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（参见说明）： 值得注意的是，健康、体力活跃的成年人表现出内脏肥胖水平相对较低的脂肪分布——无论他们的整体肥胖程度如何。 MEC 五个种族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，可以更好地了解 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，我们提出了一个普遍的观点，其中：（i）不同身体脂肪储存室中的脂肪沉积具有不同的癌症风险； (ii) 五个种族的瘦肉组织和脂肪组织的数量和身体分布各不相同 群体并解释在 MEC 人群中观察到的一些癌症风险（特别是乳腺癌和结直肠癌）的种族差异； (iii) 身体脂肪量和分布通过相同的生物机制促进癌症的发生，但在 MEC 的五个种族群体中作用程度不同。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足够强大的疾病风险生物标志物，可以预测跨种族群体的疾病风险。目标： 目标 1：开发、优化和验证一系列明确的嵌套血浆代谢组生物标志物谱，反映整体脂肪背景下的相对和绝对脂肪分布。 目标 2：确定肥胖和身体脂肪分布的系统代谢组学概况与先前开发的热量摄入代谢组学概况以及膳食宏量营养素成分的组间和组内差异之间的相似性、差异和相互作用。 目标 3：使用从 MEC（乳腺、结肠）和 NHS（乳腺）前瞻性收集的生物样本，在巢式病例对照研究中测试这些身体脂肪量和分布的预测因子与癌症风险的关联。 目标 4：将结果与其他项目的结果整合，以便更好地了解基础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众健康。 这些数据将通过完善肥胖与癌症之间联系的风险估计来改善公众健康