Pub Date : 2024-09-30DOI: 10.1158/1055-9965.EPI-24-0744
Chelsea Duong, Erik J Rodriquez, Amanda S Hinerman, Somy Hooshmand, Sophie E Claudel, Neal L Benowitz, Eliseo J Perez-Stable
Background: Tobacco biomarkers reflect smoking intensity and are used to assess cessation status. No study has evaluated variation by Latino heritage.
Methods: Data from the 2007-2014 National Health and Nutrition Examination Survey were used to evaluate geometric mean concentrations of serum cotinine and urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), stratified by smoking status and race and ethnicity, and receiver operating characteristic curves estimated values to distinguish smokers from non-smokers by race and ethnicity and Latino heritage.
Results: The sample (n=18,597) was 50.1% female, 16.6% Latino (58.6% Mexican, 10.4% Central American, 9.1% South American, 7.3% Puerto Rican, 3.5% Dominican, 2.7% Cuban, 8.4% Other Latinos, overall), 12.7% Black, and 70.7% White. Black non-smokers and smokers had the highest cotinine concentrations (0.1 ng/mL and 177.1 ng/mL) and among non-smokers, Black individuals had the highest NNAL concentrations (1.4 pg/mL). Latino smokers had the lowest cotinine (32.7 ng/mL) and NNAL (63.9 pg/mL) concentrations. Among Latino smokers, Puerto Rican individuals had higher concentrations of cotinine (100.0 ng/mL) and NNAL (136.4 pg/mL). Cotinine levels defining smoking (Black: 9.1 ng/mL, Latino: 0.9 ng/mL, White: 3.8 ng/mL) and NNAL (Black: 24.1 pg/mL, Latino: 5.7 pg/mL, White: 15.5 pg/mL) varied. Puerto Rican adults (cotinine: 8.5 ng/mL, NNAL: 17.2 pg/mL) had higher levels than Central American (cotinine: 1.0 ng/mL, NNAL: 5.5 pg/mL) and Mexican (cotinine: 0.9 ng/mL, NNAL: 6.0 pg/mL) adults.
Conclusions: Cotinine and NNAL concentrations that define smoking differed by race and ethnicity and by heritage among Latinos, showing meaningful differences.
Impact: Cessation interventions with biomarker validation need to consider Latino heritage.
{"title":"Tobacco Biomarkers by Latino Heritage and Race, U.S., 2007-2014 National Health and Nutrition Examination Survey.","authors":"Chelsea Duong, Erik J Rodriquez, Amanda S Hinerman, Somy Hooshmand, Sophie E Claudel, Neal L Benowitz, Eliseo J Perez-Stable","doi":"10.1158/1055-9965.EPI-24-0744","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-24-0744","url":null,"abstract":"<p><strong>Background: </strong>Tobacco biomarkers reflect smoking intensity and are used to assess cessation status. No study has evaluated variation by Latino heritage.</p><p><strong>Methods: </strong>Data from the 2007-2014 National Health and Nutrition Examination Survey were used to evaluate geometric mean concentrations of serum cotinine and urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), stratified by smoking status and race and ethnicity, and receiver operating characteristic curves estimated values to distinguish smokers from non-smokers by race and ethnicity and Latino heritage.</p><p><strong>Results: </strong>The sample (n=18,597) was 50.1% female, 16.6% Latino (58.6% Mexican, 10.4% Central American, 9.1% South American, 7.3% Puerto Rican, 3.5% Dominican, 2.7% Cuban, 8.4% Other Latinos, overall), 12.7% Black, and 70.7% White. Black non-smokers and smokers had the highest cotinine concentrations (0.1 ng/mL and 177.1 ng/mL) and among non-smokers, Black individuals had the highest NNAL concentrations (1.4 pg/mL). Latino smokers had the lowest cotinine (32.7 ng/mL) and NNAL (63.9 pg/mL) concentrations. Among Latino smokers, Puerto Rican individuals had higher concentrations of cotinine (100.0 ng/mL) and NNAL (136.4 pg/mL). Cotinine levels defining smoking (Black: 9.1 ng/mL, Latino: 0.9 ng/mL, White: 3.8 ng/mL) and NNAL (Black: 24.1 pg/mL, Latino: 5.7 pg/mL, White: 15.5 pg/mL) varied. Puerto Rican adults (cotinine: 8.5 ng/mL, NNAL: 17.2 pg/mL) had higher levels than Central American (cotinine: 1.0 ng/mL, NNAL: 5.5 pg/mL) and Mexican (cotinine: 0.9 ng/mL, NNAL: 6.0 pg/mL) adults.</p><p><strong>Conclusions: </strong>Cotinine and NNAL concentrations that define smoking differed by race and ethnicity and by heritage among Latinos, showing meaningful differences.</p><p><strong>Impact: </strong>Cessation interventions with biomarker validation need to consider Latino heritage.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1158/1055-9965.EPI-24-0717
Holly R Harris, Kathylynn Saboda, Cynthia A Thomson, Nazmus Saquib, Aladdin H Shadyab, Peter F Schnatz, Rogelio Robles-Morales, Lihong Qi, Denise J Roe, Leslie V Farland
Background: Several studies have suggested an association between infertility and risk of endometrial cancer. However, most studies have evaluated this relationship in premenopausal people, yet the mean age of endometrial cancer is 60 years old, after the average age of menopause.
