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

描述（由申请人提供）：WHS开始于1992年，是一项随机对照试验，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）的效果，试验于2004年结束，从那时起对妇女进行观察性随访。在研究开始和每年，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。我们用医疗记录证实了这些自我报告的终点，并利用医疗记录和死亡证明确定了死者的死亡原因。在基线时，28345名妇女也提供了血液样本，从这些样本中获得血浆、黄皮毛和红细胞，并在-170℃下储存。GWAS对所有有血液的妇女都有常见变异的数据，对23000名妇女的外显子组的罕见变异的测量刚刚完成；所有样本都检测了几种生物标记物。通过加速度计对约18,000名妇女进行了7天的客观身体活动评估。在如此庞大的队列中，WHS队列的独特之处在于具有GWAS和客观评估的身体活动。后续工作非常出色；经过近20年的随访，发病率为94%；死亡率几乎是100%。在目前的资助结束时，将发生6 086例确诊癌症（2 440例乳腺癌、583例结肠直肠癌、537例肺癌、1 517例癌症死亡）。在拟议的资助期内，癌症和心血管疾病终点将分别增加30%和51%。WHS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19个NCI队列联盟合作项目。在拟议的资助期内，我们打算：(1)继续更新暴露和终点信息，并维护生物标本库，以进一步促进数据共享和协作；(2)使用WHS基础设施来解决与体育活动相关的具体目标；评估基因风险的转化潜力，探索基因与环境的相互作用；并检查低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确定和验证癌症（和心血管疾病）终点提供资金。持续的基础设施支持和后续工作对于最大限度地经济有效地利用这一有价值的大规模妇女队列以及已收集的丰富表型和遗传数据至关重要。

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.