Body Size, Physical Activity and Breast Cancer Subtypes

非洲血统的美国妇女（AA）受侵袭性更强的乳腺癌的影响， 欧洲血统的女性（EA）。越来越多的证据表明，乳腺癌的亚型 有不同的病因，有提示性的流行病学数据的关系，身体大小和 身体活动与乳腺癌亚型的发病率（例如，腰臀比与 基底细胞样癌）。AA女性比EA女性更经常肥胖和久坐，差异可能 导致了乳腺癌的差异。我们将评估身体大小和 通过汇集来自四项大型研究的数据和DNA样本， AA妇女的乳腺癌：黑人妇女健康研究，卡罗莱纳乳腺癌研究， 妇女健康研究圈和多民族队列。我们建议评估身体大小的措施， 包括18岁时的总体肥胖、腹部肥胖和体重指数，以及身体指标。 在生命周期的不同时间，与乳腺癌亚型的发病率有关，包括ER- /PR-、五种内在亚型和早发性乳腺癌。根据研究对象的DNA，我们将基因分型 胰岛素和IGF-1通路中的SNP，评估其与乳腺癌亚型的关联， 然后评估身体大小和身体活动与遗传变异对风险的联合影响， 亚型特别令人感兴趣的假设是，高WHR与ER发生率增加相关， /PR-和基底细胞样癌，高体重指数伴绝经前管腔A发生率降低 癌症和体力活动，特别是在生育早期，ER-/PR-和 基底细胞样癌在交叉项目目标中，我们将评估遗传变异的修饰效果 与乳腺癌相关的类固醇激素途径中的项目2和炎症中的项目4 身体大小和体力活动与乳腺癌亚型之间的关系。本研究 强大的力量来实现所提出的目标。这项研究将大大增加对 侵袭性乳腺癌的病因学。特别重要的是，要确定非政府组织协会的性质， 体型和体力活动与乳腺癌的风险有关，因为这些因素是可以改变的。

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.