectal cancer: 

recommendation statement. Am Fam Physician 

2007;76(1):109-13. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

D-39
759. Uyei A, Peterson SK, Erlichman J, et al. 

Association between clinical characteristics and 

risk-reduction interventions in women who 

underwent BRCA1 and BRCA2 testing: a singleinstitution study. Cancer 2006;107(12):2745-51. 

Excluded: Not an eligible population, OVIDMedline. 

760. 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;93(7):955-60. 

Excluded: Not an eligible study design, OVIDMedline. 

761. Vadaparampil ST, Jacobsen PB, Kash K, et al. 

Factors predicting prostate specific antigen 

testing among first-degree relatives of prostate 

cancer patients. Cancer Epidemiol Biomarkers 

Prev 2004;13(5):753-8. 

Excluded: Not an eligible study design, OVIDMedline. 

762. Vahteristo P, Eerola H, Tamminen A, et al. A 

probability model for predicting BRCA1 and 

BRCA2 mutations in breast and breast-ovarian 

cancer families. Br J Cancer 2001;84(5):704-8. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

763. Valdimarsdottir HB, Bovbjerg DH, Kash KM, et 

al. Psychological distress in women with a 

familial risk of breast cancer. Psychooncology 

1995;4(2):133-41. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

764. Valdimarsdottir HB, Bovbjerg DH, Brown K, et 

al. Cancer-specific distress is related to women's 

decisions to undergo BRCA1 testing. Cancer 

Research Therapy and Control 1999;8(1-2):61-8. 

Excluded: Not an eligible publication type, 

OVID-Embase. 

765. Valdimarsdottir HB, Zakowski SG, Gerin W, et 

al. Heightened psychobiological reactivity to 

laboratory stressors in healthy women at familial 

risk for breast cancer. J Behav Med 

2002;25(1):51-65. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

766. van Asperen CJ, Jonker MA, Jacobi CE, et al. 

Risk estimation for healthy women from breast 

cancer families: new insights and new strategies. 

Cancer Epidemiol Biomarkers Prev 

2004;13(1):87-93. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

767. Van Cutsem EJ, Oliveira J, Kataja VV, et al. 

ESMO Minimum Clinical Recommendations for 

diagnosis, treatment and follow-up of advanced 

colorectal cancer. Ann Oncol 2005;16:Suppl-9 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

768. Van Cutsem EJD, Kataja VV. ESMO minimum 

clinical recommendations for diagnosis, adjuvant 

treatment and follow-up of colon cancer. Ann 

Oncol 2005;16(Suppl. 1):i16-i17 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

769. van der Rhee HJ, de Vries E, Coebergh JWW. 

Does sunlight prevent cancer? A systematic 

review. Eur J Cancer 2006;42(14):2222-32. 

Excluded: Not an eligible population, OVIDEmbase. 

770. Van Der KT, Lopes C, Santonja C, et al. 

Guidelines for processing and reporting of 

prostatic needle biopsies. J Clin Pathol 

2003;56(5):336-40. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

771. van Dooren S, Rijnsburger AJ, Seynaeve C, et al. 

Psychological distress and breast selfexamination frequency in women at increased 

risk for hereditary or familial breast cancer. 

Community Genet 2003;6(4):235-41. 

Excluded: Not an eligible study design, OVIDMedline. 

772. van Dooren S, Rijnsburger AJ, Seynaeve C, et al. 

Psychological distress in women at increased risk 

for breast cancer: the role of risk perception. Eur 

J Cancer 2004;40(14):2056-63. 

Excluded: Not an eligible population, OVIDMedline. 

773. 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;89(1):75-80. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

774. van Dooren S, Seynaeve C, Rijnsburger AJ, et al. 

Exploring the course of psychological distress 

around two successive control visits in women at 

hereditary risk of breast cancer. Eur J Cancer 

2005;41(10):1416-25. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

775. van Oostrom I, Meijers-Heijboer H, 

Duivenvoorden HJ, et al. Comparison of 

individuals opting for BRCA1/2 or HNPCC 

genetic susceptibility testing with regard to 

coping, illness perceptions, illness experiences, 

family system characteristics and hereditary 

cancer distress. Patient Educ Couns 

2007;65(1):58-68. 

Excluded: Not an eligible population, OVIDMedline. 

776. Varghese SS, Wilson DB, Penberthy LT, et al. 

North American perspectives. Examining the 

evidence for breast self examination 

recommendations. Clin Governance Int J 

2006;11(3):225-33. 

Excluded: Not an eligible study design, OVIDCinahl. 

