Diet Composition, Weight Control and Breast Carcinogenesis

描述(申请人提供)：这项研究旨在回答有关饮食血糖负荷和脂肪减少如何影响代谢和荷尔蒙过程的问题，这些过程可能会影响乳腺癌的复发。我们假设，除了脂肪减少对循环中生物可利用的性类固醇水平的预期影响外，过量脂肪对乳腺癌预后的影响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) 细胞过度氧化(8-羟基-2-脱氧鸟苷和8-异前列腺素F-2α)。一项为期6个月的干预研究涉及370名接受乳腺癌治疗的绝经后妇女。根据切除分期、全身辅助治疗和体重指数(&gt；25和&lt；35)分层的随机女性，要么作为非干预对照组，要么遵循量身定制的饮食-体力活动计划，以创造相当于3500千卡的每周负能量平衡。干预组将接受相同的体力活动方案，但两种饮食中的一种血糖负荷不同。具体目标是：目的1.饮食血糖负荷是否改变了在进行性减脂过程中观察到的循环因子的变化模式，这些循环因子涉及葡萄糖稳态、慢性炎症、细胞氧化和类固醇激素代谢？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。目的2.与葡萄糖稳态、慢性炎症和细胞氧化相关的循环因子在进行性脂肪减少时是否表现出与与性激素代谢相关的循环分析物相同的变化模式？在整个研究过程中，将每月测量感兴趣的分析物。目的3.饮食中的血糖负荷是否影响脂肪减少的幅度或速度？将对瘦素和脂联素等血浆脂肪因子和血浆生长激素进行测量，以提供可能有助于解释反应差异的生物决定因素。这项申请中提出的工作应该提供关于脂肪损失的程度对癌症复发所涉及的代谢和荷尔蒙过程的重要性的定量数据，并为最大限度地减轻乳腺癌预后的有效饮食方法提供指导。

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.