Cohort Study of Genetic Susceptibility to Breast Cancer

描述(由申请人提供)：我们建议研究以下关系 乳腺癌候选基因中常见的潜在低外显性多态 三个前瞻性队列中的癌症；护士健康研究I和II，以及 女性健康研究。特定的假说与基因的变异有关 对类固醇激素代谢很重要(性激素结合球蛋白，CYP 19 和黄体酮受体)与乳腺癌的风险，以及影响 绝经后激素使用与乳腺癌关系的研究进展 按基因分型。我们还将检查与细胞有关的两个基因的多态。 周期控制(HER2原癌基因，转化生长因子β受体I型) 在其他研究中与乳腺癌风险有关。最后，我们将寻求 为了复制我们在当前赠款周期中观察到的相互作用 在年轻时开始吸烟和CYP1A1基因的变异，以及第一 乳腺癌的学位家族史和较长的(CAG)n重复 雄激素受体。我们估计到2019年，我们将有1540例乳腺癌病例。 《护士健康研究I》261例，《护士健康研究II》1050例 妇女健康研究中的案例。在这2851宗事故个案中，我们 将拥有90%的权力来检测1.5或更高的 大多数感兴趣的基因型主效应。我们还将拥有 检测这些基因类型之间相互作用的强大力量 已确定的乳腺癌危险因素。

DESCRIPTION (provided by applicant): We propose to study the relations between common potentially low-penetrance polymorphisms in candidate genes for breast cancer in three prospective cohorts; the Nurses' Health Studies I and II, and the Women's Health Study. Specific hypotheses relate variants in genes important to steroid hormone metabolism (sex-hormone binding globulin, CYP 19 and the progesterone receptor) with risk of breast cancer, and effect modification of the relation of postmenopausal hormone use with breast cancer by genotype. We will also examine polymorphisms in two genes involved in cell cycle control (the HER2 proto-oncogene, the TGFbeta receptor type I) that have been associated with breast cancer risk in other studies. Finally, we will seek to replicate interactions we observed in the current grant cycle between initiation of smoking at a young age and variants in the CYP1A1 gene, and first degree family history of breast cancer and longer (CAG)n repeats in the androgen receptor. We estimate we will accrue 1540 cases of breast cancer in the Nurses' Health Study I, 261 cases in the Nurses' Health Study II, and 1050 cases in the Women's Health Study. With this total of 2851 incident cases, we will have >90 percent power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and established breast cancer risk factors.