Women's Health Study: Continued Follow-up

描述（由申请人提供）：该提案寻求资金，以继续对39，876名妇女健康研究（WHS）参与者进行为期5年的观察性随访，总体目标是积累和验证大量增加的癌症和心血管疾病（CVD）终点，以评估与生活方式，生化标志物，遗传标志物和基因-环境相互作用相关的临床重要问题。在每名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总癌症和CVD终点比研究前15年发生的数量增加57%至86%。 WHS始于1992年，是一项在39，876名年龄在45岁以上的女性卫生专业人员中进行的阿司匹林和维生素E在癌症和心血管疾病一级预防中的随机试验，在平均10年后于2004年结束。由> 28，000名参与者提供的预随机化血液样本被处理、冷冻和储存，并且联邦和非联邦资助允许进行广泛的血浆生物标志物分析和全基因组关联扫描（GWAS）。现在每年对妇女进行一次终点和风险因素问卷调查。15年后，发病率随访率超过90%，死亡率随访率几乎为100%。终点验证是最新的，对自我报告的癌症和CVD终点的89-95%的医疗记录进行了审查。因此，这项研究为研究妇女的重要健康问题提供了极其丰富的高质量数据资源。 除了总体目标外，该提案还特别寻求评价迄今为止样本量不足的问题。对于癌症，我们将通过以下研究来调查能量平衡、维生素D代谢和结直肠癌风险：（1）肥胖和体力活动对结直肠癌风险的相互作用;（2）肥胖相关基因变异和结直肠癌风险;（3）脂联素、相关基因变异和结直肠癌风险的关联;（4）与维生素D代谢和结直肠癌相关的基因变异。对于心血管疾病，该应用程序旨在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，这是一个未充分研究的群体。再加上5年的终点，现在的把握度足以解决这些问题。最后，用额外的癌症和CVD终点来增强现有的WHS生物储存库将允许与癌症，CVD和基因组联盟继续富有成效的合作，以回答有关遗传和环境风险因素以及基因-环境相互作用的问题（WHS已经完成了44项，目前资助了36项辅助研究）。未能确保额外的5年终点不仅会危及母研究，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GWAS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