Methods: Our study included Women's Health Initiative participants who self-reported whether they had a history of infertility. Cox proportional hazards models were used to examine the association between infertility and incident endometrial cancer. Given that all infertility diagnoses occurred prior to study enrollment, we conducted secondary analyses using logistic regression examining prevalent endometrial cancer cases diagnosed before study baseline.
Results: Approximately 18% of participants reported a history of infertility. No statistically significant association was observed between infertility and risk of incident endometrial cancer overall (incident cases=1622; hazard ratio [HR]=1.12; 95% confidence interval [CI]=0.99-1.26). While point estimates suggested an increase in risk of endometrial cancer among women with BMI ≥25 (HR=1.15; 95% CI=0.99-1.33), none of the associations were statistically significant. There was an association between history of infertility and prevalent endometrial cancer cases (odds ratio [OR]=1.19; 95% CI=1.06-1.34), with the strongest association for infertility diagnosis due to endometriosis (OR=2.42; 95% CI=1.83-3.19).
Conclusions: In a population of postmenopausal participants, we observed a modest, but not statistically significant, association between overall infertility and incident endometrial cancer, with the suggestion of a higher risk among those with a BMI ≥25.
Impact: Our findings highlight, as observed in previous studies, that risk factors for endometrial cancer may vary by body mass index.
{"title":"History of infertility and risk of endometrial cancer in the Women's Health Initiative.","authors":"Holly R Harris, Kathylynn Saboda, Cynthia A Thomson, Nazmus Saquib, Aladdin H Shadyab, Peter F Schnatz, Rogelio Robles-Morales, Lihong Qi, Denise J Roe, Leslie V Farland","doi":"10.1158/1055-9965.EPI-24-0717","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-24-0717","url":null,"abstract":"<p><strong>Background: </strong>Several studies have suggested an association between infertility and risk of endometrial cancer. However, most studies have evaluated this relationship in premenopausal people, yet the mean age of endometrial cancer is 60 years old, after the average age of menopause.</p><p><strong>Methods: </strong>Our study included Women's Health Initiative participants who self-reported whether they had a history of infertility. Cox proportional hazards models were used to examine the association between infertility and incident endometrial cancer. Given that all infertility diagnoses occurred prior to study enrollment, we conducted secondary analyses using logistic regression examining prevalent endometrial cancer cases diagnosed before study baseline.</p><p><strong>Results: </strong>Approximately 18% of participants reported a history of infertility. No statistically significant association was observed between infertility and risk of incident endometrial cancer overall (incident cases=1622; hazard ratio [HR]=1.12; 95% confidence interval [CI]=0.99-1.26). While point estimates suggested an increase in risk of endometrial cancer among women with BMI ≥25 (HR=1.15; 95% CI=0.99-1.33), none of the associations were statistically significant. There was an association between history of infertility and prevalent endometrial cancer cases (odds ratio [OR]=1.19; 95% CI=1.06-1.34), with the strongest association for infertility diagnosis due to endometriosis (OR=2.42; 95% CI=1.83-3.19).</p><p><strong>Conclusions: </strong>In a population of postmenopausal participants, we observed a modest, but not statistically significant, association between overall infertility and incident endometrial cancer, with the suggestion of a higher risk among those with a BMI ≥25.</p><p><strong>Impact: </strong>Our findings highlight, as observed in previous studies, that risk factors for endometrial cancer may vary by body mass index.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1158/1055-9965.EPI-24-1091
Antoine Dubray-Vautrin, Guillaume Rougier, Christophe Le Tourneau, Wahib Ghanem, Nathalie Badois, Maria Lesnik, Baptiste Sabran, Laurence Bozec, Joey Martin, Olivier Choussy
Squamous cell carcinomas (SCCs) of the oral cavity in young adults represent a heterogeneous entity. New prognostic biomarkers are described in the literature. The aim was to identify emerging biomarkers and prognostic stratification factors of young population. Clinical, biological, microbiological, histopathological, and molecular markers statistically associated with overall and disease-free survival (OS) and validated in literature. Young adults < 40 years who were non-smokers showed a marginally worse prognosis, while age < 30 years was unfavorable compared to > 30 years. High rate of Neutrophil-to-lymphocyte ratio (NLR) was associated with decreased 5-year disease-specific survival, PDL1 expression correlated with improved OS and recurrence-free survival, presence of Fusobacterium, Mutations in p53, Cyclin D1, and VEGF was associated with reduced OS. Combining these markers in young adult oral cavity SCCs should be used to adapt the intensification of therapy in addition to the TNM classification and minor histo-prognostic factors.
