American women of African ancestry (AA) are affected with more aggressive breast cancers and at younger ages than women of European ancestry (EA). Increasing evidence indicates that subtypes of breast cancer have different etiologies, and there are suggestive epidemiologic data regarding the relation of body size and physical activity to incidence of breast cancer subtypes (e.g., positive association of waist-hip ratio with basal-like cancer). AA women are more often obese and sedentary than EA women, differences that could be contributing to the observed breast cancer disparities. We will assess associations of body size and physical activity with subtypes of breast cancer by pooling data and DNA samples from four large studies of breast cancer in AA women: the Black Women's Health Study, the Carolina Breast Cancer Study, the Women's Circle of Health Study, and the Multi-ethnic Cohort. We propose to assess measures of body size, including overall obesity, abdominal obesity, and body mass index at age 18, and measures of physical activity at different times during the lifespan, in relation to incidence of breast cancer subtypes, including ER- /PR-, five intrinsic subtypes, and early onset breast cancer. Based on study subjects'DNA, we will genotype SNPs in the insulin and IGF-1 pathways, assess their association with the subtypes of breast cancer, and then assess the joint effects of body size and physical activity with the genetic variants on risk of the subtypes. Hypotheses of particular interest are that high WHR is associated with increased incidence of ER- /PR- and basal-like cancer, high body mass index with decreased incidence of premenopausal luminal A cancer, and physical activity, particularly in early reproductive years, with decreased incidence of ER-/PR- and basal-like cancer. In cross project aims, we will assess the modifying effects of genetic variants associated with breast cancer in Project 2 in the steroid hormone pathway and Project 4 in the inflammation pathway on the associations of body size and physical activity with breast cancer subtypes. This study has excellent power to achieve the proposed aims. The study will add appreciably to understanding of the etiology of aggressive breast cancers. It is particularly important to establish the nature of the associations of body size and physical activity with risk of breast cancer because these factors are modifiable.

Public Health Relevance

African American women are affected by more aggressive forms of breast cancer than women of European ancestry. At the same time, larger proportions of African American women are obese and lower proportions participate in exercise. The proposed project will provide information on how obesity and exercise, together with genetic makeup, are associated with subtypes of breast cancer, including those that are most aggressive. Because obesity and exercise are modifiable, the information obtained could lead to interventions that decrease these breast cancer disparities.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Roswell Park Cancer Institute Corp
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Bertrand, Kimberly A; Gerlovin, Hanna; Bethea, Traci N et al. (2017) Pubertal growth and adult height in relation to breast cancer risk in African American women. Int J Cancer 141:2462-2470
Espinal, Allyson C; Buas, Matthew F; Wang, Dan et al. (2017) FOXA1 hypermethylation: link between parity and ER-negative breast cancer in African American women? Breast Cancer Res Treat 166:559-568
Charlot, Marjory; Castro-Webb, Nelsy; Bethea, Traci N et al. (2017) Diabetes and breast cancer mortality in Black women. Cancer Causes Control 28:61-67
Roberts, Michelle R; Sucheston-Campbell, Lara E; Zirpoli, Gary R et al. (2017) Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry. Mol Carcinog 56:1000-1009
Khoury, Thaer; Zirpoli, Gary; Cohen, Stephanie M et al. (2017) Ki-67 Expression in Breast Cancer Tissue Microarrays: Assessing Tumor Heterogeneity, Concordance With Full Section, and Scoring Methods. Am J Clin Pathol 148:108-118
Feng, Ye; Rhie, Suhn Kyong; Huo, Dezheng et al. (2017) Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry. Cancer Epidemiol Biomarkers Prev 26:1016-1026
Bertrand, Kimberly A; Bethea, Traci N; Adams-Campbell, Lucile L et al. (2017) Differential Patterns of Risk Factors for Early-Onset Breast Cancer by ER Status in African American Women. Cancer Epidemiol Biomarkers Prev 26:270-277
Williams, Lindsay A; Olshan, Andrew F; Hong, Chi-Chen et al. (2017) Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium. Cancer Epidemiol Biomarkers Prev 26:787-794
Allott, Emma H; Cohen, Stephanie M; Geradts, Joseph et al. (2016) Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium. Cancer Epidemiol Biomarkers Prev 25:470-8
Yao, Song; Haddad, Stephen A; Hu, Qiang et al. (2016) Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium. Int J Cancer 138:2118-26

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