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

描述（由申请人提供）：WHS始于1992年，作为一项随机对照试验，在39，876名年龄>45岁的健康女性中测试阿司匹林，β-胡萝卜素和维生素E预防癌症和心血管疾病（CVD），该试验于2004年结束，自那时以来一直对女性进行观察。在研究开始时和每年，女性通过问卷报告广泛的暴露和终点，包括癌症和心血管疾病。我们通过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亡原因。在基线时，28，345名妇女还提供了血液样本，从中获得血浆、血沉棕黄层和红细胞，并储存在-170 ℃下。GWAS关于常见变异的数据可用于所有有血液的女性，对外显子组中罕见变异的测量刚刚完成了> 23，000名女性;所有样本都已进行了几种生物标志物的测定。通过加速度计客观评估的7天身体活动正在收集约18，000名女性。WHS队列在如此大的队列中具有GWAS和客观评估的身体活动方面是独一无二的。随访非常好;近20年后，发病率随访率为94%;死亡率随访率几乎为100%。在目前的资金结束时，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）。在拟议的资助期间，癌症和CVD终点将增加30%和51%。WHS积极为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。在建议的资助期内，我们打算：（1）继续更新暴露和终点信息，并维护生物标本的储存库，以进一步促进数据共享和合作，以及（2）利用WHS基础设施实现与体力活动相关的特定目标;评估基因风险的转化潜力，并探索基因与环境的相互作用;并检测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癌症（和CVD）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提高这一宝贵的大规模妇女队列的成本效益至关重要，这些妇女拥有已收集的丰富的表型和遗传数据库。 相关性：该申请寻求在未来5年内支持妇女健康研究的基础设施，这是一项自1992年以来跟踪的39，876名妇女的大规模癌症流行病学队列，可获得有关各种特征，慢性疾病发展，血液生物标志物，遗传信息和客观测量的身体活动的数据。持续的后续行动对于建立在已经收集的大量数据基础上，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.