Premenopausal Hormone Levels and Risk of Breast Cancer

描述（由申请人提供）：乳腺癌的流行病学表明 绝经前激素的主要病因作用，但目前的数据没有 指出哪些特定的激素是最重要的，在什么水平 风险增加。我们建议分析从 29，613名参与护士健康研究II（NHSII）的参与者提供了样本 1996-99年，收集时年龄为32至53岁。其中19,092人 根据妇女的月经周期对样品进行计时;对于这些妇女， 可获得早期卵泡和黄体中期血液样本。样品 已储存在-130摄氏度或更低的液氮中 自收藏以来，我们会检测那些被诊断为 在血液采集后与乳腺癌患者进行比较， 无病（即，嵌套病例对照设计），从而有效地利用 这些前瞻性收集的样本。 具体来说，我们将研究乳腺癌发病率与 和（1）卵泡中雌激素、雄激素和催乳素的血浆水平 和黄体期的月经周期，（2）血浆胰岛素样 生长因子I（IGF-I）、IGF结合蛋白-3（IGFBP-3）、IGFBP-1和游离 IGF-I，（3）IGF-I和IGFBP-3基因多态性，（4）血浆水平 胰岛素和C肽的多态性，以及（5）胰岛素受体的多态性 底物I（IRS-i）基因。 正在进行的NHSII队列（CA 50385）将提供队列随访， 除了提供信息外，还记录乳腺癌诊断 重要的协变量（如体重指数，产次，初潮年龄， 酒精摄入量和乳腺癌家族史）。 总体而言，队列的大规模，前瞻性设计，高 随访率、详细的暴露数据和存档的可用性 血液样本（在月经周期内收集）提供了一个 这是一个独特的机会，可以检验几个关于公共卫生重要性的假设。

DESCRIPTION (provided by applicant): The epidemiology of breast cancer suggests a central etiologic role for premenopausal hormones, yet current data do not indicate which specific hormones are of greatest importance and at what levels risk is increased. We propose to analyze blood samples collected from the 29,613 participants in the Nurses' Health Study II (NHSII) who provided samples in 1996-99 and were 32 to 53 years of age at collection. 19,092 of these samples were timed according to the woman's menstrual cycle; for these women, both early follicular and midluteal blood samples are available. The samples have been stored at -130 degrees Centigrade or colder in liquid nitrogen freezers since collection. We will assay samples from women who were diagnosed with breast cancer after blood collection and matched controls who remained disease-free (i.e., a nested case-control design), thus efficiently utilizing these prospectively collected samples. Specifically, we will examine the relationships between breast cancer incidence and (1) plasma levels of estrogens, androgens and prolactin in the follicular and luteal phases of the menstrual cycle, (2) plasma levels of insulin-like growth factor I (IGF-I), IGF binding protein-3 (IGFBP-3), IGFBP-1 and free IGF-I, (3) polymorphisms in both the IGF-l and IGFBP-3 genes, (4) plasma levels of insulin and c-peptide, and (5) a polymorphism in the insulin receptor substrate I (IRS-i) gene. The ongoing NHSII cohort (CA50385) will provide follow-up of the cohort and documentation of breast cancer diagnoses in addition to providing information on important covariates (such as body mass index, parity, age at menarche, alcohol intake and family history of breast cancer) for the proposed study. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed exposure data, and the availability of archived blood specimens (with collection timed within the menstrual cycle) provide a unique opportunity to test several hypotheses of public health importance.