Diet Composition, Weight Control and Breast Carcinogenesis

描述（由申请人提供）：本研究旨在回答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，除了预期的脂肪减少对循环生物可利用性类固醇水平的影响外，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, tnf - α）。

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.