bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Prevalence and Framing of Health Disparities in Local Print News: Implications for Multilevel Interventions to Address Cancer Inequalities
Authors: Nagler Rebekah H. , Bigman Cabral A. , Ramanadhan Shoba , Ramamurthi Divya , Viswanath K.
Published: April 2023

Abstract
Background: Americans remain under-informed about cancer and other health disparities and the social determinants of health (SDH). The news media may be contributing to this knowledge deficit, whether by discussing these issues narrowly or ignoring them altogether. Because local media are particularly important in influencing public opinion and support for public policies, this study examines the prevalence and framing of disparities/SDH in local mainstream and ethnic print news.

Methods: We conducted a multi-method content analysis of local mainstream (English language) and ethnic (Spanish language) print news in two lower income cities in New England with substantial racial/ethnic minority populations. After establishing intercoder reliability (κ = 0.63–0.88), coders reviewed the primary English and Spanish language newspaper in each city, identifying both disparities and non-disparities health stories published between February 2010 and January 2011.

Results: Local print news coverage of cancer and other health disparities was rare. Of 650 health stories published across four newspapers during the one-year study period, only 21 (3.2%) discussed disparities/SDH. Although some stories identified causes of and solutions for disparities, these were often framed in individual (e.g., poor dietary habits) rather than social contextual terms (e.g., lack of food availability/affordability). Cancer and other health stories routinely missed opportunities to discuss disparities/SDH.

Conclusion: Local mainstream and ethnic media may be ideal targets for multilevel interventions designed to address cancer and other health inequalities.

Impact: By increasing media attention to and framing of health disparities, we may observe important downstream effects on public opinion and support for structural solutions to disparities, particularly at the local level. Cancer Epidemiol Biomarkers Prev; 25(4); 603–12. ©2016 AACR.

See all articles in this CEBP Focus section, “Multilevel Approaches to Addressing Cancer Health Disparities.”
Data from A Multistage Genetic Association Study Identifies Breast Cancer Risk Loci at 10q25 and 16q24
Authors: Higginbotham Kathryn S. , Breyer Joan P. , McReynolds Kate M. , Bradley Kevin M. , Schuyler Peggy A. , Plummer W. Dale , Freudenthal Marcia E. , Trentham-Dietz Amy , Newcomb Polly A. , Parl Fritz F. , Sanders Melinda E. , Page David L. , Egan Kathleen M. , Dupont William D. , Smith Jeffrey R.
Published: April 2023

Abstract
Background: Heritable risk for breast cancer includes an increasing number of common, low effect risk variants. We conducted a multistage genetic association study in a series of independent epidemiologic breast cancer study populations to identify novel breast cancer risk variants.

Methods: We tested 1,162 SNPs of greatest nominal significance from stage I of the Cancer Genetic Markers of Susceptibility breast cancer study (CGEMS; 1,145 cases, 1,142 controls) for evidence of replicated association with breast cancer in the Nashville Breast Cohort (NBC; 599 cases, 1,161 controls), the Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls), and BioVU Breast Cancer Study (BioVU; 1,172 cases, 1,172 controls).

Results: Among these SNPs, a series of validated breast cancer risk variants yielded expected associations in the study populations. In addition, we observed two previously unreported loci that were significantly associated with breast cancer risk in the CGEMS, NBC, and CBCS study populations and had a consistent, although not statistically significant, risk effect in the BioVU study population. These were rs1626678 at 10q25.3 near ENO4 and KIAA1598 (meta-analysis age-adjusted OR = 1.13 [1.07–1.20], P = 5.6 × 10−5), and rs8046508 at 16q23.1 in the eighth intron of WWOX (meta-analysis age-adjusted OR = 1.20 [1.10–1.31], P = 3.5 × 10−5).

Conclusions: Our data supports the association of two novel loci, at 10q25.3 and 16q23.1, with risk of breast cancer.

Impact: The expanding compendium of known breast cancer genetic risk variants holds increasing power for clinical risk prediction models of breast cancer, improving upon the Gail model. Cancer Epidemiol Biomarkers Prev; 21(9); 1565–73. ©2012 AACR.
Data from Diagnostic Delay and Sociodemographic Predictors of Stage at Diagnosis and Mortality in Unilateral and Bilateral Retinoblastoma
Authors: Ramírez-Ortiz Marco A. , Ponce-Castañeda M. Veronica , Cabrera-Muñoz M. Lourdes , Medina-Sansón Aurora , Liu Xinhua , Orjuela Manuela A.
Published: April 2023

Abstract
Background: More invasive retinoblastoma, characterized by increased morbidity and mortality, with lower rates of eye salvage and higher rates of extraocular dissemination, seems more prevalent in resource-poor countries. The relationship of diagnostic delay (lag time) and sociodemographic factors on the extent of disease at diagnosis has not been examined separately for unilateral and bilateral retinoblastoma.