{"title":"Biomarkers and Prognostic Stratification of Squamous Cell Carcinoma of the Oral Cavity in Young Adults: how to personalize therapeutic management?","authors":"Antoine Dubray-Vautrin, Guillaume Rougier, Christophe Le Tourneau, Wahib Ghanem, Nathalie Badois, Maria Lesnik, Baptiste Sabran, Laurence Bozec, Joey Martin, Olivier Choussy","doi":"10.1158/1055-9965.EPI-24-1091","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-24-1091","url":null,"abstract":"<p><p>Squamous cell carcinomas (SCCs) of the oral cavity in young adults represent a heterogeneous entity. New prognostic biomarkers are described in the literature. The aim was to identify emerging biomarkers and prognostic stratification factors of young population. Clinical, biological, microbiological, histopathological, and molecular markers statistically associated with overall and disease-free survival (OS) and validated in literature. Young adults < 40 years who were non-smokers showed a marginally worse prognosis, while age < 30 years was unfavorable compared to > 30 years. High rate of Neutrophil-to-lymphocyte ratio (NLR) was associated with decreased 5-year disease-specific survival, PDL1 expression correlated with improved OS and recurrence-free survival, presence of Fusobacterium, Mutations in p53, Cyclin D1, and VEGF was associated with reduced OS. Combining these markers in young adult oral cavity SCCs should be used to adapt the intensification of therapy in addition to the TNM classification and minor histo-prognostic factors.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1158/1055-9965.epi-24-0488
Oumarou Nabi, Ying Liu, James Struthers, Min Lian
Background: It remains unclear if residential segregation impacts on clinical treatment and outcomes for ductal carcinoma in situ (DCIS), a nonobligate precursor to invasive breast cancer (IBC). Methods: This population-based retrospective cohort study included adult non-Hispanic White (NHW) and Black (NHB) women diagnosed with unilateral DCIS between January 1990 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. County-level racialized economic segregation was measured using the Index of Concentration at the Extremes. Multilevel logistic regression and Cox proportional hazards regression accounting for county-level clustering were used to estimate the odds ratios (ORs) of local treatment, and hazard ratios (HRs) of subsequent IBC and mortality. Results: Of 103,898 cases, mean age was 59.5 years, 12.5% were NHB, 87.5% were NHW, 97.5% underwent surgery, 64.5% received radiotherapy following breast-conserving surgery, 7.1% developed IBC, and 18.6% died from all causes. Among women living in the least vs most privileged counties, we observed higher odds of receiving mastectomy (vs breast-conserving surgery) (OR=1.51, 95% CI 1.35-1.69; Ptrend<0.001) and radiation therapy following breast-conserving surgery (OR=1.27, 95% CI 1.07-1.51; Ptrend<0.01); the risk was higher in subsequent ipsilateral IBC (HR=1.16, 95% CI 1.02-1.32; Ptrend=0.04), not in breast cancer-specific mortality (HR=1.04, 95% CI 0.88-1.23; Ptrend=0.56). Conclusions: The results provide evidence for disparities in clinical treatment for DCIS and prognostic outcomes among women in racially and economically segregated counties. Impact: Our findings may inform geographically targeted multilevel interventions to reduce breast cancer burden and improve breast cancer care and equity.
