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

描述（由申请人提供）：疲劳是癌症幸存者中最常见的治疗后问题，影响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会带来相当大的压力，压力和抑郁可以直接促进促炎细胞因子的产生。饮食也会影响炎症;在美国人口中，总能量摄入的大约三分之一来自通常饱和脂肪含量高的快餐消费，并且最近在高饱和脂肪的膳食之后增强的炎症的证明已经引起了对餐后炎症作为慢性炎症的驱动因素的可能性的兴趣。当高脂肪、快餐型的膳食充斥着简单的碳水化合物和甘油三酯时，这些膳食也会引发IL-6和CRP的峰值。此外，由快餐类食物引起的促炎反应被肥胖夸大，高脂肪食物将肥胖的特征性炎症反应推得更高并持续更长时间。肥胖和炎症都与乳腺癌幸存者的预后较差有关。基于我们现有的前瞻性癌症疲劳研究（R 01 CA 131029，Kiecolt-Glaser PI），该双盲，一项随机交叉试验将评估快餐类食物后炎症变化与疲劳之间的关系（高饱和脂肪）相比，乳腺癌幸存者和良性对照组（乳腺癌初始检查异常的女性）的脂肪水平（中等水平）。膳食挑战还提供了一种新的安全方法来评估与对照组相比，炎症短暂增加对幸存者情绪和疲劳的影响。具体目标：（1）描述快餐型膳食与健康膳食相比对乳腺癌幸存者和良性对照的餐后炎症反应的影响，并评估中枢性肥胖和抑郁症状作为炎症和疲劳预测因子的相对影响;以及（2）以评估与幸存者持续疲劳相关的炎症网络的过度激活是否可能部分由饮食引起。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跟踪的女性亚组中，我们利用我们的良好特征样本以最小的成本解决重要的公共卫生问题。在我们的纵向项目中收集的随访样本将提供评估膳食挑战后炎症和疲劳增加与更大炎症和疲劳的前瞻性相关程度的方法。因此，这个R21使用一种新的范式来评估乳腺癌幸存者和良性对照组中饮食、疲劳、抑郁症状、肥胖和炎症之间的横截面和纵向的机械联系。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。 公共卫生相关性：炎症与乳腺癌幸存者的疲劳以及许多与年龄有关的疾病有关。使用我们前瞻性观察研究中的乳腺癌幸存者和良性对照，我们将评估与癌症幸存者和对照组的健康膳食相比，快餐型膳食（饱和脂肪含量高）后炎症如何增加，我们将评估肥胖，抑郁和膳食类型的相对贡献作为炎症和疲劳的预测因子横截面以及纵向。

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.