Life Course Cancer Epidemiology Cohort in Women

我们建议继续跟进护士健康研究II(NHSII)，这是一个癌症流行病学队列 调查了116,430名年龄在25岁到42岁之间的女性。NHSII在许多方面都是一个独特的群体，因为 只有一大批女性在绝经前登记，并有近30年的反复测量 曝光。我们有关于吸烟、体重、用药、饮食、体力活动和医疗方面的信息 诊断每两到四年更新一次。此外，我们还收集了有关子宫内和婴儿的详细数据 暴露(来自参与者的母亲)、高中期间的饮食和其他独特的暴露信息。我们 使用国家死亡指数和其他方法几乎完全确定了死亡人数。以下是- NHSII队列的UP仍然很高，累积随访率为94%。NHSII生物仓库包括血浆， 来自29,611名女性的红细胞、白细胞和第一次晨尿样本；其中三分之二 妇女提供了绝经前的定时卵泡和黄体样本。从2008年到2011年，16510名女性 在大多数人绝经后提供第二次血液和尿液样本。我们也有面颊细胞 另外29,859名女性的DNA。除了这些资源，我们最近还获得了收集粪便的资金 来自25,000名参与者的样本用于微生物组分析。我们已经收集了档案组织块用于 发生乳腺癌和卵巢癌以及黑色素瘤(大约70%的请求已经获得)；以及 其他癌症的收集工作正在进行中。乳腺癌和卵巢癌组织已经被用来检测基因 组织芯片被广泛用于免疫组织化学。诊断前 已经收集了乳腺癌病例和对照的乳房X光照片，以及来自 先前的良性病变活检。队列中有相当大比例的人有GWA和代谢组学数据 来自嵌套病例对照分析。这个队列很有成效；已经有330多篇论文 在过去五年里出版的，而且出版的速度越来越快。利用我们的现役资源 共享部分，我们作为NCI Cohort财团的成员参与了19个财团，NCI Cohort财团是 为数不多的对绝经前妇女提供大量数据的队列，也是 绝经前乳腺癌。我们还与外部个人进行了积极的数据共享协作 调查人员。这些外部合作和财团在2012年期间出版了63多份出版物 目前的资助期。在目前的提案中，我们的目标是继续进行队列后续行动，并保持这些 独特的资源。我们将继续采集乳腺癌患者的血液和尿液样本 还提供了诊断前样本、发生癌症的肿瘤组织以及诊断前和 绝经后乳房X光检查。我们建议对肠道进行一项长期(2-3年)可重复性研究。 微生物组。最后，我们将加强数据管理和分析工具，以最大限度地提高效率和利用率 利用我们的复杂资源来确定癌症发病率和存活率的可改变的决定因素。

We propose to continue the follow-up of the Nurses' Health Study II (NHSII), a Cancer Epidemiology Cohort of 116,430 women enrolled at ages 25 to 42 years in 1989. The NHSII is a unique cohort in many ways, as the only large cohort of women enrolled before menopause and with nearly 30 years of repeated measures of exposures. We have information on smoking, weight, medication use, diet, physical activity and medical diagnoses updated every two to four years. Further, we have collected detailed data on in utero and infant exposures (from participants' mothers), diet during high school, and other unique exposure information. We have nearly complete ascertainment of deaths using the National Death Index and other methods. The follow- up of the NHSII cohort remains high, with 94% cumulative follow-up. The NHSII biorepository includes plasma, red blood cells, white blood cells, and first morning urine samples from 29,611 women; two thirds of these women contributed timed follicular and luteal premenopausal samples. In 2008 to 2011, 16,510 women provided second blood and urine samples when the majority were postmenopausal. We also have cheek cell DNA from an additional 29,859 women. Adding to these resources, we were recently funded to collect fecal samples from 25,000 participants for microbiome analysis. We have collected archival tissue blocks for incident breast and ovarian cancers and melanoma (approximately 70% of requests have been obtained), and collections for other cancers are ongoing. Breast and ovarian cancer tissues have been utilized for gene expression, and tissue microarrays are used extensively for immunohistochemistry. Prediagnostic mammograms have been collected for breast cancer cases and controls, as well as pathology material from previous biopsies of benign lesions. Substantial proportions of the cohort have GWAS and metabolomic data from nested case-control analyses. This cohort has been highly productive; over 330 papers have been published during the last five years, and the rate of publication is increasingly rapidly. With our active resource sharing component, we have participated in 19 consortia as a member of the NCI Cohort Consortium, one of the few cohorts contributing substantial data on premenopausal women and the largest contributor of premenopausal breast cancers. We also have active data sharing collaborations with individual external investigators. These external collaborations and consortia have resulted in more than 63 publications during the current funding period. In the current proposal, we aim to continue cohort follow-up and maintain these unique resources. We will continue collecting blood and urine samples from women with breast cancer who also provided prediagnostic samples, tumor tissue for incident cancers, and pre-diagnostic pre- and postmenopausal mammograms. We propose to conduct a long-term (2-3 year) reproducibility study for gut microbiome. Finally, we will enhance our data management and analytic tools to maximize efficiency and use of our complex resources to identify modifiable determinants of cancer incidence and survival.