Nutrition and Physical Activity Assessment Study

项目总结 CA119171-12《营养与体力活动评估研究》(NPAAS)的竞争性更新 继续致力于开发新型膳食生物标记物，并将这些生物标记物应用于 饮食与癌症、心血管疾病、2型糖尿病风险在女性健康中的调查 绝经后美国妇女的倡议(WHI)队列。我们的工作使用了客观的营养生物标记物， 在受控喂养研究中收集的使用血液和尿液生物样本的食物和饮食模式 食品和饮料的类型和数量是已知的。膳食生物标记物可以单独使用。 对饮食的评估，或者，正如本提案中强调的，它们可能能够扩展到使它们 适用于使用回归校正方法的廉价疾病关联应用。进展 对一些影响公众健康的饮食变量的客观指标进行了识别 应用，但高维平台的使用仍然有限(例如，血液和尿液中的代谢组学) 为了这个目的。稳定同位素生物标志物的发现和评价也需要进一步的发展。 重要的饮食成分，如肉、鱼和添加的糖，其中可能与慢性 疾病风险。健康饮食模式的客观衡量标准的发现和验证是另一个差距 我们将发表讲话。在这个资金周期中，我们建议对这些研究领域作出贡献，并开展 将这些生物标记物摄入结果推广到不同人群的概括性研究 怎么了。我们的具体目标是：1)进一步开发和评估食品、营养素和 来自NPAAS喂养研究数据的其他饮食化合物(n=153)和应用生物标记物 符合我们预先指定的NPAAS衍生标准，以检查与癌症、心血管疾病风险的关联 绝经后妇女WHI队列中的疾病和2型糖尿病(n=161,808)；2)测定血清 碳、氮同位素比值和氨基酸碳同位素比值作为鱼/海产品、动物生物标志物的研究 NPAAS观察性研究中的蛋白质和添加糖(n=450)，并将这些措施应用于测试 在WHI队列中与癌症、心血管疾病和糖尿病风险的相关性；3)识别和 评估健康饮食模式的候选饮食生物标记物(例如，健康饮食指数、替代 地中海饮食评分)，用于测试这些饮食模式与同一组慢性疾病之间的关联 WHI队列中的疾病；以及4)使用血液和尿液代谢组学来测试新的 在NPAAS喂养研究中确定的代谢组生物标记物在两个对照的不同研究人群中 喂食研究。我们富有成效的研究团队有望为以下方面做出更多创新贡献 营养流行病学研究和更广泛的慢性病预防研究。我们的研究 建立在这样一种理解的基础上，即饮食摄入量的生物标志物，作为独立暴露或作为校准工具 自我报告对于发展关于饮食对慢性病风险的影响的可靠信息至关重要。

PROJECT SUMMARY This competing renewal of CA119171-12 “Nutrition and Physical Activity Assessment Study” (NPAAS) continues to focus on the development of novel dietary biomarkers and application of these biomarkers to investigations of diet and cancer, cardiovascular disease and type 2 diabetes risk in the Women’s Health Initiative (WHI) cohorts of postmenopausal U.S. women. Our work uses objective biomarkers of nutrients, foods and dietary patterns using blood and urine biospecimens collected in controlled feeding studies where types and quantities of foods and beverages are known. The dietary biomarkers can be used as stand-alone assessments of diet or, as emphasized in this proposal, they may be able to be extended to make them suitable for inexpensive disease association applications using a regression calibration approach. Progress has been made on the identification of objective measures of some dietary variables for public health applications, but there is still limited use of high-dimensional platforms (e.g., metabolomics in blood and urine) for this purpose. Further development is also needed for discovery and evaluation of stable isotope biomarkers of important dietary components, such as meat, fish and added sugars, where there are likely links to chronic disease risk. The discovery and validation of objective measures of healthy dietary patterns is another gap that we will address. In this cycle of funding, we propose to contribute to these research areas and to carry out generalizability studies toward extending these biomarker-intake results to diverse populations beyond the WHI. Our specific aims are: 1) To develop further and evaluate candidate biomarkers of foods, nutrients and other dietary compounds informed by data from the NPAAS feeding study (n=153) and to apply biomarkers meeting our prespecified NPAAS-derived criteria to examine associations with risk of cancer, cardiovascular disease and type 2 diabetes in WHI cohorts of postmenopausal women (n=161,808); 2) To measure serum carbon and nitrogen isotope ratios and amino acid carbon isotope ratios as biomarkers of fish/seafood, animal protein and added sugars in the NPAAS Observational Study (n=450) and to apply these measures to test associations with risk of cancer, cardiovascular disease and diabetes in WHI cohorts; 3) To identify and evaluate candidate dietary biomarkers of healthy eating patterns (e.g., Healthy Eating Index, Alternative Mediterranean Diet Score) for testing associations between these eating patterns with the same set of chronic diseases in WHI cohorts; and 4) To test, using blood and urine metabolomics, the generalizability of novel metabolomic biomarkers identified in the NPAAS feeding study to diverse study populations in two controlled feeding studies. Our productive research team is expected to make additional, innovative contributions to nutritional epidemiology research and more broadly to chronic disease prevention research. Our research builds on the understanding that biomarkers of dietary intake, as stand-alone exposures or as tools to calibrate self-report, are crucial to the development of reliable information on the effects of diet on chronic disease risk.