背景：乳腺导管原位癌（DCIS）是侵袭性乳腺癌（IBC）的非潜在前体，目前尚不清楚居住地隔离是否会影响其临床治疗和预后。研究方法这项基于人群的回顾性队列研究纳入了1990年1月至2015年12月期间被诊断为单侧DCIS的非西班牙裔白人（NHW）和黑人（NHB）成年女性，随访至2016年12月，并从 "监测、流行病学和最终结果 "数据集中识别。县级种族化经济隔离采用极端集中指数（Index of Concentration at the Extremmes）进行测量。多层次逻辑回归和考克斯比例危害回归考虑了县级聚类，用于估计当地治疗的几率比（ORs）以及后续 IBC 和死亡率的危害比（HRs）。结果：在 103,898 个病例中，平均年龄为 59.5 岁，12.5% 为非华裔女性，87.5% 为非华裔女性，97.5% 接受了手术，64.5% 在保乳手术后接受了放疗，7.1% 发展为 IBC，18.6% 死于各种原因。在生活条件最差的县与生活条件最好的县的妇女中，我们观察到接受乳房切除术（与保乳手术相比）（OR=1.51，95% CI 1.35-1.69；Ptrend<0.001）和保乳手术后接受放射治疗（OR=1.27，95% CI 1.07-1.51；Ptrend<0.01）；随后同侧 IBC 的风险更高（HR=1.16，95% CI 1.02-1.32；Ptrend=0.04），而乳腺癌特异性死亡率（HR=1.04，95% CI 0.88-1.23；Ptrend=0.56）则不高。结论研究结果证明，在种族和经济隔离县的妇女中，DCIS 的临床治疗和预后结果存在差异。影响：我们的研究结果可为有地域针对性的多层次干预措施提供信息，以减轻乳腺癌负担并改善乳腺癌护理和公平性。
{"title":"The Role of Residential Segregation in Treatment and Outcomes of Ductal Carcinoma in Situ of the Breast","authors":"Oumarou Nabi, Ying Liu, James Struthers, Min Lian","doi":"10.1158/1055-9965.epi-24-0488","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0488","url":null,"abstract":"Background: It remains unclear if residential segregation impacts on clinical treatment and outcomes for ductal carcinoma in situ (DCIS), a nonobligate precursor to invasive breast cancer (IBC). Methods: This population-based retrospective cohort study included adult non-Hispanic White (NHW) and Black (NHB) women diagnosed with unilateral DCIS between January 1990 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. County-level racialized economic segregation was measured using the Index of Concentration at the Extremes. Multilevel logistic regression and Cox proportional hazards regression accounting for county-level clustering were used to estimate the odds ratios (ORs) of local treatment, and hazard ratios (HRs) of subsequent IBC and mortality. Results: Of 103,898 cases, mean age was 59.5 years, 12.5% were NHB, 87.5% were NHW, 97.5% underwent surgery, 64.5% received radiotherapy following breast-conserving surgery, 7.1% developed IBC, and 18.6% died from all causes. Among women living in the least vs most privileged counties, we observed higher odds of receiving mastectomy (vs breast-conserving surgery) (OR=1.51, 95% CI 1.35-1.69; Ptrend&lt;0.001) and radiation therapy following breast-conserving surgery (OR=1.27, 95% CI 1.07-1.51; Ptrend&lt;0.01); the risk was higher in subsequent ipsilateral IBC (HR=1.16, 95% CI 1.02-1.32; Ptrend=0.04), not in breast cancer-specific mortality (HR=1.04, 95% CI 0.88-1.23; Ptrend=0.56). Conclusions: The results provide evidence for disparities in clinical treatment for DCIS and prognostic outcomes among women in racially and economically segregated counties. Impact: Our findings may inform geographically targeted multilevel interventions to reduce breast cancer burden and improve breast cancer care and equity.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1158/1055-9965.epi-24-0650
Kaitlyn M. Wojcik, Oliver W.A. Wilson, Meredith S. Shiels, Vanessa L. Sheppard, Jinani Jayasekera
Background: Cancer survivors show low physical activity participation rates in the U.S. However, there are limited national-level data on disparities in the prevalence of meeting physical activity guidelines among women with and without breast cancer. We aimed to evaluate national-level trends in meeting physical activity guidelines across demographic and socioeconomic characteristics of breast cancer survivors and women without cancer. Methods: Data for women aged ≥35-years with and without breast cancer were obtained from the 2004-2018 National Health Interview Survey (NHIS). We used NHIS survey weights to generate national-level prevalence estimates and calculate absolute and relative indices of disparity for breast cancer survivors and women without cancer meeting aerobic (150-mins/week) and muscle strengthening guidelines (2-sessions/week) stratified by demographic (e.g., race/ethnicity) and socioeconomic (e.g., homeownership) characteristics. Results: We included 5,845 breast cancer survivors and 160,162 women without cancer. The weighted percentage of breast cancer survivors meeting aerobic guidelines was 37.7% compared to 40.9% of women without cancer. Fewer women met muscle strengthening guidelines. There were lower proportions of women who were younger (<50-years), were non-Hispanic Black, were Hispanic, worked 35+ hours/week, or rented their home among breast cancer survivors meeting aerobic guidelines compared to women without cancer meeting aerobic guidelines. Conclusions: Breast cancer survivors were less likely to meet physical activity guidelines compared to women without cancer. Demographic and socioeconomic disparities may exist among breast cancer survivors and women without cancer meeting physical activity guidelines. Impact: Targeted interventions may be necessary to address low physical activity participation among breast cancer survivors.
