Women's Health Study: Continued Follow-up

描述（由申请人提供）：本申请寻求资金，以继续对39,876名妇女健康研究（WHS）参与者进行额外5年的观察性随访，其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的总终点比研究的前15年增加57%至86%。WHS开始于1992年，是一项针对39,876名年龄在e45岁的女性卫生专业人员的阿司匹林和维生素E初级预防癌症和心血管疾病的随机试验，在平均10年后于2004年结束。由bbb28,000名参与者提供的预随机血液样本被处理、冷冻和储存，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）。现在对妇女进行观察性随访，每年进行终点和危险因素问卷调查。15年后，发病率随访超过90%，死亡率随访几乎为100%。终点验证是最新的，对89-95%的自我报告的癌症和心血管疾病终点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。除了总体目标之外，该建议还特别寻求评价迄今为止没有足够样本量的问题。对于癌症，我们将研究能量平衡、维生素D代谢和结直肠癌风险的各个方面，通过检查：(1)肥胖和体育活动对结肠癌风险的相互作用；(2)肥胖相关基因变异与结直肠癌风险；(3)脂联素、相关基因变异与结直肠癌风险的关系；(4)维生素D代谢与结直肠癌相关的基因变异。对于心血管疾病，该申请旨在评估女性中风亚型和功能结局的临床、生化和遗传风险因素，这是一个研究不足的群体。再加上5年的终端，现在的能力将足以解决这些问题。最后，增加现有的WHS生物库，增加更多的癌症和心血管疾病终点，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-环境相互作用的问题（WHS有44项完成的研究和36项目前资助的辅助研究）。如果不能确保额外的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已经可用的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 PUBLIC HEALTH RELEVANCE: The Women's Health Study (WHS) is an ongoing observational follow-up of the 39,876 initially healthy women who were enrolled in the WHS trial, begun in 1992, to evaluate the roles of low-dose aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease (CVD). The participants have now been followed for an average of 15 years, and extensive clinical and risk factor data have been collected over that time. Biochemical and genome-wide scan data are also available for the more than 28,000 participants who provided a baseline blood sample. This proposal requests funding for 5 more years of ascertainment and validation of cancer and CVD endpoints, to allow the evaluation of clinically important questions related to the influence of lifestyle, biochemical markers, genetic markers, and gene-environment interactions on cancer and CVD risk. 1