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

妇女健康研究：队列随访的基础设施支持

• 批准号: 10241244
• 负责人: Julie E. Buring
• 金额: $ 71.53万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241244
• 关键词: Address; Age; Aging; Ancillary Study; Area; Aspirin; Behavior; Beta Carotene; Biological Assay; Biological Markers; Biological Specimen Banks; Blood; Blood specimen; Cardiovascular Diseases; Cause of Death; Cessation of life; Characteristics; Chemoprotection; Chronic Disease; Clinical; Cohort Studies; Collaborations; DNA; Data; Data Collection; Death Certificates; Development; Devices; Disease; Dose; Erythrocytes; Evaluation; Event; Follow-Up Studies; Funding; Funding Agency; Funding Mechanisms; Future; Genes; Genetic; Genotype; Grant; Growth; Health; Individual; Infrastructure; Knowledge; Leadership; Maintenance; Malignant Neoplasms; Measures; Medical Records; Metabolic Diseases; Methodology; Methods; Monitor; Morbidity - disease rate; Multiple Cancer Sites; Observational Study; Outcome; Paper; Participant; Patient Self-Report; Pattern; Phenotype; Physical activity; Physical assessment; Plasma; Primary Cancer Prevention; Public Health Practice; Publishing; Quality Control; Questionnaires; Randomized; Recommendation; Reporting; Research; Research Activity; Research Personnel; Research Project Grants; Resources; Risk Factors; Role; Sampling; Self-Examination; Site; Testing; Time; Translating; United States Centers for Medicare and Medicaid Services; Update; Validation; Vitamin E; Woman; Women' s Health; Work; base; cancer epidemiology; cancer prevention; cohort; cost effective; data integration; data management; data quality; data sharing; epidemiology study; exome; follow-up; gene environment interaction; genetic analysis; genetic association; genetic information; genome wide association study; genome-wide; improved; member; mortality; neoplasm resource; randomized trial; rare cancer; research study; sedentary lifestyle; tumor; virtual; web site

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.

该提案仅寻求核心职能的基础设施支持，以进行 5 年的持续跟进 妇女健康研究 (WHS)，见 PAR-17-233。 WHS 始于 1992 年，是一项随机试验 阿司匹林、β-胡萝卜素和维生素 E 可预防 39,876 人的癌症和心血管疾病 (CVD) 45 岁以上的健康女性。在随机分组之前，28,345 名女性 (71%) 提供了血液样本：全部都采集了血液样本 已对多种生物标志物进行了检测；全基因组关联研究（GWAS） 完成了超过 25,000 个样本，并完成了超过 22,000 个样本的外显子组芯片基因分型。该试验于 2004 年结束，有 33,682 名患者（即 89%） 的幸存妇女愿意接受观察跟踪。妇女通过年度调查问卷报告 广泛的暴露和终点；我们通过医疗机构确认自我报告的癌症和心血管疾病终点 病历和/或死亡证明中的死亡原因。设备评估 7 天身体状况 收集了 17,708 名女性的活动和久坐行为。 WHS 的独特之处在于拥有广泛的 如此大的人群中的遗传数据以及客观评估的身体活动和久坐行为。 随访非常出色：近 24 年过去了，发病率随访仍为 89.6%%，死亡率随访率为 几乎 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增加： 在当前资助结束时（2019 年 8 月 31 日），将有 7,769 例确诊癌症发生；到提议结束时 资助周期（8/31/24），将确认 10,869 例癌症。这将大大提高 WHS 的能力 解决重要的癌症问题，包括检查特定部位的癌症、罕见的癌症和肿瘤 具体特征。 WHS 积极与内部和外部研究人员共享数据，从而 发表了 650 篇论文，利用 WHS 数据资助了 106 项资助，并在 22 个 NCI 队列联盟中进行了合作 项目。目前，没有任何辅助研究为癌症的确定和验证提供资金 （和 CVD）终点。 在拟议的资助期内，我们将继续WHS基础设施，包括后续和评估 自我报告的暴露和终点，以及 WHS 生物样本库的维护，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发挥领导作用 与基于基因的疾病事件预测和基因-环境相互作用相关的目标；改进的 评估身体活动和久坐行为，以研究与健康结果的关联，以及 评估小剂量阿司匹林的长期化学保护作用。下一步将寻求独立资金 时间来解决这些领域的具体假设。未来5年，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癌症女性群体的成本效益利用至关重要 拥有已收集的表型和遗传数据的丰富资源，特别是因为许多 WHS 发现 已经并且可以直接转化为临床和公共卫生实践或正式建议。