Nutrition and Physical Activity Assessment Study

项目摘要 CA 119171 -12“营养和体力活动评估研究”（NPAAS）的竞争性更新 继续专注于开发新的饮食生物标志物和应用这些生物标志物， 调查饮食和癌症，心血管疾病和2型糖尿病的风险在妇女的健康 绝经后美国妇女的倡议（WHI）队列。我们的工作使用营养物质的客观生物标志物， 食物和饮食模式，使用在控制喂养研究中收集的血液和尿液生物标本， 食物和饮料的类型和数量是已知的。饮食生物标志物可以作为独立的 饮食评估，或者，正如本提案所强调的那样，它们可以扩展到 适用于使用回归校准方法的廉价疾病关联应用。进展 已作出了关于确定一些饮食变量的客观措施，为公众健康 应用，但是仍然存在对高维平台的有限使用（例如，血液和尿液中的代谢组学） 以实现此目的。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，如肉类，鱼类和添加糖，其中可能与慢性疾病有关。 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， 我们将解决。在这轮资助中，我们建议为这些研究领域做出贡献，并开展 将这些生物标志物摄入结果扩展到不同人群的普遍性研究， WHI.我们的具体目标是：1）进一步开发和评估食品，营养素和 根据NPAAS喂养研究（n=153）的数据提供的其他膳食化合物，并应用生物标志物 符合我们预先规定的NPAAS衍生标准，以检查与癌症风险、心血管疾病风险 绝经后妇女的WHI队列中的疾病和2型糖尿病（n= 161，808）; 2）测量血清 碳、氮同位素比值和氨基酸碳同位素比值作为鱼类/海产品、动物 NPAAS观察性研究（n=450）中的蛋白质和添加糖，并将这些措施应用于测试 与WHI队列中癌症、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志物（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 WHI组群中的疾病;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学生物标志物，用于两个对照组中的不同研究人群 喂养研究。我们富有成效的研究团队预计将作出额外的，创新的贡献， 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之上，即饮食摄入的生物标志物，作为独立的暴露或作为校准的工具， 自我报告，是至关重要的发展可靠的信息，饮食对慢性病风险的影响。

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.