D-40
777. Vasen HF, Moslein G, Alonso A, et al. 

Guidelines for the clinical management of 

familial adenomatous polyposis (FAP). Gut 

2008;57(5):704-13. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

778. Vasey PA, Herrstedt J, Jelic S, et al. ESMO 

Minimum Clinical Recommendations for 

diagnosis, treatment and follow-up of epithelial 

ovarian carcinoma. Ann Oncol 2005;16(Suppl 

1):i13-5. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

779. Velayos FS, Terdiman JP, Walsh JM. Effect of 5-

aminosalicylate use on colorectal cancer and 

dysplasia risk: a systematic review and 

metaanalysis of observational studies. Am J 

Gastroenterol 2005;100(6):1345-53. 

Excluded: Not an eligible population, OVIDMedline. 

780. Velayos FS, Allen BA, Conrad PG, et al. Low 

rate of microsatellite instability in young patients 

with adenomas: reassessing the Bethesda 

guidelines. Am J Gastroenterol 

2005;100(5):1143-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

781. Veschi S, Aceto G, Scioletti AP, et al. High 

prevalence of BRCA1 deletions in BRCAPROpositive patients with high carrier probability. 

Ann Oncol 2007;18:Suppl-92 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

782. Vicini FA, Vargas C, Abner A, et al. Limitations 

in the use of serum prostate specific antigen 

levels to monitor patients after treatment for 

prostate cancer. J Urol 2005;173(5):1456-62. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

783. Vogel KJ, Atchley DP, Erlichman J, et al. 

BRCA1 and BRCA2 genetic testing in Hispanic 

patients: mutation prevalence and evaluation of 

the BRCAPRO risk assessment model. J Clin 

Oncol 2007;25(29):4635-41. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

784. Vogel VG, Graves DS, Vernon SW, et al. 

Mammographic screening of women with 

increased risk of breast cancer. Cancer 

1990;66(7):1613-20. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

785. Vogel VG. Can statin therapy reduce the risk of 

breast cancer? J Clin Oncol 2005;23(34):8553-5. 

Excluded: Not an eligible study design, OVIDEmbase. 

786. Vogel VG. Recent results from clinical trials 

using SERMs to reduce the risk of breast cancer. 

Ann N Y Acad Sci 2006;1089:127-42. 

Excluded: Not an eligible study design, OVIDMedline. 

787. Vogel VG. Chemoprevention in breast cancer. 

Cancer and Chemotherapy Reviews 

2007;2(1):33-40. 

Excluded: Not an eligible study design, OVIDEmbase. 

788. Von Roon AC, Karamountzos L, Purkayastha S, 

et al. Diagnostic precision of fecal calprotectin 

for inflammatory bowel disease and colorectal 

malignancy. Am J Gastroenterol 

2007;102(4):803-13. 

Excluded: Not an eligible study design, OVIDEmbase. 

789. Wade WM. Women receiving genetic counseling 

for breast cancer risk: Cancer worry, 

psychological distress, and risk recall accuracy. 

Dissertation Abstracts International: Section B: 

the Sciences and Engineering 2001;61(7-b):2865 

Excluded: Not an eligible publication type, 

OVID-Cochrane. 

790. Wagner A, van Kessel I, Kriege MG, et al. Long 

term follow-up of HNPCC gene mutation 

carriers: compliance with screening and 

satisfaction with counseling and screening 

procedures. Fam Cancer 2005;4(4):295-300. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

791. Wahlberg SS, Schmeits J, Thomas G, et al. 

Evaluation of microsatellite instability and 

immunohistochemistry for the prediction of 

germ-line MSH2 and MLH1 mutations in 

hereditary nonpolyposis colon cancer families. 

Cancer Res 2002;62(12):3485-92. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

792. Wainberg S, Husted J. Utilization of screening 

and preventive surgery among unaffected carriers 

of a BRCA1 or BRCA2 gene mutation. [Review] 

[27 refs]. Cancer Epidemiol Biomarkers Prev 

2004;13(12):1989-95. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

793. Walleser S, Griffiths A, Lord SJ, et al. What is 

the value of computered tomography 

colonography in patients screening positive for 

fecal occult blood? A systematic review and 

economic evaluation. [Review] [42 refs]. Clin 

Gastroenterol Hepatol 1368;5(12):1439-46. 

Excluded: Not an eligible population, OVIDMedline. 

