Diet Composition and Genetics: Effects on Weight, Inflammation and Biomarkers

饮食成分和遗传学：对体重、炎症和生物标志物的影响

• 批准号: 8072502
• 负责人: CHERYL L ROCK
• 金额: $ 27.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-07 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072502
• 关键词: Address; Behavioral; Biological; Biological Markers; Body Weight decreased; Body mass index; Breast Cancer Prevention; Breast Cancer Risk Factor; C-reactive protein; Cancer Control; Carbohydrates; Cessation of life; Clinical Trials; Cognitive; Collection; Counseling; DNA Methylation; Data; Diabetes Mellitus; Diagnosis; Diet; Diet Modification; Dietary Practices; Energy Intake; Energy Metabolism; Estrogens; Fat-Restricted Diet; Fatty acid glycerol esters; Functional disorder; Future; Gene Expression; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Status; Gonadal Steroid Hormones; Guidelines; Health; Homeostasis; Hormonal; Hyperinsulinism; Immune system; Incidence; Individual; Inflammation; Insulin; Insulin Resistance; Intake; Interleukin-6; Knowledge; Link; Macronutrients Nutrition; Malignant Neoplasms; Metabolic; Methylation; MicroRNAs; Modeling; Nutrient; Obesity; Observational Study; Outcome; Pattern; Population Study; Postmenopause; Premenopause; Procedures; Production; RNA; Randomized; Randomized Controlled Trials; Recurrence; Relative (related person); Relative Risks; Risk; Risk Factors; Sampling; Sex Hormone-Binding Globulin; Tumor Necrosis Factor-alpha; Weight; Weight maintenance regimen; Woman; base; breast cancer diagnosis; cancer recurrence; cancer risk; cytokine; energy balance; gene interaction; genome-wide; inflammatory marker; malignant breast neoplasm; monounsaturated fat; mortality; novel strategies; programs; response; tumor progression; weight loss intervention

Excess adiposity is a risk factor for postmenopausal breast cancer and a major risk factor for recurrence in both pre- and postmenopausal breast cancer, and the biological mechanisms are not fully understood. Obesity is associated with elevated endogenous circulating estrogen as well as activation of the immune system, a key causative factor in insulin resistance and hyperinsulinemia. Optimal macronutrient distribution of weight loss diets has not been established. Cancer control guidelines have historically encouraged a lowfat diet, but current evidence does not suggest this strategy to be of particular benefit. Emerging evidence suggests that the optimal diet composition for weight loss may differ across individuals based on metabolic status and genetic factors. Effects of diet composition on hormonal and other factors linking obesity to breast cancer in weight loss interventions have not been compared or examined. The specific aims ofthis study are: (1) To examine whether there is a differential weight loss response to different dietary macronutrient composition in a weight loss intervention in healthy obese women, depending on insulin resistance status; (2). To examine whether there is a differential response (depending on insulin resistance status) to different dietary macronutrient composition in a weight loss intervention in the hormonal factors and markers of inflammation that may link obesity to breast cancer mortality (insulin, SHBG, estrogens, C-reactive protein, interleukin-6 [IL-6], tumor necrosis factor a [TNF-a], and as a marker for gene expression, IL-6 and TNF-a gene methylation); and (3) To identify nutrient-gene interactions that contribute to differential response of cytokines to weight loss and diet composition associated with polymorphisms in IL-6 and TNF-a genes. These aims will be addressed in a randomized controlled study involving 156 obese women randomly assigned to a high-carbohydrate (65% energy) low-fat (20% energy) or low-carbohydrate (45% energy) highmonounsaturated fat (35% energy) diet in a 12-month behavioral weight loss program. We hypothesize that greater weight loss and reduction in biomarkers will occur in insulin resistant women assigned to the lower carbohydrate, higher fat diet. We also hypothesize that the ability of weight loss and diet modification to decrease IL-6 and TNF-a concentrations will be influenced by polymorphisms in these genes. Results of this study will help to refine and individualize dietary guidance for optimal weight control and breast cancer prevention and will contribute to knowledge of mechanisms that link insulin resistance, inflammation and obesity to risk and progression of breast cancer.

过度肥胖是绝经后乳腺癌的危险因素，也是绝经前和绝经后乳腺癌复发的主要危险因素，并且尚不完全了解生物学机制。 肥胖与内源性循环雌激素以及免疫系统的激活有关，免疫系统是胰岛素抵抗和高胰岛素血症的关键原因。尚未确定减肥饮食的最佳大量营养素分布。从历史上看，癌症控制指南一直鼓励低脂饮食，但目前的证据并未暗示该策略特别有益。新兴的证据表明，根据代谢，个体的最佳减肥饮食组成可能会有所不同 状态和遗传因素。尚未比较或检查饮食组成对肥胖与乳腺癌关联的激素和其他因素的影响。这项研究的具体目的是：（1）检查健康肥胖女性的体重减轻干预措施中是否对不同饮食中的大量营养素组成有差异反应，具体取决于胰岛素抵抗状态； （2）。检查是否存在重量损失干预措施中不同饮食大量营养成分的反应（取决于胰岛素抵抗状态）在激素因素和炎症标志物中是否存在肥胖与乳腺癌死亡率与乳腺癌死亡率联系起来（胰岛素，SHBG，SHBG，雌激素，雌激素，C-反应蛋白，interleukin-6 [IL-6 [IL-6]，TULMOR NECRISS，TULLIS CAIM，基因表达的标记，IL-6和TNF-A 基因甲基化）； （3）确定营养基因的相互作用，这有助于细胞因子对与IL-6和TNF-A基因中多态性相关的体重减轻和饮食组成的差异反应。 这些目标将在一项随机对照研究中解决，其中涉及156名肥胖女性在12个月的行为减肥计划中随机分配给高碳水化合物（65％能量）低脂（20％能量）或低碳水化合物（45％能量）生日饱和脂肪（35％能量）。我们假设在分配给较低碳水化合物，更高脂肪饮食的胰岛素女性中，将发生更大的体重减轻和生物标志物的减少。我们还假设体重减轻和饮食修饰降低IL-6和TNF-A浓度的能力将受这些基因多态性的影响。这项研究的结果将有助于完善和个性化最佳体重控制和预防乳腺癌的饮食指南，并有助于了解将胰岛素抵抗，炎症和肥胖与乳腺癌的风险和进展联系起来的机制。