Women's Health Study: Infrastructure support for cohort follow-up

本提案仅寻求对核心职能的基础设施支持，以便对 妇女健康研究（WHS），PAR-17-233。WHS始于1992年，是一项随机试验， 阿司匹林、β-胡萝卜素和维生素E用于预防癌症和心血管疾病（CVD）， 45岁以上的健康女性在随机化之前，28，345名女性（71%）提供了血液样本：所有人都有 已对广泛的生物标志物进行了分析;全基因组关联研究（GWAS）已被 完成>25,000，外显子组芯片基因分型> 22000。试验于2004年结束，33,682人（或89%） 愿意接受观察性跟踪妇女通过年度问卷报告， 广泛的暴露和终点;我们通过医学检查证实了自我报告的癌症和CVD终点 记录，以及医疗记录和/或死亡证明的死亡原因。器械评估的7天体格检查 对17,708名妇女的活动和久坐行为进行了调查。WHS的独特之处在于， 基因数据以及客观评估的身体活动和久坐行为。 随访非常好：近24年后，发病率随访仍为89.6%，死亡率随访为 几乎百分之百由于在世参与者的平均年龄为77.1岁，事件发生率大幅增加： 在目前的资助结束时（2019年8月31日），将有7,769例确诊的癌症;到拟议的 在资助周期（2024年8月31日），将确认10 869例癌症。这将大大提高WHS的能力， 解决重要的癌症问题，包括特定部位癌症，罕见癌症和肿瘤的检查- 具体特点。WHS积极与内部和外部研究人员共享数据， 发表了650篇论文，使用WHS数据获得了106项赠款，并在22个NCI队列联盟中进行了合作 项目目前，没有一项辅助研究为癌症的确定和验证提供资金 (and CVD）终点。 在建议的拨款期内，我们会继续进行卫生署卫生处的基础设施，包括跟进和评估工作 自我报告的暴露和终点，以及WHS生物标本库的维护，以进一步 促进数据共享和协作。WHS还致力于继续在研究方面发挥领导作用 与基于基因的疾病预测和基因-环境相互作用相关的目标;改进 评估身体活动和久坐行为，以研究与健康结果的关联，以及 低剂量阿司匹林的长期化学保护作用的评价。未来将寻求独立资金 在此期间，我们将讨论这些领域的具体假设。未来5年，持续的基础设施支持和 随访对于最大限度地利用这一有价值的大规模癌症妇女队列的成本效益至关重要 拥有丰富的已经收集的表型和遗传数据资源，特别是因为许多WHS发现 已经并可以直接转化为临床和公共卫生实践或正式建议。

This proposal seeks infrastructure support only for core functions to conduct 5 years of continued follow-up of the Women's Health Study (WHS), under PAR-17-233. The WHS began in 1992 as a randomized trial testing aspirin, beta-carotene, and vitamin E for prevention of cancer and cardiovascular disease (CVD) in 39,876 healthy women over age 45. Prior to randomization, 28,345 women (71%) provided a blood sample: all have been assayed for a wide range of biomarkers; genome-wide association studies (GWAS) have been completed on >25,000, and exome chip genotyping on >22,000. The trial ended in 2004, and 33,682 (or 89% of surviving women were willing to be followed observationally. Women report via yearly questionnaires on a wide range of exposures and endpoints; we confirm self-reported cancer and CVD endpoints with medical records, and cause of death by medical records and/or death certificates. Device-assessed 7-day physical activity and sedentary behavior has been collected on 17,708 women. The WHS is unique in having extensive genetic data as well as objectively-assessed physical activity and sedentary behavior in such a large cohort. Follow-up is excellent: after almost 24 years, morbidity follow-up is still 89.6%% and mortality follow-up is virtually 100%. As the average age of living participants is 77.1 years, event rates are increasing substantially: at the end of current funding (8/31/19), 7,769 confirmed cancers will have occurred; by the end of the proposed funding cycle (8/31/24), 10,869 cancers will be confirmed. This will substantially increase WHS's ability to address important cancer questions, including examination of site-specific cancers, rare cancers, and tumor- specific characteristics. The WHS has actively shared data with internal and external researchers, resulting in 650 papers published, 106 funded grants using WHS data, and collaboration in 22 NCI Cohort Consortium projects. Currently, none of the ancillary studies provides funding for ascertainment and validation of cancer (and CVD) endpoints. In the proposed funding period, we will continue the WHS infrastructure, including the follow-up and evaluation of self-reported exposures and endpoints, and maintenance of the WHS biospecimen repository, to further facilitate data sharing and collaboration. WHS is also committed to continuing to provide leadership in research aims related to gene-based prediction of incident disease and gene-environment interactions; improved assessments of physical activity and sedentary behavior to study associations with health outcomes, and evaluation of long-term chemoprotection of low-dose aspirin. Independent funding will be sought over the next period to address specific hypotheses in these areas. In the next 5 years, continued infrastructure support and follow-up is crucial for maximizing the cost-effective use of this valuable large-scale cancer cohort of women with a rich resource of already collected phenotypic and genetic data, particularly since many WHS findings have been and can be directly translated to clinical and public health practice or formal recommendations.