Associations of Metabolomic Predictors of Fat Amount and Distribution with Ca

脂肪量和分布的代谢组学预测因子与 Ca 的关联

• 批准号: 8374226
• 负责人: BRUCE S KRISTAL
• 金额: $ 64.48万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8374226
• 关键词: Abdomen; Adult; Biological; Biological Markers; Biology; Body fat; Body mass index; Breast; Categories; Clinical Trials; Colon; Colorectal Cancer; Data; Data Set; Deposition; Diet; Dimensions; Dual-Energy X-Ray Absorptiometry; Electrodes; Electronics; Energy Intake; Epidemiology; Ethnic Origin; Ethnic group; Fatty acid glycerol esters; Future; Gender; Heterogeneity; High Pressure Liquid Chromatography; Image; Individual; Informatics; Instruction; Link; Macronutrients Nutrition; Malignant Neoplasms; Measurement; Methods; Metric; Modeling; Neoplasms; Nested Case-Control Study; Nurses' Health Study; Obesity; Participant; Phenotype; Plasma; Population; Proxy; Public Health; Published Comment; Race; Rattus; Relative (related person); Research; Resources; Risk; Risk Estimate; Series; Techniques; Testing; Tissues; Underweight; Visceral; Waist-Hip Ratio; Workplace; base; cancer risk; case control; cohort; cost; disorder risk; ethnic difference; falls; feeding; human population study; improved; interest; malignant breast neoplasm; metabolomics; nutritional epidemiology; predictive modeling; programs; waist circumference

PROJECT SUMMARY (See instructions): Notably, healthy, physically active adults display a fat distribution with a relatively low level of visceral adiposity - regardless of their overall adiposity. The heterogeneity in level and types of obesity that exists among the five ethnic groups in the MEC offers a unique research setting to better understand the ill effects of increases in BMI and shifts in distribution of fat, including its relationship to cancer. More specifically, we propose a general viewpoint in which: (i) Fat deposition in various body fat storage compartments carries different risks of cancer; (ii) Amount and body distribution of lean and fat tissue vary across the five ethnic groups and explain some of the observed ethnic differences in cancer risk (particularly for breast and colorectal cancer) observed in the MEC population; (iii) Body fat amount and distribution act on cancer promofion through the same biological mechanisms but to different extents in the five ethnic groups of the MEC. In the context of this view, we propose to test the hypothesis that biomarkers of fat distribution are sufficiently robust biomarkers of disease risk that they predict disease risk across ethnic groups. The Aims: Aim 1: To develop, optimize, and validate a defined series of nested plasma metabolomic biomarker profiles that reflect relative and absolute fat distribution in the context of overall body fat. Aim 2: To determine the similarities, differences, and interactions between the systemic metabolomic profiles of adiposity and body fat distribution and previously developed metabolomic profile(s) for caloric intake and dietary inter- and intra-class differences in macronutrient composition. Aim 3: To test the associations of these predictors of body fat amount and distribution with cancer risk in nested case-control studies using the prospectively collected biospecimens from the MEC (breast, colon) and the NHS (breast). Aim 4: To integrate results with those of the other projects in order to gain a better understanding of the underlying biology and better predict adiposity phenotypes and cancer risk. These data will improve public health by refining risk estimates of the links between adiposity and cancer risk. These data will improve public health by refining risk esfimates of the links between adiposity and cancer

项目摘要（请参阅说明）： 值得注意的是，健康，身体活跃的成年人表现出脂肪分布，内脏肥胖水平相对较低 - 无论其整体肥胖如何。 MEC五个族裔之间存在的肥胖水平和类型的异质性提供了独特的研究环境，以更好地了解BMI增加和脂肪分布的不良影响，包括其与癌症的关系。更具体地说，我们提出了一个一般观点，其中：（i）各种体内脂肪储物室中的脂肪沉积具有不同的癌症风险； （ii）瘦肉和脂肪组织的数量和身体分布在五个民族中各不相同 小组并解释了MEC人群中观察到的癌症风险（尤其是乳腺癌和大肠癌）中观察到的一些种族差异； （iii）通过相同的生物学机制对癌症表达的体内脂肪量和分布作用，但在MEC的五个族裔中的不同范围。在这种观点的背景下，我们建议检验以下假设：脂肪分布的生物标志物是疾病风险的足够强大的生物标志物，以预测整个族裔疾病的风险。目的： 目标1：开发，优化和验证一系列定义的嵌套血浆代谢组生物标志物谱，这些轮廓反映了整体体内脂肪中相对和绝对脂肪的分布。 目的2：确定肥胖和体内脂肪分布的全身代谢组谱之间的相似性，差异和相互作用，以及以前开发的代谢组概况，用于热量摄入和饮食中大量营养素组成的饮食间和饮食间差异。 目的3：使用来自MEC（乳腺癌，结肠）和NHS（乳腺癌）的前瞻性收集的生物质量研究，在嵌套病例对照研究中，体内脂肪量和分布与癌症风险的相关性。 目标4：将结果与其他项目的结果整合在一起，以便更好地了解潜在的生物学并更好地预测肥胖表型和癌症风险。 这些数据将通过完善肥胖与癌症风险之间联系的风险估计来改善公共卫生。 这些数据将通过完善肥胖与癌症之间联系的风险evimimates来改善公共卫生