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

该提案仅寻求核心功能的基础设施支持，以进行为期5年的持续跟踪 妇女健康研究(WHS)，低于标准杆17-233。WHS始于1992年，最初是一项随机试验测试 阿司匹林、β-胡萝卜素和维生素E预防癌症和心血管疾病(CVD)的人数为39876人 45岁以上的健康女性。在随机化之前，28,345名女性(71%)提供了血样：所有人都有 已经对广泛的生物标记物进行了分析；全基因组关联研究(GWAS)已经 在&gt；25,000上完成了基因分型，在&gt；22,000上完成了外显子芯片基因分型。审判于2004年结束，33,682人(或% 的幸存女性愿意接受观察跟踪。女性通过每年一次的问卷调查 广泛的暴露和终点；我们通过医学检查确认自我报告的癌症和心血管疾病终点 病历、病历和/或死亡证明的死亡原因。设备评估7天体检 对17,708名女性的活动和久坐行为进行了收集。WHS的独特之处在于拥有广泛的 基因数据以及对如此大的队列中的体力活动和久坐行为的客观评估。 随访情况良好：近24年后，发病率随访率仍为89.6%，死亡率随访率为 几乎是100%。由于在世参与者的平均年龄为77.1岁，事件发生率正在大幅上升： 在当前供资结束时(19年8月31日)，将发生7769例确诊癌症；到拟议的 在供资周期(8/31/24)期间，将确认10,869种癌症。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- 特定的特征。世界卫生组织积极与内部和外部研究人员分享数据，结果 发表了650篇论文，使用WHS数据资助了106笔赠款，并与22个NCI队列联盟进行了合作 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 (和CVD)终端。 在拟议的资助期内，我们将继续实施世界卫生组织的基础设施，包括后续行动和评估 自我报告的暴露和终点，以及维护世界卫生组织生物质库，以进一步 促进数据共享和协作。WHS还致力于继续在研究领域提供领先地位 与基于基因的疾病发生预测和基因-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系，以及 小剂量阿司匹林长期化学保护作用的评价在接下来的一年里将寻求独立的资金 解决这些领域的具体假设的时期。在未来5年，继续提供基础设施支持和 随访对于最大限度地成本效益地利用这一有价值的大规模癌症妇女队列至关重要。 拥有丰富的已经收集的表型和遗传数据资源，特别是在世界卫生组织的许多发现 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.