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

妇女健康研究：为持续队列随访提供基础设施支持

• 批准号: 9130775
• 负责人: Julie E. Buring
• 金额: $ 83.11万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-17 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9130775
• 关键词: Accelerometer; Address; Ancillary Study; Aspirin; Beta Carotene; Biological Assay; Biological Markers; Blood; Blood specimen; Breast; Cardiovascular Diseases; Cause of Death; Cessation of life; Characteristics; Chronic Disease; Cohort Studies; Collaborations; Colorectal; DNA; Data; Data Quality; Death Certificates; Development; Disease; Dose; Epidemiologic Studies; Erythrocytes; Event; Funding; Future; Gene Frequency; Genes; Genetic; Genotype; Grant; Knowledge; Letters; Life Style; Lung; Malignant Neoplasms; Measurement; Measures; Medical History; Medical Records; Methods; Minor; Morbidity - disease rate; National Cancer Institute; Observational Study; Outcome; Paper; Patient Self-Report; Physical activity; Plasma; Policies; Process; Publishing; Quality Control; Questionnaires; Randomized Controlled Trials; Reporting; Research; Research Activity; Research Infrastructure; Research Personnel; Risk; Role; Sampling; Testing; Time; Translating; U-Series Cooperative Agreements; Update; Validation; Variant; Vitamin E; Woman; Women' s Health; Work; aged; base; cancer epidemiology; cancer prevention; cohort; cost effective; data management; data sharing; exome; follow-up; functional group; gene environment interaction; genetic information; genetic variant; genome wide association study; interest; member; mortality; prevent; rare variant; repository; web site; working group

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.

描述（由申请人提供）：WHS 于 1992 年开始，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 在 39,876 名年龄 > 45 岁的健康女性中预防癌症和心血管疾病 (CVD) 的效果，该试验于 2004 年结束从那时起，女性就开始接受观察性随访，每年，女性都会通过调查问卷报告各种暴露和终点，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因。在基线时，28,345 名女性还提供了血液样本，从中获取了血浆、血沉棕黄层和红细胞。并在 -170°C 下保存所有女性血液中的常见变异数据，刚刚完成了对超过 23,000 名女性的外显子组罕见变异的测量，并且所有样本均已完成；已通过加速度计对约 18,000 名女性进行了客观评估的身体活动，WHS 队列在进行 GWAS 方面是独一无二的，并且在如此大的队列中进行了客观评估的身体活动。近 20 年后，发病率随访率为 94%；死亡率随访率几乎为 100%。在当前资助结束时，有 6,086 例确诊癌症。 （2,440 例乳腺癌、583 例结直肠癌、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增加 30% 和 51%，WHS 已积极向内部和外部研究人员提供数据。在拟议的资助期内，我们计划发表 444 篇论文，资助 89 项辅助研究，并参与 19 个 NCI 队列联盟合作项目。 (1) 继续更新暴露和终点信息，并维护生物样本存储库，以进一步促进数据共享和协作，以及 (2) 使用 WHS 基础设施来实现与身体活动相关的具体目标；基于基因的风险并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。所有辅助研究都没有为癌症（和心血管疾病）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经济有效地利用这一宝贵的大规模女性群体至关重要，这些女性群体已经收集了丰富的表型和遗传数据。 相关性：本申请寻求未来 5 年内对妇女健康研究基础设施的支持，该研究是自 1992 年以来追踪的由 39,876 名女性组成的大规模癌症流行病学队列，可提供有关广泛特征、慢性疾病发展、血液生物标志物的数据、遗传信息和客观测量的身体活动对于在已收集的大量数据的基础上回答与癌症相关的关键问题至关重要。