Women's Health Study: Continued Follow-up

女性健康研究：持续随访

• 批准号: 8209207
• 负责人: Julie E. Buring
• 金额: $ 181.34万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8209207
• 关键词: 25-hydroxyvitamin D; Address; Ancillary Study; Androgen Receptor; Apolipoprotein A-I; Arthritis; Aspirin; Biochemical; Biochemical Genetics; Biochemical Markers; Biological; Biological Assay; Biological Markers; Blood Vessels; Blood specimen; Brain hemorrhage; Breast; C-reactive protein; Cancer Etiology; Cardiovascular Diseases; Cause of Death; Cholesterol; Chronic Disease; Clinical; Clinical Trials; Collaborations; Collection; Colon Carcinoma; Colorectal; Colorectal Cancer; Connective Tissue Diseases; Creatinine; DNA; Data; Data Quality; Data Set; Data Sources; Development; Diabetes Mellitus; Dose; Enrollment; Environmental Risk Factor; Enzymes; Epidemiology; Evaluation; Event; Eye diseases; Failure; Fatty acid glycerol esters; Fibrinogen; Freezing; Funding; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Risk; Genetic Variation; Genome; Genomics; Genotype; Glycosylated hemoglobin A; Grant; Health; Health Professional; Hemoglobin; Hemostatic function; High Density Lipoprotein Cholesterol; Homocysteine; Homocystine; Hormones; Hypertension; Impaired cognition; Incidence; Individual; Inflammation; Intercellular Adhesion Molecules; Investigation; Ischemic Stroke; LDL Cholesterol Lipoproteins; Life Style; Lipids; Lipoprotein (a); Mails; Malignant Neoplasms; Malignant neoplasm of lung; Mediator of activation protein; Medical; Medical History; Medical Records; Melanocortin 4 Receptor; Metabolism; Migraine; Modification; Morbidity - disease rate; Myocardial Infarction; National Heart, Lung, and Blood Institute; Obesity; Outcome; Parents; Participant; Pathway interactions; Patient Self-Report; Pattern; Peripheral arterial disease; Physical activity; Plasma; Predisposition; Primary Cancer Prevention; Process; Publications; Questionnaires; RXRA gene; RXRB gene; RXRG gene; Randomized; Recording of previous events; Reporting; Request for Proposals; Research; Research Infrastructure; Resources; Restless Legs Syndrome; Risk; Risk Factors; Role; Sample Size; Sampling; Scanning; Secure; Signal Transduction; Single Nucleotide Polymorphism; Site; Smoking; Specific qualifier value; Stroke; Thromboembolism; Thrombosis; Time; Triglycerides; United States National Institutes of Health; Validation; Variant; Venous; Vitamin D; Vitamin E; Woman; Women' s Health; adiponectin; aged; apolipoprotein B-100; base; biobank; cancer risk; cardiovascular disorder risk; case control; cohort; cost; cost effective; density; disability; double-blind placebo controlled trial; energy balance; follow-up; functional outcomes; gene environment interaction; genetic analysis; genetic resource; genetic risk factor; genome wide association study; lifestyle factors; mortality; novel; oncology; prevent; public health relevance; randomized trial; receptor; sudden cardiac death; treatment duration

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

描述（由申请人提供）：该提案寻求资金，以继续对 39,876 名女性健康研究 (WHS) 参与者进行额外 5 年的观察性随访，总体目标是积累和验证数量大幅增加的癌症和心血管疾病 (CVD) 终点，以评估与生活方式、生化标志物、遗传标志物和基因环境相关的临床重要问题 互动。每位参与者的增量成本非常低，增加 5 年的观察性随访将使癌症和 CVD 终点总数比研究前 15 年发生的数字增加 57% 至 86%。 WHS 始于 1992 年，当时是一项阿司匹林和维生素 E 在癌症和 CVD 一级预防中的随机试验，受试者为 39,876 名 45 岁以下的女性卫生专业人员，平均为期 10 年，于 2004 年结束。对超过 28,000 名参与者提供的随机化前血液样本进行了处理、冷冻和储存，联邦和非联邦资金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)。现在每年对女性进行终点和危险因素调查问卷进行观察性跟踪。 15 年后，发病率随访率远超 90%，死亡率随访率几乎为 100%。终点验证是最新的，已完成自我报告癌症和心血管疾病终点医疗记录的审查 89-95%。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资源。 除了总体目标外，该提案还特别寻求评估迄今为止样本量不足的问题。对于癌症，我们将通过检查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) 肥胖和体力活动之间的相互作用对结直肠癌风险的影响； (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联； (4)维生素D代谢与结直肠癌相关的基因变异。对于 CVD，该应用程序旨在评估中风亚型的临床、生化和遗传危险因素以及女性（一个未被充分研究的群体）中风的功能结果。再过 5 年的终点，现在就足以解决这些问题。最后，通过额外的癌症和 CVD 终点来扩充现有的 WHS 生物存储库，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 已完成 44 项辅助研究，目前资助了 36 项辅助研究）。如果无法获得额外 5 年的终点，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现有 GWAS 的能力。 1 公共健康相关性：女性健康研究 (WHS) 是对 39,876 名最初健康的女性进行的持续观察性随访，这些女性参加了 1992 年开始的 WHS 试验，旨在评估低剂量阿司匹林和维生素 E 在癌症和心血管疾病 (CVD) 一级预防中的作用。目前，参与者的平均随访时间为 15 年，在此期间收集了大量的临床和危险因素数据。还提供了 28,000 多名提供基线血液样本的参与者的生化和全基因组扫描数据。该提案要求再资助 5 年的癌症和 CVD 终点的确定和验证，以便评估与生活方式、生化标记、遗传标记以及基因-环境相互作用对癌症和 CVD 风险的影响相关的临床重要问题。 1