Associations of Metabolomic Predictors of Fat Amount and Distribution with Ca

项目总结（见说明）： 值得注意的是，健康的，身体活跃的成年人显示出脂肪分布，内脏肥胖水平相对较低-无论他们的整体肥胖。MEC中五个民族之间存在的肥胖水平和类型的异质性提供了一个独特的研究环境，以更好地了解BMI增加和脂肪分布变化的不良影响，包括其与癌症的关系。更具体地说，我们提出了一个一般性的观点，其中：（i）脂肪沉积在不同的身体脂肪储存室携带不同的癌症风险;（ii）瘦肉和脂肪组织的数量和身体分布在五个种族中不同 群体和解释一些观察到的种族差异，在癌症风险（特别是乳腺癌和结直肠癌）中观察到的MEC人口;（iii）身体脂肪量和分布通过相同的生物学机制，但在不同程度上对癌症promofion的MEC的五个种族群体。在这一观点的背景下，我们建议检验这一假设，即脂肪分布的生物标志物是足够强大的疾病风险的生物标志物，它们预测跨种族的疾病风险。目标： 目标1：开发、优化和验证一系列确定的嵌套血浆代谢组学生物标志物谱，以反映总体体脂背景下的相对和绝对脂肪分布。 目标二：确定肥胖和体脂分布的全身代谢组学特征与先前开发的热量摄入代谢组学特征以及膳食中大量营养素组成的类间和类内差异之间的相似性、差异性和相互作用。 目标3：在巢式病例对照研究中，使用从MEC（乳腺、结肠）和NHS（乳腺）前瞻性收集的生物标本，检验这些体脂量和分布预测因子与癌症风险的相关性。 目标4：将结果与其他项目的结果相结合，以便更好地了解潜在的生物学，更好地预测肥胖表型和癌症风险。 这些数据将通过改进肥胖与癌症风险之间联系的风险估计来改善公共健康。 这些数据将改善公众健康的风险评估之间的联系肥胖和癌症

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