Diet Composition, Weight Control and Breast Carcinogenesis

饮食结构、体重控制和乳腺癌发生

• 批准号: 8100277
• 负责人: Henry J Thompson
• 金额: $ 27.09万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100277
• 关键词: Adjuvant Therapy; Affect; American Society of Clinical Oncology; Bioavailable; Biological; Biological Markers; Body Weight decreased; Body fat; Body mass index; Breast; C-reactive protein; Cancer Prognosis; Carbohydrates; Chronic; Clinical; Clinical Research; Control Groups; Data; Deoxyguanosine; Devices; Diet; Diet Modification; Energy Metabolism; Equilibrium; Estradiol; Estrone; Family; Fatty acid glycerol esters; Gonadal Steroid Hormones; Guidelines; Hormonal; Hormones; Inflammation; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Interleukin-6; Intervention Studies; Leptin; Masks; Measurement; Measures; Metabolic; Metabolism; Modeling; Obesity; Oncologist; Overweight; Participant; Patients; Pattern; Physical Examination; Physical activity; Plasma; Postmenopause; Prevention program; Process; Proteins; Protocols documentation; Publishing; Randomized; Recording of previous events; Resected; Rest; Risk; Schedule; Serum; Sex Hormone-Binding Globulin; Shapes; Staging; Tumor Necrosis Factor-alpha; Visit; Weight maintenance regimen; Woman; Work; adipokines; adiponectin; arm; blood glucose regulation; cancer prevention; cancer recurrence; carcinogenesis; design; energy balance; expectation; follow-up; ghrelin; glucose metabolism; group intervention; human TNF protein; interest; isoprostaglandin F2alpha type-III; malignant breast neoplasm; ornish diet; oxidation; programs; repaired; response; steroid hormone metabolism; steroid metabolism; tumor; tumor progression

DESCRIPTION (provided by applicant): This study is designed to answer questions about how dietary glycemic load and fat loss influence metabolic and hormonal processes that may affect breast cancer recurrence. We hypothesize that in addition to the anticipated effects of fat loss on circulating levels of bioavailable sex steroids, that the effects of excess fat on breast cancer prognosis can be attributed to three interrelated metabolic processes: altered glucose metabolism (IGF-1, IGFBP-3, glycated proteins), chronic inflammation (C-reactive protein, IL-6, TNF-alpha) and excessive cellular oxidation (8-hydroxy-2-deoxyguanosine and 8-isoprostane F-2 alpha). A 6 month intervention study involving 370 post menopausal women who have been treated for breast cancer is proposed. Randomized women, stratified by resected stage, systemic adjuvant therapy and body mass index (>25 and <35), will serve as either a non-intervention control group or will follow a tailored diet-physical activity program designed to create a weekly negative energy balance equivalent to 3500 kcal. The intervention groups will receive the same physical activity protocol, but one of two diets that differ in glycemic load. The specific aims are: Aim 1. Does dietary glycemic load alter the pattern of change observed in circulating factors involved in glucose homeostasis, chronic inflammation, cellular oxidation, and steroid hormone metabolism during progressive loss of body fat? We will also examine how observed changes in these circulating factors related to changes indicators of breast cancer recurrence. Aim 2. Do circulating factors associated with glucose homeostasis, chronic inflammation, and cellular oxidation display the same pattern of change in response to progressive fat loss as circulating analytes associated with sex steroid metabolism? Analytes of interest will be measured monthly throughout the study. Aim 3. Does dietary glycemic load affect the magnitude or rate of fat loss? Plasma adipokines such as leptin and adiponectin and plasma ghrelin will be measured to provide biological determinants that may help explain differences in response. The work proposed in this application should provide quantitative data about the importance of the magnitude of fat loss on metabolic and hormonal processes involved in cancer recurrence and provide guidance about effective dietary approaches that maximize weight loss benefits on breast cancer prognosis.

描述（由申请人提供）：本研究旨在回答有关饮食血糖负荷和脂肪减少如何影响可能影响乳腺癌复发的代谢和激素过程的问题。我们假设，除了脂肪减少对生物可利用性类固醇循环水平的预期影响外，过量脂肪对乳腺癌预后的影响还可归因于三个相互关联的代谢过程：葡萄糖代谢改变（IGF-1、IGFBP-3、糖化蛋白）、慢性炎症（C-反应蛋白、IL-6、 肿瘤坏死因子-α) 和过度细胞氧化（8-羟基-2-脱氧鸟苷和8-异前列腺素F-2α）。建议开展一项为期 6 个月的干预研究，涉及 370 名接受过乳腺癌治疗的绝经后妇女。按切除阶段、全身辅助治疗和体重指数（>25 和 <35）进行分层的随机女性将作为非干预对照组，或遵循量身定制的饮食-身体活动计划，旨在创造相当于 3500 kcal 的每周负能量平衡。干预组将接受相同的身体活动方案，但采用血糖负荷不同的两种饮食之一。具体目标是： 目标 1. 在体脂逐渐减少过程中，饮食血糖负荷是否会改变参与葡萄糖稳态、慢性炎症、细胞氧化和类固醇激素代谢的循环因子的变化模式？我们还将研究观察到的这些循环因子的变化如何与乳腺癌复发指标的变化相关。目标 2. 与葡萄糖稳态、慢性炎症和细胞氧化相关的循环因子是否与与性类固醇代谢相关的循环分析物一样，在逐渐减脂的反应中表现出相同的变化模式？在整个研究过程中，每月都会测量感兴趣的分析物。目标 3. 膳食血糖负荷是否会影响脂肪减少的幅度或速度？将测量血浆脂肪因子，例如瘦素和脂联素以及血浆生长素释放肽，以提供可能有助于解释反应差异的生物决定因素。本申请中提出的工作应提供有关脂肪减少程度对癌症复发所涉及的代谢和激素过程的重要性的定量数据，并提供有关有效饮食方法的指导，以最大限度地提高减肥对乳腺癌预后的益处。

项目成果

Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors.

• DOI: 10.3390/nu7075156
• 发表时间: 2015-06-26
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Thompson HJ;Sedlacek SM;Wolfe P;Paul D;Lakoski SG;Playdon MC;McGinley JN;Matthews SB
• 通讯作者: Matthews SB