Women's Health Study: Continued Follow-up

描述(由申请人提供)：这项提案寻求资金，以继续对39,876名妇女健康研究(WHS)参与者进行为期5年的观察性跟踪，首要目标是积累和验证大幅增加的癌症和心血管疾病(CVD)终点，以评估与生活方式、生化标记、遗传标记和基因-环境相互作用有关的临床重要问题。在每个参与者的增量成本非常低的情况下，增加5年的观察性随访将使癌症和心血管疾病终点总数比研究前15年的数字增加57%至86%。WHS始于1992年，最初是一项阿司匹林和维生素E在癌症和心血管疾病一级预防中的随机试验，对象为39,876名年龄为45岁的女性卫生专业人员，平均10年后于2004年结束。由28,000名参与者提供的随机化前血液样本被处理、冷冻和存储，联邦和非联邦资金允许进行广泛的血浆生物标记物分析和全基因组关联扫描(GWAS)。现在对女性进行观察性跟踪，每年进行终点和风险因素问卷调查。15年后，发病率随访率远高于90%，死亡率随访率几乎为100%。终点验证是最新的，可以审查89%-95%的自我报告癌症和心血管疾病终点的医疗记录。因此，这项研究为研究女性的重要健康问题提供了极其丰富的高质量数据来源。除了总体目标之外，该提案还特别寻求评估到目前为止样本量不足的问题。对于癌症，我们将通过以下方面来研究能量平衡、维生素D代谢和结直肠癌风险：(1)肥胖和体力活动对结肠癌风险的交互作用；(2)肥胖相关基因变体和结直肠癌风险；(3)脂联素、相关基因变量和结直肠癌风险的关系；以及(4)与维生素D代谢和结直肠癌相关的基因变量。对于心血管疾病，该应用程序寻求评估中风亚型的临床、生化和遗传风险因素以及女性中风的功能结果，这是一个研究不足的群体。有了额外的5年终端，电力现在将足以解决这些问题。最后，用更多的癌症和心血管疾病终点扩大现有的WHS生物库，将允许与癌症、心血管疾病和基因组联盟继续进行富有成效的合作，以回答有关遗传和环境风险因素以及基因与环境相互作用的问题(WHS已完成44项研究，目前已资助36项辅助研究)。如果不能获得额外5年的终点，不仅会危及母研究，而且还会危及所有辅助研究以及利用这一极其宝贵的数据资源和已有的全球气候变化系统的能力。1

DESCRIPTION (provided by applicant):This proposal seeks funding to continue observational follow-up of the 39,876 Women's Health Study (WHS) participants for an additional 5 years, with the overarching aim of accruing and validating a substantially increased number of both cancer and cardiovascular disease (CVD) endpoints to evaluate clinically important questions related to lifestyle, biochemical markers, genetic markers, and gene-environment interactions. At a very low incremental cost per participant, an added 5 years of observational follow-up will increase total cancer and CVD endpoints by 57% to 86% over the numbers occurring in the first 15 years of the study. The WHS began in 1992 as a randomized trial of aspirin and vitamin E in the primary prevention of cancer and CVD among 39,876 female health professionals aged e45 years, ending in 2004 after a mean of 10 years. Pre-randomization blood samples provided by >28,000 participants were processed, frozen, and stored, and federal and non-federal funding has allowed the conduct of extensive plasma biomarker analyses and a whole genome association scan (GWAS). Women are now followed observationally with yearly endpoint and risk factor questionnaires. After 15 years, morbidity follow-up is well over 90% and mortality follow-up is virtually 100%. Endpoint validation is up to date, with review of 89-95% of medical records completed for self-reported cancer and CVD endpoints. Thus, this study represents an extremely rich resource of high-quality data for studying important health concerns in women. In addition to the overarching aim, the proposal specifically seeks to evaluate questions that have not had adequate sample sizes to date. For cancer, we will investigate aspects of energy balance, vitamin D metabolism, and colorectal cancer risk by examining: (1) the interaction between obesity and physical activity on colon cancer risk; (2) obesity-associated gene variants and colorectal cancer risk; (3) the associations of adiponectin, related gene variants, and colorectal cancer risk; and (4) gene variants related to vitamin D metabolism and colorectal cancer. For CVD, the application seeks to evaluate clinical, biochemical, and genetic risk factors for subtypes of stroke and functional outcomes from stroke in women, an understudied group. With an additional 5 years of endpoints, power will now be adequate to address these questions. Finally, augmenting the existing WHS biorepository with additional cancer and CVD endpoints will allow continued fruitful collaborations with cancer, CVD, and genomic consortia to answer questions regarding genetic and environmental risk factors and gene-environment interactions (the WHS has 44 completed and 36 currently funded ancillary studies). Failure to secure an additional 5 years of endpoints will jeopardize not only the parent study, but also all ancillary studies as well as the ability to capitalize on this enormously valuable data resource and GWAS already available. 1