794. Wallis M, Tarvidon A, Helbich T, et al. 

Guidelines from the European Society of Breast 

Imaging for diagnostic interventional breast 

procedures. Eur Radiol 2007;17(2):581-8. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

795. Walsh JME, Posner SF, Perez-Stable EJ. Colon 

cancer screening in the ambulatory setting. Prev 

Med 2002;35(3):209-18. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

D-41
796. Wampler NS, Saba L, Rahman SM, et al. Factors 

associated with adherence to recommendations 

for screening mammography among American 

Indian women in Colorado. Ethn Dis 

2006;16(4):808-14. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

797. Wane D, Lengacher CA. Integrative review of 

lycopene and breast cancer. Oncol Nurs Forum 

2006;33(1):127-37. 

Excluded: Not an eligible population, OVIDCinahl. 

798. Wang P-H, Chao H-T. A reconsideration of 

tamoxifen use for breast cancer. Taiwan J Obstet 

Gynecol 2007;46(2):93-5. 

Excluded: Not an eligible study design, OVIDEmbase. 

799. Wang Y, Sun G, Pan JG, et al. Performance of 

tPSA and f/tPSA for prostate cancer in Chinese. 

A systematic review and meta-analysis. Prostate 

Cancer Prostatic Dis 2006;9(4):374-8. 

Excluded: Not an eligible population, OVIDMedline. 

800. Wang Y-P, Pan T, Yang J-L, et al. Nonsteroidal 

anti-inflammatory drugs for prevention of 

colorectal neoplasms: A systematic review. 

Chinese Journal of Evidence-Based Medicine 

2005;5(6):438-43. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase 

801. Wardle J. Women at risk of ovarian cancer. J 

Natl Cancer Inst 1995;Monographs.(17):81-5. 

Excluded: Not an eligible publication type, 

OVID-Medline. 

802. Warner E. Intensive radiologic surveillance: A 

focus on the psychological issues. Ann Oncol 

2004;15(SUPPL. 1):i43-i47 

Excluded: Family history not systematically 

collected, OVID-Embase. 

803. Warner E, Messersmith H, Causer P, et al. 

Systematic review: using magnetic resonance 

imaging to screen women at high risk for breast 

cancer. [Review] [35 refs]. Ann Intern Med 

2008;148(9):671-9. 

Excluded: Not an eligible population, OVIDMedline. 

804. Wasvary HJ. Pathology features in Bethesda 

guidelines predict colorectal cancer microsatellite 

instability: A population-based study. Dis Colon 

Rectum 2007;50(10):1732-3. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

805. Watine JC, Bunting PS. Mass colorectal cancer 

screening: Methodological quality of practice 

guidelines is not related to their content validity. 

Clin Biochem 2008;41(7-8):459-66. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

806. Watson, M., Kash, K. M., Homewood, J., Ebbs, 

S., Murday, V., and Eeles, R., Does genetic 

counseling have any impact on management of 

breast cancer risk?, Genetic Testing, 9(2), 2005, 

p.167 – 174. 

Excluded: Not an eligible population, OVIDEmbase. 

807. Weik JL, Lum SS, Esquivel PA, et al. The Gail 

model predicts breast cancer in women with 

suspicious radiographic lesions. Am J Surg 

2005;190(4):526-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

808. Weinberg AD, Cooper HP, Lane M, et al. 

Screening behaviors and long-term compliance 

with mammography guidelines in a breast cancer 

screening program. Am J Prev Med 

1997;13(1):29-35. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

809. Weinberg DS. In the clinic.Colorectal cancer 

screening. Ann Intern Med 2008;148(3):ITC2-1-

16. 

Excluded: Model does not categorize risk or 

validate, OVID-Cinahl. 

810. Weinrich SP. Prostate cancer screening in highrisk men: African American Hereditary Prostate 

Cancer Study Network. Cancer 2006;106(4):796-

803. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

811. Weischer M, Bojesen SE, Ellervik C, et al. 

CHEK2*1100delC genotyping for clinical 

assessment of breast cancer risk: meta-analyses 

of 26,000 patient cases and 27,000 controls.[see 

comment]. [Review] [51 refs]. J Clin Oncol 

2008;26(4):542-8. 

Excluded: Not an eligible population, OVIDMedline. 