Methods: At diagnosis, consenting parents of 179 Mexican children with retinoblastoma were interviewed about initial symptoms and household demographic characteristics. Clinical presentation was classified using St. Jude's, International Staging System (ISS), and International Intraocular Retinoblastoma Classification (IIRC) criteria. Lag time (delay between noting symptoms and diagnosis) and sociodemographic factors were examined as predictors for higher stage at diagnosis and overall survival (OS).

Results: In bilateral disease, lag time predicts stage at diagnosis using St. Jude's, and ISS criteria (P < 0.005 in multivariate regression), and OS (P < 0.05, Cox hazards), but not extent of intraocular disease (by IIRC). In unilateral disease, lag time predicts neither extent of disease (using ISS, St Jude's, and IIRC), nor OS. Indicators of prenatal poverty, including lower maternal education and the presence of dirt flooring in the home, predict more advanced disease by IIRC for bilateral retinoblastoma, and for unilateral by ISS, and St Jude's (P < 0.001) as well as OS (P < 0.05).

Conclusion: These results suggest unilateral and bilateral retinoblastoma differs in factors governing progression and extraretinal extension, possibly reflecting underlying biologic heterogeneity.

Impact: This demonstrates differing effect of social factors on extent of intra- and extraocular disease depending on laterality with implications for screening strategies. Cancer Epidemiol Biomarkers Prev; 23(5); 784–92. ©2014 AACR.
Data from Use of Antihypertensive Medications and Risk of Adverse Breast Cancer Outcomes in a SEER–Medicare Population
Authors: Chen Lu , Chubak Jessica , Boudreau Denise M. , Barlow William E. , Weiss Noel S. , Li Christopher I.
Published: April 2023

Abstract
Background: It is unclear if use of common antihypertensive medications influences the risk of adverse breast cancer outcomes.

Methods: Using the linked Surveillance, Epidemiology and End-Results (SEER)–Medicare database, we identified 14,766 women between ages 66 and 80 years diagnosed with incident stage I/II breast cancer between 2007 and 2011. Medicare Part D data were obtained to characterize women's post-cancer use of various antihypertensive medications. Outcomes included a second breast cancer event (SBCE; a composite outcome defined as the first of a recurrence or a second contralateral primary breast cancer), breast cancer recurrence, and breast cancer–specific mortality. Time-varying Cox proportional hazard models were used to estimate hazard ratios (HR) and their associated 95% confidence intervals (CI).

Results: There were 791 SBCEs, 627 breast cancer recurrences, and 237 breast cancer deaths identified over a median follow-up of 3 years. Use of diuretics (n = 8,517) after breast cancer diagnosis was associated with 29% (95% CI, 1.10–1.51), 36% (95% CI, 1.14–1.63) and 51% (95% CI, 1.11–2.04) higher risks of a SBCE, recurrence, and breast cancer death, respectively. Compared with nonusers, β-blockers users (n = 7,145) had a 41% (95% CI, 1.07–1.84) higher risk of breast cancer death. Use of angiotensin II receptor blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors were not associated with risks of breast cancer outcomes.

Conclusions: Use of diuretics and β-blockers may be associated with increased risk of breast cancer outcomes among older women.

Impact: Most antihypertensive medications are safe with respect to breast cancer outcomes, but more research is needed for diuretics and β-blockers. Cancer Epidemiol Biomarkers Prev; 26(11); 1603–10. ©2017 AACR.
Data from Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and ESR1 mRNA Expression in Breast Tumors
Authors: Butler Eboneé N. , Bensen Jeannette T. , Chen Mengjie , Conway Kathleen , Richardson David B. , Sun Xuezheng , Geradts Joseph , Olshan Andrew F. , Troester Melissa A.
Published: April 2023

Abstract
Background: Smoking is a possible risk factor for breast cancer and has been linked to increased risk of estrogen receptor–positive (ER+) disease in some epidemiologic studies. It is unknown whether smoking has quantitative effects on ER expression.

