Cohort Study of Genetic Susceptibility to Breast Cancer

描述（由申请人提供）：我们建议研究 乳腺癌候选基因中常见的潜在低多态性 三个前瞻性队列中的癌症;护士健康研究I和II， 女性健康研究。特定的假说与基因变异有关 对类固醇激素代谢很重要（性激素结合球蛋白， 和孕激素受体）与乳腺癌风险的关系， 绝经后激素使用与乳腺癌关系的修正 基因型我们还将研究两个基因的多态性，这两个基因与细胞凋亡有关。 周期控制（HER 2原癌基因，I型TGF β受体）， 在其他研究中与乳腺癌风险相关。最后，我们将寻求 复制我们在当前资助周期中观察到的 在年轻时开始吸烟和CYP 1A 1基因的变异， 乳腺癌的程度家族史和更长的（CAG）n重复在 雄激素受体我们估计， 护士健康研究I中的261例，护士健康研究II中的1050例 妇女健康研究中的案例。在这2851起事故中， 将有> 90%的能力检测1.5或更大的相对风险， 大多数感兴趣的基因型的主效应。我们也将有 检测这些基因型之间相互作用的能力， 乳腺癌的危险因素。

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.