812. Weitzel JN, Lagos VI, Cullinane CA, et al. 

Limited family structure and BRCA gene 

mutation status in single cases of breast 

cancer.[see comment]. JAMA 

2007;297(23):2587-95. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

813. Weller DP, Owen N, Hiller JE, et al. Colorectal 

cancer and its prevention: prevalence of beliefs, 

attitudes, intentions and behaviour. Aust J Public 

Health 1995;19(1):19-23. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

814. Wellisch DK, Lindberg NM. A psychological 

profile of depressed and nondepressed women at 

high risk for breast cancer. Psychosomatics 

2001;42(4):330-6. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

D-42
815. 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. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

816. Wiernikowski J, Mohide EA. Review: adequately 

randomised trials showed that mammography 

screening did not significantly reduce breast 

cancer, cancer, or all cause mortality but 

increased breast surgeries. Evid Based Nurs 

2007;10(3):80 

Excluded: Not an eligible study design, OVIDCinahl. 

817. Williams GL, Clarke P, Vellacott KD. Anxieties 

should not be forgotten when screening relatives 

of colorectal cancer patients by colonoscopy. 

Colorectal Dis 2006;8(9):781-4. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

818. Winawer S, Fletcher R, Rex D, et al. Colorectal 

cancer screening and surveillance: clinical 

guidelines and rationale-Update based on new 

evidence. Gastroenterology 2003;124(2):544-60. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

819. Winawer SJ, Zauber AG, Fletcher RH, et al. 

Guidelines for colonoscopy surveillance after 

polypectomy: a consensus update by the US 

Multi-Society Task Force on Colorectal Cancer 

and the American Cancer Society. CA Cancer J 

Clin 184;56(3):143-59. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

820. Winawer SJ. New post-polypectomy surveillance 

guidelines. Practical Gastroenterology 

2007;31(8):30-42. 

Excluded: Model does not categorize risk or 

validate, OVID-Embase. 

821. Wolf B, Gruber S, Henglmueller S, et al. 

Efficiency of the revised Bethesda guidelines 

(2003) for the detection of mutations in mismatch 

repair genes in Austrian HNPCC patients. Int J 

Cancer 2006;118(6):1465-70. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

822. Wu TY, Guthrie BJ, Bancroft JM. An integrative 

review on breast cancer screening practice and 

correlates among Chinese, Korean, Filipino, and 

Asian Indian American women.[erratum appears 

in Health Care Women Int. 2005 Oct;26(9):877. 

Health Care for Women Int 2005;26(3):225-46. 

Excluded: Not an eligible intervention or 

outcome, OVID-Medline. 

823. Wullenweber HP, Sutter C, Autschbach F, et al. 

Evaluation of Bethesda guidelines in relation to 

microsatellite instability. Dis Colon Rectum 

2001;44(9):1281-9. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

824. Yan L, Spitznagel EL. Meta-analysis of soy food 

and risk of prostate cancer in men. Int J Cancer 

2005;117(4):667-9. 

Excluded: Not an eligible intervention or 

outcome, OVID-Embase. 

825. Yang K, Allen B, Conrad P, et al. Awareness of 

gynecologic surveillance in women from 

hereditary non-polyposis colorectal cancer 

families. Fam Cancer 2006;5(4):405-9. 

Excluded: Not an eligible study design, OVIDMedline. 

826. Yasui Y, Newcomb PA, Trentham-Dietz A, et al. 

Familial relative risk estimates for use in 

epidemiologic analyses. Am J Epidemiol 

2006;164(7):697-705. 

Excluded: Model does not categorize risk or 

validate, OVID-Medline. 

827. Yin LY, Wai KL, Chuan TN, et al. Factors 

influencing women undertaking screening 

mammography in primary care in Singapore. 

Singapore Nurs J 2007;34(3):74-80. 

Excluded: Family history not systematically 

collected, OVID-Cinahl. 

828. Yokoe T, Takei H, Horiguchi J, et al. Family 

history in participants of breast cancer screening. 

Oncol Rep 1997;4(5):973-6. 

Excluded: Family history not systematically 

collected, OVID-Embase. 

829. Yossepowitch O, Eggener SE, Bianco FJ, Jr., et 

al. Radical prostatectomy for clinically localized, 

high risk prostate cancer: critical analysis of risk 

assessment methods. J Urol 499;178(2):493-9. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

830. Zakowski SG, Valdimarsdottir HB, Bovbjerg 

DH, et al. Predictors of intrusive thoughts and 

avoidance in women with family histories of 

breast cancer. Ann Behav Med 1997;19(4):362-9. 

Excluded: Family history not systematically 

collected, OVID-PsycInfo. 

831. Zakowski SG, Valdimarsdottir HB, Bovbjerg 

DH. Emotional expressivity and intrusive 

cognitions in women with family histories of 

breast cancer: Application of a cognitive 

processing model. Br J Health Psychol 

2001;6(2):151-65. 

Excluded: Family history not systematically 

collected, OVID-PsycInfo. 