{"title":"Racial, Ethnic, and Socioeconomic Disparities in Meeting Physical Activity Guidelines among Female Breast Cancer Survivors in the United States","authors":"Kaitlyn M. Wojcik, Oliver W.A. Wilson, Meredith S. Shiels, Vanessa L. Sheppard, Jinani Jayasekera","doi":"10.1158/1055-9965.epi-24-0650","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0650","url":null,"abstract":"Background: Cancer survivors show low physical activity participation rates in the U.S. However, there are limited national-level data on disparities in the prevalence of meeting physical activity guidelines among women with and without breast cancer. We aimed to evaluate national-level trends in meeting physical activity guidelines across demographic and socioeconomic characteristics of breast cancer survivors and women without cancer. Methods: Data for women aged ≥35-years with and without breast cancer were obtained from the 2004-2018 National Health Interview Survey (NHIS). We used NHIS survey weights to generate national-level prevalence estimates and calculate absolute and relative indices of disparity for breast cancer survivors and women without cancer meeting aerobic (150-mins/week) and muscle strengthening guidelines (2-sessions/week) stratified by demographic (e.g., race/ethnicity) and socioeconomic (e.g., homeownership) characteristics. Results: We included 5,845 breast cancer survivors and 160,162 women without cancer. The weighted percentage of breast cancer survivors meeting aerobic guidelines was 37.7% compared to 40.9% of women without cancer. Fewer women met muscle strengthening guidelines. There were lower proportions of women who were younger (&lt;50-years), were non-Hispanic Black, were Hispanic, worked 35+ hours/week, or rented their home among breast cancer survivors meeting aerobic guidelines compared to women without cancer meeting aerobic guidelines. Conclusions: Breast cancer survivors were less likely to meet physical activity guidelines compared to women without cancer. Demographic and socioeconomic disparities may exist among breast cancer survivors and women without cancer meeting physical activity guidelines. Impact: Targeted interventions may be necessary to address low physical activity participation among breast cancer survivors.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1158/1055-9965.epi-24-0263
Lanshan Huang, Sarah J. Winter, Linnea T. Olsson, Alina M. Hamilton, Sophia R. Halliday, Erin L. Kirk, Laura Farnan, Adrian Gerstel, Stephanie G. Craig, Stephen P. Finn, Melissa LaBonte Wilson, Suneil Jain, Melissa A. Troester, Eboneé N. Butler, Jeannette T. Bensen, Sara E. Wobker, Emma H. Allott
Background: Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood. Methods: We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy, and 101 radiation-treated prostate cancer patients in FASTMAN. Structured questionnaires administered in UNC CSC assessed physical activity. In both studies, digital image analysis of H&E-stained tissues was applied to quantify Tumor Infiltrating Lymphocytes (TILs) in segmented regions. Nanostring gene expression profiling in UNC CSC and microarray in FASTMAN were performed on tumor tissue and a 50-gene signature utilized to predict immune cell types. Results: Vigorous recreational activity, reported by 34 (29.1%) UNC men, was inversely associated with TILs abundance. Tumors of men reporting any vigorous activity versus none showed lower gene expression-predicted abundance of Th, exhausted CD4 T cells and macrophages. T cell subsets, including Treg, Th, Tfh, exhausted CD4 T cells, and macrophages were associated with increased risk of biochemical recurrence, only among men with ERG-positive tumors. Conclusions: Vigorous activity was associated with lower prostate tumor inflammation and immune microenvironment differences. Macrophages and T cell subsets, including those with immunosuppressive roles and those with lower abundance in men reporting vigorous exercise, were associated with worse outcomes in ERG-positive prostate cancer. Impact: Our novel findings contribute to our understanding of the role of the tumor immune microenvironment in prostate cancer progression, and may provide insight into how vigorous exercise could affect prostate tumor biology.
