Life Course Cancer Epidemiology Cohort in Women

我们建议继续进行护士健康研究II（NHSII）的随访，这是一项癌症流行病学队列研究， 1989年有116 430名25至42岁的妇女入学。NHSII在许多方面都是一个独特的群体， 只有一个大的妇女队列在绝经前登记，并有近30年的重复测量， 暴露。我们有关于吸烟、体重、药物使用、饮食、体育活动和医疗的信息 诊断每2 - 4年更新一次。此外，我们还收集了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队列的随访率仍然很高，累积随访率为94%。NHSII生物储存库包括血浆， 红细胞、白色细胞和第一次晨尿样本，来自29，611名妇女;其中三分之二的人 妇女提供定时卵泡和黄体绝经前样品。2008年至2011年，16 510名妇女 提供了第二次血液和尿液样本时，大多数是绝经后。我们还有颊细胞 另外29,859名女性的DNA。除了这些资源，我们最近还得到资助， 从25，000名参与者中提取样本进行微生物组分析。我们收集了档案组织块， 乳腺癌、卵巢癌和黑色素瘤（约70%的申请已获得）， 其他癌症的收集工作正在进行中。乳腺癌和卵巢癌组织已被用于基因转移。 组织表达和组织微阵列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组的乳房X线照片，以及来自 以前的良性病变活检。相当比例的队列具有GWAS和代谢组学数据 巢式病例对照分析。这一群体的生产力很高;已经发表了330多篇论文。 在过去的五年里，出版的速度越来越快。利用我们的资源 作为NCI队列联盟的成员，我们参加了19个联盟， 少数几个队列提供了绝经前妇女的大量数据， 绝经前乳腺癌我们还与外部的个人进行积极的数据共享合作， investigators.这些外部合作和联盟导致超过63个出版物， 目前的融资期。在目前的提案中，我们的目标是继续队列随访，并保持这些 独特的资源。我们将继续收集患有乳腺癌的妇女的血液和尿液样本， 还提供了诊断前样本，肿瘤组织的事件癌症，和诊断前的前， 绝经后的乳房X光片我们建议对肠道进行长期（2-3年）重现性研究 微生物组最后，我们将增强数据管理和分析工具，以最大限度地提高效率和利用率 我们复杂的资源来确定癌症发病率和生存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.