Methods: We examined relationships between smoking and ER expression from tumors of 1,888 women diagnosed with invasive breast cancer from a population-based study in North Carolina. ER expression was characterized using binary (±) and continuous measures for ER protein, ESR1 mRNA, and a multigene luminal score (LS) that serves as a measure of estrogen signaling in breast tumors. We used logistic and linear regression models to estimate temporal and dose-dependent associations between smoking and ER measures.

Results: The odds of ER+, ESR1+, and LS+ tumors among current smokers (at the time of diagnosis), those who smoked 20 or more years, and those who smoked within 5 years of diagnosis were nearly double those of nonsmokers. Quantitative levels of ESR1 were highest among current smokers compared with never smokers overall [mean (log2) = 9.2 vs. 8.7, P < 0.05] and among ER+ cases; however, we did not observe associations between smoking measures and continuous ER protein expression.

Conclusions: In relationship to breast cancer diagnosis, recent smoking was associated with higher odds of the ER+, ESR1+, and LS+ subtype. Current smoking was associated with elevated ESR1 mRNA levels and an elevated LS, but not with altered ER protein.

Impact: A multigene LS and single-gene ESR1 mRNA may capture tumor changes associated with smoking. Cancer Epidemiol Biomarkers Prev; 27(1); 67–74. ©2017 AACR.
Data from Age-Associated Gene Expression in Normal Breast Tissue Mirrors Qualitative Age-at-Incidence Patterns for Breast Cancer
Authors: Pirone Jason R. , D'Arcy Monica , Stewart Delisha A. , Hines William C. , Johnson Melissa , Gould Michael N. , Yaswen Paul , Jerry D. Joseph , Schneider Sallie Smith , Troester Melissa A.
Published: April 2023

Abstract
Background: Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women's breast cancer may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues.

Methods: To identify age-related changes in normal breast tissue, 96 tissue specimens from patients with reduction mammoplasty, ages 14 to 70 years, were assayed by gene expression microarray.

Results: Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included “aging of cells,” “shape change,” and “chemotaxis,” and enriched pathways included Wnt/beta-catenin signaling, Ephrin receptor signaling, and JAK/Stat signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival.

Conclusion: The hazard rates of young-like tumors mirrored that of high-grade tumors in the Surveillance, Epidemiology, and End Results Program, providing a biologic link between normal aging and age-related tumor aggressiveness.

Impact: These data show that studies of normal tissue gene expression can yield important insights about the pathways and biologic pressures that are relevant during tumor etiology and progression. Cancer Epidemiol Biomarkers Prev; 21(10); 1735–44. ©2012 AACR.
Data from Sociodemographic Inequalities in Sexual Activity and Cervical Cancer Screening: Implications for the Success of Human Papillomavirus Vaccination
Authors: Drolet Mélanie , Boily Marie-Claude , Greenaway Christina , Deeks Shelley L. , Blanchette Caty , Laprise Jean-François , Brisson Marc
Published: April 2023

Abstract
Background: Papanicolaou smear screening has significantly reduced cervical cancer morbidity and mortality. However, inequalities still persist across different socioeconomic status (SES) groups. These inequalities have been associated with differential participation in screening. However, even with equal participation to screening, some women may still have greater risk of cervical cancer because of sexual behavior. We aim to identify the sociodemographic characteristics of women who reported greater sexual activity and/or screening underuse.

Methods: We used data from (i) the Canadian Community Health Survey—2005, a population-based survey of 130,000 Canadians, and (ii) a multicenter study including 952 women screened for cervical cancer.

Results: Aboriginals and women with lower SES reported greater sexual activity and lower screening participation, which may produce synergetic effects toward higher cervical cancer risk. Women who did not complete high school and aboriginals were, respectively, 3.6 and 2.5 times more likely to report sexual debut before 15 years old compared with women with university degree and Caucasians. Women who did not complete high school were 2.2 times more likely to have never been screened compared with women with university degree. East and South Asian women were, respectively, 4.3 and 3.1 times more likely to have never been screened than Canadian-born women but reported lower levels of sexual activity and were adherent to screening guidelines when screened at least once.

Conclusions: The success of human papillomavirus vaccination at reducing cervical cancer and inequalities will depend on achieving high coverage among high-risk subpopulations.

Impact: These groups must be monitored closely, and if need be, targeted for additional interventions. Cancer Epidemiol Biomarkers Prev; 22(4); 641–52. ©2013 AACR.
Data from A Population-Based Evaluation of Cervical Screening in the United States: 2008–2011
Authors: Cuzick Jack , Myers Orrin , Hunt William C. , Robertson Michael , Joste Nancy E. , Castle Philip E. , Benard Vicki B. , Wheeler Cosette M.
Published: April 2023

Abstract
Background: Cervical screening consumes substantial resources, but little is known about utilization in the United States or compliance with guideline recommendations.

