HORMONES, DIET AND RISK OF OVARIAN CANCER

描述(申请人提供)：我们建议对激素进行详细的分析， 使用从护士健康研究中收集的数据研究卵巢癌的饮食和遗传危险因素 (NHS)自1976年以来，从护士健康研究II(NHSII)自1989年以来。我们预计有857个种姓 NHS中的163例和NHSII中的163例将在2006年的后续周期中得到确认；大约25% (n~250)为绝经前。具体地说，我们建议评估早期的体型(在 5岁和10岁)，18岁时的身体质量指数，成年人的腰臀比，身高，体力活动和 不活动、出生体重、膳食叶酸和相关营养素，以及止痛/消炎药物 与卵巢癌风险有关的药物。此外，我们将确定出生体重、腰围到臀围 比例和止痛药的使用与性激素有关，如雌二醇和 孕激素。此外，使用嵌套病例对照设计，我们将检查血浆的关系 血清肌酸蛋白、白介素6和肿瘤坏死因子-α受体2与卵巢癌的关系 收集自1989-1990年的32,826名NHS参与者和1996-1998年的26,616名NHSII参与者。 我们承诺，使用来自黄褐色毛皮、口腔细胞样本或非肿瘤组织的生殖系DNA 评估卵巢癌风险与亚甲基四氢叶酸基因多态性的关系 还原酶(MTHFR)基因(667C&gt；T)。我们已经建立了一个来自患有癌症的妇女的肿瘤组织库 突发卵巢癌。利用这一资源，我们建议检查异常甲基化 卵巢肿瘤内的某些基因，并评估这些异常是否与 叶酸及其他相关营养素的膳食摄入量。对于某些暴露，这样的体力活动和 体重指数，我们将能够比以前更详细地检查与卵巢癌的关系 研究；对于其他暴露，如炎症标志物，我们将是第一个前瞻性研究。一个 此应用程序的主要优势是我们能够前瞻性地检查这些因素以及可用性 在超过25年的调查问卷数据中，存档的血浆和DNA样本以及肿瘤组织 卵巢癌病例的样本。最后，该项目不仅将提高我们对 疾病病因，但也可能具有重要的公共卫生影响，因为这些风险中的几个 因素是可以修改的。

DESCRIPTION (provided by applicant): We propose to conduct detailed analyses of hormone, dietary, and genetic risk factors of ovarian cancer using data collected from the Nurses' Health study (NHS) since 1976 and from the Nurses' Health study II (NHSII) since 1989. We expect that 857 castes in NHS and 163 cases in NHSII will be confirmed by the 2006 follow-up cycle; approximately 25 percent (n~250) of all cases will be pre-menopausal. Specifically we propose to evaluate early body shape (at ages 5 and 10), body mass index at age 18, adult waist-to-hip ratio, height, physical activity and inactivity, birthweight, dietary folate and related nutrients, and analgesic/anti-inflammatory medication used in relation to ovarian cancer risk. In addition, we will determine whether birthweight, waist-to-hip ratio, and analgestic medication use are associated with sex hormones such as estradiol and progesterone. Further, using a nested case-control design, we will examine relationships of plasma creactine protein, interleukin-6, and TNF-alpha receptor 2 with ovarian cancer using blood samples collected from 32,826 NHS participants in 1989-1990 and 26,616 NHSII Participants in 1996-1998. Using germline DNA from archived buffy coat, buccal cell specimens, or non-tumor tissue, we promise to evaluate ovarian cancer risk in relation to genetic polymorphisms in the methlyene tetrahydrofolate reductase (MTHFR) gene (667 C>T). We have established a bank of tumor tissue from women with incident ovarian cancer. Using this resource we propose to examine the aberrant methalyation of certain genes within ovarian tumors and to assess whether these aberrations are associated with dietary intake of folate and other related nutrients. For some exposures, such a physical activity and body mass index, we will be able to examine relations to ovarian cancer in greater detail than previous studies; for other exposures, such as inflammatory markers, ours will be the first prospective study. A major strength of this application is our ability to examine these factors prospectively and the availability of over 25 years worth of questionnaire data, archived plasma and DNA samples and tumor tissue samples from ovarian cancer cases. Finally the project will not only improve our understanding of disease etiology, but also could have important public health implications because several of these risk factors are modifiable.