{"title":"Associations of prostate tumor immune landscape with vigorous physical activity and prostate cancer progression","authors":"Lanshan Huang, Sarah J. Winter, Linnea T. Olsson, Alina M. Hamilton, Sophia R. Halliday, Erin L. Kirk, Laura Farnan, Adrian Gerstel, Stephanie G. Craig, Stephen P. Finn, Melissa LaBonte Wilson, Suneil Jain, Melissa A. Troester, Eboneé N. Butler, Jeannette T. Bensen, Sara E. Wobker, Emma H. Allott","doi":"10.1158/1055-9965.epi-24-0263","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0263","url":null,"abstract":"Background: Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood. Methods: We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy, and 101 radiation-treated prostate cancer patients in FASTMAN. Structured questionnaires administered in UNC CSC assessed physical activity. In both studies, digital image analysis of H&E-stained tissues was applied to quantify Tumor Infiltrating Lymphocytes (TILs) in segmented regions. Nanostring gene expression profiling in UNC CSC and microarray in FASTMAN were performed on tumor tissue and a 50-gene signature utilized to predict immune cell types. Results: Vigorous recreational activity, reported by 34 (29.1%) UNC men, was inversely associated with TILs abundance. Tumors of men reporting any vigorous activity versus none showed lower gene expression-predicted abundance of Th, exhausted CD4 T cells and macrophages. T cell subsets, including Treg, Th, Tfh, exhausted CD4 T cells, and macrophages were associated with increased risk of biochemical recurrence, only among men with ERG-positive tumors. Conclusions: Vigorous activity was associated with lower prostate tumor inflammation and immune microenvironment differences. Macrophages and T cell subsets, including those with immunosuppressive roles and those with lower abundance in men reporting vigorous exercise, were associated with worse outcomes in ERG-positive prostate cancer. Impact: Our novel findings contribute to our understanding of the role of the tumor immune microenvironment in prostate cancer progression, and may provide insight into how vigorous exercise could affect prostate tumor biology.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1158/1055-9965.epi-24-0725
Abdi T. Gudina, Charles S. Kamen, Kelly A. Hirko, David H. Adler, Deborah J. Ossip, Edith M. Williams, Vinay K. Cheruvu, Ana-Paula Cupertino
Background: Scanning with low-dose computed tomography reduces lung cancer mortality by 20% among high-risk individuals. Despite its efficacy, the uptake of lung cancer screening (LCS) remains low. Our study aimed to estimate state-level and nationwide LCS rates among eligible individuals and to assess disparities in LCS uptake. Methods: Data for this study were obtained from the 2022 BRFSS. Multivariable logistic regression models were used to model the associations between predictors and outcome variables and to examine LCS variability across states. Results: Of the 28,071 participants eligible for LCS, 17.24% underwent LCS. Participants aged 65 -79 years were (OR: 1.75, 95%CI: 1.54 -1.99) more likely to undergo LCS than their younger counterparts. Those who were female (OR: 0.83, 95%CI: 0.73 - 0.94), divorced, separated, or widowed (OR: 0.85, 95%CI: 0.74-0.98), without health insurance (OR: 0.34, 95%CI: 0.22-0.53), without a primary care provider (OR: 0.29, 95%CI: 0.19-0.44), without COPD or those who did not disclose their COPD status ((OR: 0.35, 95%CI: 0.31-0.40) and (OR: 0.37, 95%CI: 0.19-0.73) respectively)) were less likely to undergo LCS than their respective counterparts. LCS uptake also varied significantly across U.S. states. Conclusions: We observed low uptake of LCS overall, and significant variability in LCS uptake by sociodemographic and health-related factors as well as by state of residence. Impact: The findings from this study have important implications for community health workers and healthcare clinicians and indicate the need to design effective interventions to increase LCS uptake targeting specific subgroups of populations and particular U.S. states.
{"title":"Lung Cancer Screening Uptake Under the Revised United States Preventive Service Task Force Guideline: Assessing Disparities","authors":"Abdi T. Gudina, Charles S. Kamen, Kelly A. Hirko, David H. Adler, Deborah J. Ossip, Edith M. Williams, Vinay K. Cheruvu, Ana-Paula Cupertino","doi":"10.1158/1055-9965.epi-24-0725","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0725","url":null,"abstract":"Background: Scanning with low-dose computed tomography reduces lung cancer mortality by 20% among high-risk individuals. Despite its efficacy, the uptake of lung cancer screening (LCS) remains low. Our study aimed to estimate state-level and nationwide LCS rates among eligible individuals and to assess disparities in LCS uptake. Methods: Data for this study were obtained from the 2022 BRFSS. Multivariable logistic regression models were used to model the associations between predictors and outcome variables and to examine LCS variability across