Fast Food, Depression, Obesity, and Inflammation in Breast Cancer Survivors

描述（由申请人提供）：疲劳是癌症幸存者治疗后最常见的问题，影响了三分之一或更多的长期幸存者。幸存者的持续疲劳可能部分与继发于癌症及其治疗的炎症网络的过度激活有关。此外，癌症诊断和癌症治疗可能相当紧张，压力和抑郁会直接增加促炎细胞因子的产生。饮食也会影响炎症；美国人大约三分之一的总能量摄入来自饱和脂肪含量高的快餐，最近有证据表明，在摄入高饱和脂肪的食物后，炎症会加剧，这引发了人们对餐后炎症可能是慢性炎症的驱动因素的兴趣。当高脂肪、快餐类的食物充斥着简单的碳水化合物和甘油三酯时，这些食物也会引发IL-6和CRP的飙升。此外，快餐类食物引起的促炎反应被肥胖夸大了，而高脂肪的食物使肥胖特有的炎症反应升高得更高，持续的时间更长。肥胖和炎症都与乳腺癌幸存者较差的预后有关。在我们现有的前瞻性癌症疲劳研究（R01 CA131029, Kiecolt-Glaser PI）的基础上，这项双盲、随机交叉试验将评估乳腺癌幸存者和良性对照（乳腺癌初始检测异常的女性）在食用快餐（高饱和脂肪）和健康饮食（中等脂肪水平）后炎症和疲劳变化之间的关系。与对照组相比，饮食挑战也提供了一种新颖而安全的方法来评估幸存者短暂的炎症增加对情绪和疲劳的影响。具体目的：(1)表征与健康膳食相比，快餐型膳食对乳腺癌幸存者和良性对照餐后炎症反应的影响，并评估中央性肥胖和抑郁症状作为炎症和疲劳预测因子的相对影响；(2)评估是否炎症网络的过度激活似乎与幸存者的持续疲劳有关，可能部分是由饮食引起的。通过将这些额外的评估添加到我们正在进行的研究中已经被跟踪的妇女亚组中，我们利用我们的特征良好的样本以最小的成本解决一个重要的公共卫生问题。在我们的纵向项目中收集的后续样本将提供评估饮食挑战后炎症和疲劳增加的程度与未来更严重的炎症和疲劳相关的方法。因此，本R21使用了一种新的范式来评估乳腺癌幸存者和良性对照中饮食、疲劳、抑郁症状、肥胖和炎症之间的横断面和纵向机制联系。这些数据将促进人们更好地理解饮食、抑郁和肥胖相互作用引发炎症的方式。

DESCRIPTION (provided by applicant): Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long- term survivors. Persistent fatigue in survivors may be related in part to overactivation of the inflammatory network secondary to cancer and its treatment. Furthermore, a cancer diagnosis and cancer treatments can be quite stressful, and stress and depression can directly enhance the production of proinflammatory cytokines. Diet also impacts inflammation; about one-third of the total energy intake in the United States population comes from fast food consumption that is typically high in saturated fat, and recent demonstrations of enhanced inflammation following meals high in saturated fats have sparked interest in the possibility that postprandial inflammation acts as a driver for chronic inflammation. When high-fat, fast-food-type meals flood the body with simple carbohydrates and triglycerides, the meals also trigger spikes in IL-6 and CRP. Furthermore, the proinflammatory responses that are provoked by fast-food-type meals are exaggerated by obesity, and high-fat meals push obesity's characteristic elevated inflammatory responses even higher and sustain them longer. Both obesity and inflammation are associated with a poorer prognosis in breast cancer survivors. Building on our existing prospective cancer fatigue study (R01 CA131029, Kiecolt-Glaser PI), this double-blind, randomized crossover trial will assess the association between changes in inflammation and fatigue following a fast-food-type meal (high in saturated fat) compared to a healthier meal (moderate level of fats) in breast cancer survivors and benign controls (women who had an initial abnormal test for breast cancer). The meal challenge also provides a novel and safe method to assess the impact of a transient increase in inflammation on mood and fatigue in survivors compared to controls. Specific aims: (1) To characterize the impact of a fast-food-type meal compared to a healthier meal on postprandial inflammatory responses in breast cancer survivors and benign controls, and to appraise the relative impacts of central adiposity and depressive symptoms as predictors of inflammation and fatigue; and (2) to assess whether the overactivation of the inflammatory network that appears to be related to persistent fatigue in survivors may be fueled in part by diet. By adding these additional assessments to a subgroup of women who are already being followed within our ongoing study, we leverage our well-characterized sample to address an important public health question at minimal cost. The follow-up samples collected in our longitudinal project will provide the means to assess the extent to which increases in inflammation and fatigue following a meal challenge are associated with greater inflammation and fatigue prospectively. Thus, this R21 uses a novel paradigm to assess mechanistic connections among diet, fatigue, depressive symptoms, obesity, and inflammation both cross-sectionally and longitudinally in breast cancer survivors and benign controls. The data will promote a better understanding of the ways that diet, depression, and obesity interact to kindle inflammation. PUBLIC HEALTH RELEVANCE: Inflammation is associated fatigue in breast cancer survivors, as well as with many age-related diseases. Using breast cancer survivors and benign controls from our prospective observational study, we will assess how inflammation increases following a fast-food-type meal (high in saturated fat) compared to a healthy meal in cancer survivors and controls, and we will evaluate the relative contributions of obesity, depression, and meal type as predictors of inflammation and fatigue both cross-sectionally as well as longitudinally.