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)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Roswell Park Cancer Institute Corp
United States
Zip Code
Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara; Bensen, Jeannette T et al. (2016) Admixture Mapping of African-American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes. Front Genet 7:170
Bethea, Traci N; Rosenberg, Lynn; Castro-Webb, Nelsy et al. (2016) Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women. Cancer Epidemiol Biomarkers Prev 25:366-73
Ruiz-Narváez, Edward A; Haddad, Stephen A; Lunetta, Kathryn L et al. (2016) Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium. Breast Cancer Res Treat 155:355-63
Palmer, Julie R; Gerlovin, Hanna; Bethea, Traci N et al. (2016) Predicted 25-hydroxyvitamin D in relation to incidence of breast cancer in a large cohort of African American women. Breast Cancer Res 18:86
Bertrand, Kimberly A; Bethea, Traci N; Adams-Campbell, Lucile L et al. (2016) Differential patterns of risk factors for early-onset breast cancer by ER status in African American women. Cancer Epidemiol Biomarkers Prev :
Rosenberg, Lynn; Bethea, Traci N; Viscidi, Emma et al. (2016) Postmenopausal Female Hormone Use and Estrogen Receptor-Positive and -Negative Breast Cancer in African American Women. J Natl Cancer Inst 108:
Chollet-Hinton, Lynn; Anders, Carey K; Tse, Chiu-Kit et al. (2016) Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case-control study. Breast Cancer Res 18:79
Allott, Emma H; Geradts, Joseph; Sun, Xuezheng et al. (2016) Intratumoral heterogeneity as a source of discordance in breast cancer biomarker classification. Breast Cancer Res 18:68
Cheng, Ting-Yuan David; Ambrosone, Christine B; Hong, Chi-Chen et al. (2016) Genetic variants in the mTOR pathway and breast cancer risk in African American women. Carcinogenesis 37:49-55
Cheng, Ting-Yuan David; Shankar, Jyoti; Zirpoli, Gary et al. (2016) Genetic variants in the mTOR pathway and interaction with body size and weight gain on breast cancer risk in African-American and European American women. Cancer Causes Control 27:965-76

Showing the most recent 10 out of 42 publications