states. Results: Of the 28,071 participants eligible for LCS, 17.24% underwent LCS. Participants aged 65 -79 years were (OR: 1.75, 95%CI: 1.54 -1.99) more likely to undergo LCS than their younger counterparts. Those who were female (OR: 0.83, 95%CI: 0.73 - 0.94), divorced, separated, or widowed (OR: 0.85, 95%CI: 0.74-0.98), without health insurance (OR: 0.34, 95%CI: 0.22-0.53), without a primary care provider (OR: 0.29, 95%CI: 0.19-0.44), without COPD or those who did not disclose their COPD status ((OR: 0.35, 95%CI: 0.31-0.40) and (OR: 0.37, 95%CI: 0.19-0.73) respectively)) were less likely to undergo LCS than their respective counterparts. LCS uptake also varied significantly across U.S. states. Conclusions: We observed low uptake of LCS overall, and significant variability in LCS uptake by sociodemographic and health-related factors as well as by state of residence. Impact: The findings from this study have important implications for community health workers and healthcare clinicians and indicate the need to design effective interventions to increase LCS uptake targeting specific subgroups of populations and particular U.S. states.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1158/1055-9965.epi-24-0478
Kamaria L. Lee, Varada Sarovar, Jennifer O. Lam, Wendy A. Leyden, Stacey E. Alexeeff, Alexandra N. Lea, Rulin C. Hechter, Haihong Hu, Julia L. Marcus, Qing Yuan, Jennifer R. Kramer, Lilie L. Lin, Elizabeth Y. Chiao, William J. Towner, Michael A. Horberg, Michael J. Silverberg
Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality for PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population. Methods: We identified 39,000 PWH and 387,767 demographically-matched PWoH in three integrated healthcare systems from 2000-2016. We estimated excess mortality for PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and Epstein-Barr virus (EBV)-related cancers; virus-unrelated cancers, and common individual cancers. We fitted a multivariable additive Poisson model to estimate excess mortality for PWH with cancer. Results: PWH with any cancer had excess mortality compared with PWoH (41.3/1000 person-years [py], 95% Confidence Interval [CI] 34.0, 48.7). The highest excess mortality was observed for EBV-related cancers (63.2/1000 py, 95% CI 47.8, 78.7), lung cancer (147.7/1000 py, 95% CI 41.1, 254.3) and non-Hodgkin lymphoma (70.5/1000 py, 95% CI 51.4, 89.6). Excess mortality for PWH was attenuated 2009-2016, and PWH with cancer had no excess mortality 5 years after diagnosis. Conclusions: PWH in care may have excess mortality from certain cancer types, although disparities may have attenuated over time and do not persist beyond 5 years after diagnosis. Impact: Findings may guide improved clinical practice, and suggest further research is needed to investigate whether cancer treatment or other factors contribute to mortality disparities for PWH with cancer.
背景：随着人类免疫缺陷病毒感染者（PWH）寿命的延长，包括癌症在内的慢性病负担也相应增加。我们的目标是估算与未感染艾滋病病毒的人群（PWoH）相比，感染癌症的 PWH 的超额死亡率，同时考虑到一般 PWH 群体中较高的背景死亡率。方法：2000-2016 年间，我们在三个综合医疗系统中识别了 39,000 名艾滋病感染者和 387,767 名人口匹配的艾滋病患者。我们估算了罹患癌症的威利人的超额死亡率，计算方法是威利人与威利人之间的癌症死亡率差异。我们评估了五类癌症：任何癌症；与病毒、人乳头瘤病毒和 Epstein-Barr 病毒 (EBV) 相关的癌症；与病毒无关的癌症以及常见的个体癌症。我们建立了一个多变量加性泊松模型来估算罹患癌症的威尔士人的超额死亡率。结果显示罹患任何癌症的公共卫生人员的死亡率均高于公共卫生人员（41.3/1000 人-年[py]，95% 置信区间[CI]34.0, 48.7）。EBV相关癌症（63.2/1000人年，95% CI 47.8，78.7）、肺癌（147.7/1000人年，95% CI 41.1，254.3）和非霍奇金淋巴瘤（70.5/1000人年，95% CI 51.4，89.6）的超额死亡率最高。2009-2016年，威尔士人的超额死亡率有所下降，患有癌症的威尔士人在确诊5年后没有超额死亡率。结论：接受护理的威利人可能会因某些癌症类型而导致超额死亡率，但随着时间的推移，差异可能会减小，并且在确诊后 5 年内不会持续存在。影响：研究结果可为改进临床实践提供指导，并表明需要进一步研究癌症治疗或其他因素是否会导致患有癌症的残疾人死亡率差异。
{"title":"Excess Mortality in Persons with Concurrent HIV and Cancer Diagnoses: A Retrospective Cohort Study","authors":"Kamaria L. Lee, Varada Sarovar, Jennifer O. Lam, Wendy A. Leyden, Stacey E. Alexeeff, Alexandra N. Lea, Rulin C. Hechter, Haihong Hu, Julia L. Marcus, Qing Yuan, Jennifer R. Kramer, Lilie L. Lin, Elizabeth Y. Chiao, William J. Towner, Michael A. Horberg, Michael J. Silverberg","doi":"10.1158/1055-9965.epi-24-0478","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0478","url":null,"abstract":"Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality for PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population. Methods: We identified 39,000 PWH and 387,767 demographically-matched PWoH in three integrated healthcare systems from 2000-2016. We estimated excess mortality for PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and Epstein-Barr virus (EBV)-related cancers; virus-unrelated cancers, and common individual cancers. We fitted a multivariable additive Poisson model to estimate excess mortality for PWH with cancer. Results: PWH with any cancer had excess mortality compared with PWoH (41.3/1000 person-years [py], 95% Confidence Interval [CI] 34.0, 48.7). The highest excess mortality was observed for EBV-related cancers (63.2/1000 py, 95% CI 47.8, 78.7), lung cancer (147.7/1000 py, 95% CI 41.1, 254.3) and non-Hodgkin lymphoma (70.5/1000 py, 95% CI 51.4, 89.6). Excess mortality for PWH was attenuated 2009-2016, and PWH with cancer had no excess mortality 5 years after diagnosis. Conclusions: PWH in care may have excess mortality from certain cancer types, although disparities may have attenuated over time and do not persist beyond 5 years after diagnosis. Impact: Findings may guide improved clinical practice, and suggest further research is needed to investigate whether cancer treatment or other factors contribute to mortality disparities for PWH with cancer.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1158/1055-9965.epi-24-0450
