The Women's Health Study: Infrastructure Support for Continued Cohort Follow-up

描述(申请人提供)：WHS始于1992年，是一项随机对照试验，在39,876名45岁的健康妇女中测试阿司匹林、β-胡萝卜素和维生素E预防癌症和心血管疾病(CVD)，试验于2004年结束，自那时以来一直对妇女进行观察跟踪。在研究开始时和每年，妇女通过问卷报告广泛的暴露和终点，包括癌症和心血管疾病。我们用医疗记录确认这些自我报告的终点，并使用医疗记录和死亡证明确定死者的死因。在基线时，28,345名妇女还提供了血液样本，从中获取血浆、棕黄色外套和红细胞并存储在-170℃。所有有血液的妇女都有关于常见变异的数据，刚刚完成了对23,000名妇女外显体罕见变异的测量；所有样本都已进行了几个生物标志物的分析。通过加速计对大约18,000名女性进行了7天的客观体力活动评估。世界卫生组织的队列是独一无二的，在如此大的队列中有GWA和客观地评估体力活动。随访率很高；近20年后，发病率随访率为94%，死亡率随访率几乎为100%。在当前供资结束时，将发生6086例确诊癌症(2440例乳腺癌、583例结直肠癌、537例肺癌、1517例癌症死亡)。在拟议的资助期内，癌症和心血管疾病终点将增加30%和51%。世界卫生组织积极向内部和外部研究人员提供数据，发表了444篇论文，资助了89项辅助研究，并参与了NCI队列联盟的19个合作项目。在拟议的资助期内，我们打算：(1)继续更新暴露和终点信息，并维护生物样本储存库，以进一步促进数据共享和合作，以及(2)使用WHS基础设施来解决与体力活动相关的特定目标；评估基于基因的风险的翻译潜力并探索基因与环境的相互作用；以及研究小剂量阿司匹林对癌症的长期化学保护作用。没有一项辅助研究为癌症(和心血管疾病)终点的确定和验证提供资金。持续的基础设施支持和后续行动对于最大限度地以高成本效益利用这一拥有大量已收集的表型和基因数据的宝贵的大规模妇女群体至关重要。 相关性：这项申请寻求在未来5年为妇女健康研究的基础设施提供支持，这是自1992年以来对39,876名妇女进行的大规模癌症流行病学队列研究，可获得关于各种特征、慢性病发展、血液生物标记物、遗传信息和客观测量的体力活动的数据。继续跟进对于建立在已经收集的大量数据的基础上，以回答与癌症有关的关键问题至关重要。

DESCRIPTION (provided by applicant): The WHS began in 1992 as a randomized controlled trial testing aspirin, beta-carotene, and vitamin E for preventing cancer and cardiovascular disease (CVD) in 39,876 healthy women, aged >45, The trial ended in 2004, and women have been followed observationally since that time. At study entry and annually, women report via questionnaires on a wide range of exposures and endpoints, including cancer and CVD. We confirm these self-reported endpoints with medical records, and cause of death in decedents is ascertained using medical records and death certificates. At baseline, 28,345 women also provided a blood sample, from which plasma, buffy coat, and red blood cells were obtained and stored at -170 C. GWAS data on common variation are available for all women with blood, measurement of rare variants in exomes have just been completed for >23,000 women; and all samples have been assayed for several biomarkers. Objectively assessed 7-day physical activity by accelerometer is being collected on ~18,000 women. The WHS cohort is unique in having GWAS and objectively-assessed physical activity in such a large cohort. Follow-up is excellent; after almost 20 years, morbidity follow-up is 94 percent; and mortality follow-up is virtually 100 percent. At the end of current funding, 6,086 confirmed cancers (2,440 breast, 583 colorectal, 537 lung, 1,517 cancer deaths) will have occurred. During the proposed funding period, cancer and CVD endpoints will increase by 30 percent and 51 percent. The WHS has actively provided data to internal and external researchers, with 444 papers published, 89 ancillary studies funded, and participation in 19 NCI Cohort Consortium collaborative projects. In the proposed funding period, we intend to: (1) continue to update exposure and endpoint information, and maintain the repository of biospecimens, to further facilitate data sharing and collaboration, and (2) use the WHS infrastructure to address specific aims related to physical activity; evaluate the translational potential of gene-based risk and explore gene-by-environment interactions; and examine long-term chemo-protection of low-dose aspirin on cancer. None of the ancillary studies provides funding for ascertainment and validation of cancer (and CVD) endpoints. Continued infrastructure support and follow-up is crucial for maximizing the cost-effective use of this valuable large-scale cohort of women with a rich bank of already collected phenotypic and genetic data. RELEVANCE: This application seeks support over the next 5 years for the infrastructure of the Women's Health Study, a large-scale cancer epidemiology cohort of 39,876 women followed since 1992, Data are available on a wide range of characteristics, chronic disease development, blood biomarkers, genetic information, and objectively measured physical activity. Continued follow-up is crucial for building on the enormous amount of data already collected in order to answer critical questions related to cancer.