832. Zaloudik J, Coufal O, Kocakova I, et al. 

Chemoprevention of colorectal carcinoma in 

high-risk patients. Acta Univ Palacki Olomuc Fac 

Med 2000;143:109 

Excluded: Family history not systematically 

collected, OVID-Medline. 

833. Zapka J, Fisher G, Lemon S, et al. Relationship 

and distress in relatives of breast cancer patients. 

Families, Systems and Health 2006;24(2):198-

212. Excluded: Family history not systematically 

collected, OVID-Embase. 

D-43
D-44

834. Zapka JG, Stoddard A, Maul L, et al. Interval 

adherence to mammography screening 

guidelines. Med Care 1991;29(8):697-707. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

835. Zapka JG, Hosmer D, Costanza ME, et al. 

Changes in mammography use: economic, need, 

and service factors. Am J Public Health 

1992;82(10):1345-51. 

Excluded: Family history not systematically 

collected, OVID-Medline. 

836. Zhou B, Yang L, Wang L, et al. The association 

of tea consumption with ovarian cancer risk: A 

metaanalysis. Am J Obstet Gynecol 

2007;197(6):594-6. 

Excluded: Not an eligible population, OVIDMedline. 

837. Zhou B, Sun Q, Cong R, et al. Hormone 

replacement therapy and ovarian cancer risk: A 

meta-analysis. Gynecol Oncol 2008;108:641-51. 

Excluded: Not an eligible population, OVIDEmbase. 

838. Zwick YC. Outlining a pan-European colon 

cancer screening programme. Z Gastroenterol 

2008;46(Suppl.1):S52-S53 

Excluded: Not an eligible publication type, 

OVID-Embase. 
Appendix E - Partners, 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 

Partners 

Robert German, Dr.P.H., M.P.H. 

Associate Director for Science, Division of Cancer Prevention and Control, 

Centers for Disease Control and Prevention 

Atlanta, GA 

Rodolfo Valdez, Ph.D., M.Sc. 

National Office of Public Health Genomics 

Centers for Disease Control and Prevention 

Atlanta, GA 

Members of the Technical Expert Panel 

Lisa Madlensky, Ph.D. 

Assistant Professor, Cancer Prevention & Control Program 

University of San Diego 

San Diego, CA 

Louise Acheson, M.D., M.S. 

Professor of Family Medicine and Oncology 

Associate Professor of Reproductive Biology 

Case Western Reserve University and University Hospitals Case Medical Center 

Euclid, OH 

 E-1
Peer Reviewers 

Louise Acheson, M.D., M.S. 

Professor of Family Medicine and Oncology 

Associate Professor of Reproductive Biology 

Case Western Reserve University and University Hospitals Case Medical Center 

Euclid, OH , U.S.A 

George Browman, M.D., M.Sc. 

Senior Scientist, BC Cancer Agency 

Chair of the Cancer Guidelines Action Group of the Canadian Partnership Against Cancer 

Victoria, BC, C.A. 

W.Greg Feero, M.D., Ph.D. 

Senior Advisor for Genomic Medicine 

National Human Genome Research Institute 

National Institutes of Health 

Bethesda, MD, U.S.A. 

Andrew Freedman, M.D., M.Sc. 

National Cancer Institute, Epidemiologist 

Bethesda, MD, U.S.A. 

Joy Larsen Haidle, M.S., C.G.C. 

Genetic Counselor 

Hubert H. Humphrey Cancer Center 

Robbinsdale, MN, U.S.A. 

Lisa Madlensky, Ph.D. 

Assistant Professor, Cancer Prevention & Control Program 

University of San Diego 

San Diego, CA. U.S.A. 

Phuong Mai, M.D. 

Staff Clinical, Clinical Genetics Branch 

Division of Cancer Epidemiology and Genetics 

National Cancer Institute, National Institutes of Health 

Rockville, MD, U.S.A. 

Harvey J.Murff, M.D., M.P.H. 

Vanderbilt Epidemiology Center 

Institute for Medicine and Public Health 

Nashville, TN, U.S.A. 

 E-2
 E-3

Suzanne O'Neill, Ph.D., C.G.C. 

Associate Director, Northwestern University Graduate Program in Genetic Counseling 

Assistant Professor, Northwestern University Feinberg School of Medicine 

Chicago, IL, U.S.A. 

Nancie Petrucelli, M.S., C.G.C. 

Senior Genetic Counselor/Coordinator 

Cancer Genetic Counseling Service 

Barbara Ann Karmanos Cancer Institute 

Detroit, MI, U.S.A.