Methods: To describe population screening coverage, utilization, and outcomes and examine time trends from 2008 to 2011, cervical cytology reports from women residing in New Mexico (981,063 tests from 511,381 women) were evaluated.

Results: From 2008 to 2011 cervical screening utilization decreased at all ages, but especially in younger women, with a two-third reduction at ages 15 to 20 years. Ninety-four percent of women ages 25 to 29 years were screened within 48 months but coverage decreased at older ages to 69% at 45 to 49 years and 55% at 60 to 64 years. Intervals between screening tests were significantly longer in 2011 compared with 2008 [HR = 1.23; 95% confidence intervals (CI), 1.22–1.24], although the commonest rescreening interval was 13 months. In 2011, 91.9% of screening tests for women ages 21 to 65 years were negative, 6.6% showed minor abnormalities, and 1.0% high-grade abnormalities. High-grade abnormality rates were relatively constant over time, but minor abnormalities and atypical cells cannot rule out high-grade (ASC-H) were increasing.

Conclusions: This population-based evaluation of cervical screening shows high coverage under the age of 40 years, but lower levels in older women. Screening under age 21 years is becoming less common and screening intervals are lengthening, reflecting updates in national screening guidelines.

Impact: Assessment of cervical screening intervals and population outcomes is essential for accurately estimating the impact and effectiveness of changing recommendations and vaccination against human papilloma virus infections. Cancer Epidemiol Biomarkers Prev; 23(5); 765–73. ©2013 AACR.
Data from Estimated Mean Sojourn Time Associated with Hemoccult SENSA for Detection of Proximal and Distal Colorectal Cancer
Authors: Zheng Wenying , Rutter Carolyn M.
Published: April 2023

Abstract
Background: Sojourn time is the length of the preclinical screen-detectable phase, a period when a test can detect asymptomatic disease. Mean sojourn time (MST) is an important factor in determining appropriate screening intervals. Available estimates of MST for colorectal cancer (CRC) are imprecise and are associated with the older Hemoccult II test. This article presents MST estimates associated with the newer Hemoccult SENSA test and describes differences in MST by the location of cancer in the colorectum and age at the time of screening.

Methods: MST was estimated from a cohort of 42,079 patients who underwent Hemoccult SENSA between January 1, 1997 and December 31, 2010. The precision of MST estimates was improved by incorporating information from a meta-analysis of the sensitivity of Hemoccult SENSA into the analytic model.

Results: Estimated MST for cancers in the proximal and distal colorectum, with 95% credible intervals (CrI) in years, were: 3.86 (1.55–6.91) and 3.35 (2.11–4.93) among 45- to 54-year olds; 3.78 (2.18–5.77) and 2.24 (1.48–3.17) among 55- to 64-year olds; and 2.70 (1.41–4.31) and 2.10 (1.34–3.04) among 65- to 74-year olds.

Conclusions: MST associated with Hemoccult SENSA was longer for CRC in the proximal versus distal colon. We found no evidence that MST increases with age and some evidence that it may decrease.

Impact: These results add new information about the natural history of CRC and information about the performance of Hemoccult SENSA. Cancer Epidemiol Biomarkers Prev; 21(10); 1722–30. ©2012 AACR.
Data from Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII
Authors: Merritt Melissa A. , Tzoulaki Ioanna , Tworoger Shelley S. , De Vivo Immaculata , Hankinson Susan E. , Fernandes Judy , Tsilidis Konstantinos K. , Weiderpass Elisabete , Tjønneland Anne , Petersen Kristina E.N. , Dahm Christina C. , Overvad Kim , Dossus Laure , Boutron-Ruault Marie-Christine , Fagherazzi Guy , Fortner Renée T. , Kaaks Rudolf , Aleksandrova Krasimira , Boeing Heiner , Trichopoulou Antonia , Bamia Christina , Trichopoulos Dimitrios , Palli Domenico , Grioni Sara , Tumino Rosario , Sacerdote Carlotta , Mattiello Amalia , Bueno-de-Mesquita H.B(as). , Onland-Moret N. Charlotte , Peeters Petra H. , Gram Inger T. , Skeie Guri , Quirós J. Ramón , Duell Eric J. , Sánchez María-José , Salmerón D. , Barricarte Aurelio , Chamosa Saioa , Ericson Ulrica , Sonestedt Emily , Nilsson Lena Maria , Idahl Annika , Khaw Kay-Tee , Wareham Nicholas , Travis Ruth C. , Rinaldi Sabina , Romieu Isabelle , Patel Chirag J. , Riboli Elio , Gunter Marc J.
Published: April 2023