Joseph Boyle, Jessica Yau, Jimmie L. Slade, Derrick A. Butts, Jessica Wimbush, Jong Y. Park, Arif Hussain, Eberechukwu Onukwugha, Cheryl L. Knott, David C. Wheeler, Kathryn Hughes Barry
Background: Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race. Methods: We evaluated associations between aggressive prostate cancer and four ND metrics—Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004–2021). Results: We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00–1.30; RI, OR = 1.27, CI, 1.07–1.51; redlining, OR = 1.77; CI, 1.23–2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13–1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men. Conclusions: We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race. Impact: Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities.
{"title":"Neighborhood Disadvantage and Prostate Tumor Aggressiveness among African American and European American Men","authors":"Joseph Boyle, Jessica Yau, Jimmie L. Slade, Derrick A. Butts, Jessica Wimbush, Jong Y. Park, Arif Hussain, Eberechukwu Onukwugha, Cheryl L. Knott, David C. Wheeler, Kathryn Hughes Barry","doi":"10.1158/1055-9965.epi-24-0450","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0450","url":null,"abstract":"Background: Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race. Methods: We evaluated associations between aggressive prostate cancer and four ND metrics—Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004–2021). Results: We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00–1.30; RI, OR = 1.27, CI, 1.07–1.51; redlining, OR = 1.77; CI, 1.23–2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13–1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men. Conclusions: We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race. Impact: Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1158/1055-9965.epi-24-0594
Sarah S. Kalia, Nicholas J. Boddicker, Siddhartha Yadav, Hongyan Huang, Jie Na, Chunling Hu, Christine B. Ambrosone, Song Yao, Christopher A. Haiman, Fei Chen, Esther M. John, Allison W. Kurian, Boya Guo, Sara Lindström, Paul Auer, James V. Lacey, Susan L. Neuhausen, Maria Elena. Martinez, Dale P. Sandler, Katie M. O'Brien, Jack A. Taylor, Lauren R. Teras, James M. Hodge, Adriana Lori, Clara Bodelon, Amy Trentham-Dietz, Elizabeth S. Burnside, Celine M. Vachon, Stacey J. Winham, David E. Goldgar, Susan M. Domchek, Katherine L. Nathanson, Jeffrey N. Weitzel, Fergus J. Couch, Peter Kraft
Background: Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited. Methods: We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case-control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium. Results: The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had >20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (<20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population. Conclusions: These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification. Impact: Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts.
{"title":"Development of a breast cancer risk prediction model integrating monogenic, polygenic, and epidemiologic risk","authors":"Sarah S. Kalia, Nicholas J. Boddicker, Siddhartha Yadav, Hongyan Huang, Jie Na, Chunling Hu, Christine B. Ambrosone, Song Yao, Christopher A. Haiman, Fei Chen, Esther M. John, Allison W. Kurian, Boya Guo, Sara Lindström, Paul Auer, James V. Lacey, Susan L. Neuhausen, Maria Elena. Martinez, Dale P. Sandler, Katie M. O'Brien, Jack A. Taylor, Lauren R. Teras, James M. Hodge, Adriana Lori, Clara Bodelon, Amy Trentham-Dietz, Elizabeth S. Burnside, Celine M. Vachon, Stacey J. Winham, David E. Goldgar, Susan M. Domchek, Katherine L. Nathanson, Jeffrey N. Weitzel, Fergus J. Couch, Peter Kraft","doi":"10.1158/1055-9965.epi-24-0594","DOIUrl":"https://doi.org/10.1158/1055-9965.epi-24-0594","url":null,"abstract":"Background: Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited. Methods: We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case-control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium. Results: The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had &gt;20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (&lt;20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population. Conclusions: These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification. Impact: Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts.","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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