Abstract
Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a “nutrient-wide association study” approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR ≤ 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68–0.97, Ptrend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70–0.96, Ptrend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. Cancer Epidemiol Biomarkers Prev; 24(2); 466–71. ©2015 AACR.
Data from Drinking Water Arsenic in Northern Chile: High Cancer Risks 40 Years after Exposure Cessation
Authors: Steinmaus Craig M. , Ferreccio Catterina , Romo Johanna Acevedo , Yuan Yan , Cortes Sandra , Marshall Guillermo , Moore Lee E. , Balmes John R. , Liaw Jane , Golden Todd , Smith Allan H.
Published: April 2023

Abstract
Background: Millions of people worldwide are exposed to arsenic-contaminated water. In the largest city in northern Chile (Antofagasta), more than 250,000 people were exposed to high arsenic drinking water concentrations from 1958 until 1970 when a water treatment plant was installed. Because of its unique geology, limited water sources, and good historical records, lifetime exposure and long-term latency patterns can be assessed in this area with better accuracy than in other arsenic-exposed areas worldwide.

Methods: We conducted a population-based case–control study in northern Chile from October 2007 to December 2010 involving 232 bladder and 306 lung cancer cases and 640 age- and gender-matched controls, with detailed information on past exposure and potential confounders, including smoking and occupation.

Results: Bladder cancer ORs for quartiles of average arsenic concentrations in water before 1971 (<11, 11–90, 91–335, and >335 μg/L) were 1.00, 1.36 [95% confidence interval (CI), 0.78–2.37], 3.87 (2.25–6.64), and 6.50 (3.69–11.43), respectively. Corresponding lung cancer ORs were 1.00, 1.27 (0.81–1.98), 2.00 (1.24–3.24), and 4.32 (2.60–7.17). Bladder and lung cancer ORs in those highly exposed in Antofagasta during 1958 to 1970 but not thereafter were 6.88 (3.84–12.32) and 4.35 (2.57–7.36), respectively.

Conclusions: The lung and bladder cancer risks that we found up to 40 years after high exposures have ended are very high.

Impact: Our findings suggest that prevention, treatment, and other mortality reduction efforts in arsenic-exposed countries will be needed for decades after exposure cessation. Cancer Epidemiol Biomarkers Prev; 22(4); 623–30. ©2013 AACR.
Data from Physical Activity and Risk of Lymphoma: A Meta-Analysis
Authors: Vermaete Nele V.H. , Wolter Pascal , Verhoef Gregor E.G. , Kollen Boudewijn J. , Kwakkel Gert , Schepers Leen , Gosselink Rik
Published: April 2023

Abstract
Background: Physical activity has a protective effect on some types of cancer. The aim of the present meta-analysis was to explore the literature on the association between physical activity and risk of lymphoma.

Methods: A meta-analysis was conducted for cohort and case–control studies examining the association between self-reported physical activity and risk of lymphoma. Depending on statistical heterogeneity, a random or fixed effects model was used to estimate the summary OR and corresponding 95% confidence interval (CI).

Results: Seven case–control studies and 5 cohort studies were included. When data from both study designs were combined, no significant influence of physical activity on risk of lymphoma was found (pooled OR = 0.90; 95% CI: 0.79–1.02; P = 0.10). Subgroup analysis revealed a significant protective influence of physical activity on risk of lymphoma in case–control studies (pooled OR = 0.81; 95% CI: 0.68–0.96; P = 0.02). In contrast, cohort studies, which have a higher level of evidence than case–control studies, confirm the results of the primary meta-analysis (pooled OR = 1.02; 95% CI: 0.88–1.19; P = 0.76). A subsequent subgroup analysis found no significant differences between results for Hodgkin lymphoma and non-Hodgkin lymphoma (χ2 = 0.16; P = 0.69), nor between results for recreational and occupational activities (χ2 = 1.01; P = 0.31).

Conclusions: Epidemiologic research indicates no significant influence of physical activity on risk of lymphoma.

Impact: Future research should examine the association between sedentary behavior and risk of lymphoma and investigate the dose–response and timing effect of physical activity on risk of lymphoma. Cancer Epidemiol Biomarkers Prev; 22(7); 1173–84. ©2013 AACR.
Data from Compensatory Smoking from Gradual and Immediate Reduction in Cigarette Nicotine Content
Authors: Hatsukami Dorothy K. , Donny Eric C. , Koopmeiners Joseph S. , Benowitz Neal L.
Published: April 2023

Abstract
Reducing the addictiveness of cigarettes by reducing their nicotine content can potentially have a profound impact on public health. Two different approaches to nicotine reduction have been proposed: gradual and immediate. To determine if either of these approaches results in significant compensatory smoking behavior, which might lead to safety concerns, we performed a secondary analysis of data from studies that have utilized these two approaches. The number of cigarettes smoked per day, carbon monoxide exposure, and cotinine levels in plasma or urine were assessed while participants smoked reduced nicotine content cigarettes and compared with when they smoked their usual brand cigarettes. The results showed that in general, these two approaches led to minimal compensatory smoking and reduced levels of cotinine over the course of the experimental period, suggesting that neither of these approaches poses a major safety concern. Cancer Epidemiol Biomarkers Prev; 24(2); 472–6. ©2014 AACR.
Data from Costs Associated with Management of Cervical Human Papillomavirus-Related Conditions
Authors: Kruzikas Denise , Smith Jennifer S. , Harley Carolyn , Buzinec Paul
Published: April 2023

Abstract
Background: Oncogenic types of human papillomavirus (HPV) have been linked to 99.7% of cervical cancer cases worldwide.

Methods: This retrospective claims-based analysis was conducted to assess patterns of use and costs associated with diagnostic and treatment procedures for disease attributed to HPV performed before the introduction of HPV vaccination (January 1, 2001–May 31, 2006). Percentages of commercially insured health plan enrollees who underwent each procedure of interest were calculated for each year. Annual costs (combined patient and health plan-paid amounts) were calculated from qualifying medical claims. Descriptive statistics were used to assess trends in procedure rates and costs.

Results: Data for approximately 14.2 million enrollees were obtained. Hysterectomy was the most commonly administered treatment. With the exception of colposcopy with LEEP, all other treatment procedures experienced a decline in rate of use. The most frequently performed diagnostic procedure was colposcopy with endocervical curettage (ECC). With the exception of ECC, rates of diagnostic procedures reached a peak among 20- to 24-year-olds, and followed a downward trend across older groups. Hysterectomy was the most expensive treatment (median $7,383; mean $8,384) per procedure in 2006.

Conclusion: Results reveal high rates of use and high-associated costs of diagnostic procedures and treatments related to disease attributed to HPV.

Impact: The data presented may be useful in cost-effectiveness analyses and to guide decision makers evaluating how best to optimize prevention strategies. Cancer Epidemiol Biomarkers Prev; 21(9); 1469–78. ©2012 AACR.
Data from Comprehensive Evaluation of Medical Conditions Associated with Risk of Non-Hodgkin Lymphoma using Medicare Claims (“MedWAS”)
Authors: Engels Eric A. , Parsons Ruth , Besson Caroline , Morton Lindsay M. , Enewold Lindsey , Ricker Winnie , Yanik Elizabeth L. , Arem Hannah , Austin April A. , Pfeiffer Ruth M.
Published: April 2023

Abstract
Background: Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method (“medical condition-wide association study,” MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims.

Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we conducted a case–control study comparing NHL cases [N = 52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma (MZL), T-cell lymphoma (TCL)] to controls (N = 200,000). We systematically screened for associations with 5,926 medical conditions documented in Medicare claims more than 1 year before selection.

Results: Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (ORs 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of nonmelanoma skin cancer (ORs 1.19–1.55), actinic keratosis (1.12–1.25), or hemolytic anemia (1.64–4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20–4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%).

Conclusion: Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes.

Impact: These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1105–13. ©2016 AACR.
Data from Prevalidation of Salivary Biomarkers for Oral Cancer Detection
Authors: Elashoff David , Zhou Hui , Reiss Jean , Wang Jianghua , Xiao Hua , Henson Bradley , Hu Shen , Arellano Martha , Sinha Uttam , Le Anh , Messadi Diana , Wang Marilene , Nabili Vishad , Lingen Mark , Morris Darly , Randolph Timothy , Feng Ziding , Akin David , Kastratovic Dragana A. , Chia David , Abemayor Elliot , Wong David T.W.
Published: April 2023

Abstract
Background: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL).

Methods: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL.

Results: Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts.

Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies.

Impact: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. Cancer Epidemiol Biomarkers Prev; 21(4); 664–72. ©2012 AACR.
Data from Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium
Authors: Williams Lindsay A. , Olshan Andrew F. , Hong Chi-Chen , Bandera Elisa V. , Rosenberg Lynn , Cheng Ting-Yuan David , Lunetta Kathryn L. , McCann Susan E. , Poole Charles , Kolonel Laurence N. , Palmer Julie R. , Ambrosone Christine B. , Troester Melissa A.
Published: April 2023

Abstract
Background: Alcohol is a recognized risk factor for invasive breast cancer, but few studies involve African American women.

Methods: The current analysis included 22,338 women (5,108 cases of invasive breast cancer) from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. The association between number of alcoholic drinks per week (dpw) and breast cancer was estimated using logistic regression, adjusting for potential confounders, and stratifying by breast cancer subtype.

Results: Approximately 35% of controls were current drinkers at interview. Women who reported current drinking of ≥14 dpw had an elevated risk of breast cancer compared with light drinkers (>0–<4 dpw) [adjusted OR (ORadj), 1.33; 95% confidence interval (CI), 1.07–1.64]. We observed elevated risk among women drinking ≥7 dpw for ER− [ORadj, 1.31; 95% CI, 1.00–1.72], PR− [ORadj, 1.28; 95% CI, 1.00–1.63], HER2− [ORadj, 1.36; 95% CI, 1.09–1.70], and triple-negative [ORadj, 1.39; 95% CI, 0.98–2.00] molecular subtype. Among receptor-positive cases, ORs remained elevated but attenuated relative to receptor-negative cases. Sensitivity analysis of age-defined windows of exposure (<30 years, 30–49, 50+ years of age) did not reveal variation in patterns of association. Risk associated with alcohol intake did not vary significantly by oral contraceptive use, smoking status, or menopausal status.

Conclusions: Among African American women, similar to women of European descent, drinking ≥7 alcoholic dpw was associated with an increased risk of breast cancer regardless of subtype.

Impact: Alcohol intake is a modifiable risk factor for breast cancer, and reduced intake among African American women should be encouraged. Cancer Epidemiol Biomarkers Prev; 26(5); 787–94. ©2017 AACR.
Data from Prevalence of Major Risk Factors and Use of Screening Tests for Cancer in the United States
Authors: Fedewa Stacey A. , Sauer Ann Goding , Siegel Rebecca L. , Jemal Ahmedin
Published: April 2023

Abstract
Much of the suffering and death from cancer could be prevented by more systematic efforts to reduce tobacco use, improve diet, increase physical activity, reduce obesity, and expand the use of established screening tests. Monitoring the prevalence of cancer risk factors and screening is important to measure progress and strengthen cancer prevention and early detection efforts. In this review article, we provide recent prevalence estimates for several cancer risk factors, including tobacco, obesity, physical activity, nutrition, ultraviolet radiation exposure as well as human papillomavirus and hepatitis B vaccination coverage and cancer screening prevalence in the United States. In 2013, cigarette smoking prevalence was 17.8% among adults nationally, but ranged from 10.3% in Utah to 27.3% in West Virginia. In addition, 15.7% of U.S. high school students were current smokers. In 2011–2012, obesity prevalence was high among both adults (34.9%) and adolescents (20.5%), but has leveled off since 2002. About 20.2% of high school girls were users of indoor tanning devices, compared with 5.3% of boys. In 2013, cancer screening prevalence ranged from 58.6% for colorectal cancer to 80.8% for cervical cancer and remains low among the uninsured, particularly for colorectal cancer screening where only 21.9% of eligible adults received recommended colorectal cancer screening. Cancer Epidemiol Biomarkers Prev; 24(4); 637–52. ©2015 AACR.
Data from Inherited Genetic Variants Associated with Occurrence of Multiple Primary Melanoma
Authors: Gibbs David C. , Orlow Irene , Kanetsky Peter A. , Luo Li , Kricker Anne , Armstrong Bruce K. , Anton-Culver Hoda , Gruber Stephen B. , Marrett Loraine D. , Gallagher Richard P. , Zanetti Roberto , Rosso Stefano , Dwyer Terence , Sharma Ajay , La Pilla Emily , From Lynn , Busam Klaus J. , Cust Anne E. , Ollila David W. , Begg Colin B. , Berwick Marianne , Thomas Nancy E.
Published: April 2023

Abstract
Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case–control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. Cancer Epidemiol Biomarkers Prev; 24(6); 992–7. ©2015 AACR.
Data from Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm
Authors: Sun Xiangqing , Elston Robert C. , Barnholtz-Sloan Jill S. , Falk Gary W. , Grady William M. , Faulx Ashley , Mittal Sumeet K. , Canto Marcia , Shaheen Nicholas J. , Wang Jean S. , Iyer Prasad G. , Abrams Julian A. , Tian Ye D. , Willis Joseph E. , Guda Kishore , Markowitz Sanford D. , Chandar Apoorva , Warfe James M. , Brock Wendy , Chak Amitabh
Published: April 2023

Abstract
Background: Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed.

Methods: We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees.

Results: Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy.

Conclusions: Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information.

Impact: Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 25(5); 727–35. ©2016 AACR.
Data from Contribution of Screening and Survival Differences to Racial Disparities in Colorectal Cancer Rates
Authors: Lansdorp-Vogelaar Iris , Kuntz Karen M. , Knudsen Amy B. , van Ballegooijen Marjolein , Zauber Ann G. , Jemal Ahmedin
Published: April 2023

Abstract
Background: Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the United States. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival.

Methods: We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks, aged 50 years and older, from 1975 to 2007 assuming they had: (i) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); (ii) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and (iii) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates.

Results: Differences in screening accounted for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. Thirty-six percent of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little more than 50% of the disparity in CRC mortality between blacks and whites.

Conclusion: Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites.

Impact: Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden. Cancer Epidemiol Biomarkers Prev; 21(5); 728–36. ©2012 AACR.
Data from Serum Levels of the Chemokine CXCL13, Genetic Variation in CXCL13 and Its Receptor CXCR5, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk
Authors: Hussain Shehnaz K. , Zhu Weiming , Chang Shen-Chih , Breen Elizabeth Crabb , Vendrame Elena , Magpantay Larry , Widney Dan , Conn Daniel , Sehl Mary , Jacobson Lisa P. , Bream Jay H. , Wolinsky Steven , Rinaldo Charles R. , Ambinder Richard F. , Detels Roger , Zhang Zuo-Feng , Martínez-Maza Otoniel
Published: April 2023

Abstract
Background: CXCL13 and CXCR5 are a chemokine and receptor pair whose interaction is critical for naïve B-cell trafficking and activation within germinal centers. We sought to determine whether CXCL13 levels are elevated before HIV-associated non-Hodgkin B-cell lymphoma (AIDS-NHL), and whether polymorphisms in CXCL13 or CXCR5 are associated with AIDS-NHL risk and CXCL13 levels in a large cohort of HIV-infected men.

Methods: CXCL13 levels were measured in sera from 179 AIDS-NHL cases and 179 controls at three time-points. TagSNPs in CXCL13 (n = 16) and CXCR5 (n = 11) were genotyped in 183 AIDS-NHL cases and 533 controls. OR and 95% confidence intervals (CI) for the associations between one unit increase in log CXCL13 levels and AIDS-NHL, as well as tagSNP genotypes and AIDS-NHL, were computed using logistic regression. Mixed linear regression was used to estimate mean ratios (MR) for the association between tagSNPs and CXCL13 levels.

Results: CXCL13 levels were elevated for more than 3 years (OR = 3.24; 95% CI = 1.90–5.54), 1 to 3 years (OR = 3.39; 95% CI = 1.94–5.94), and 0 to 1 year (OR = 3.94; 95% CI = 1.98–7.81) before an AIDS-NHL diagnosis. The minor allele of CXCL13 rs355689 was associated with reduced AIDS-NHL risk (ORTCvsTT = 0.65; 95% CI = 0.45–0.96) and reduced CXCL13 levels (MRCCvsTT = 0.82; 95% CI = 0.68–0.99). The minor allele of CXCR5 rs630923 was associated with increased CXCL13 levels (MRAAvsTT = 2.40; 95% CI = 1.43–4.50).

Conclusions: CXCL13 levels were elevated preceding an AIDS-NHL diagnosis, genetic variation in CXCL13 may contribute to AIDS-NHL risk, and CXCL13 levels may be associated with genetic variation in CXCL13 and CXCR5.

Impact: CXCL13 may serve as a biomarker for early AIDS-NHL detection. Cancer Epidemiol Biomarkers Prev; 22(2); 295–307. ©2012 AACR.