Integrative Approach to Understand the Role of Diet, Physical Activity and Adiposity on Survival in Patients with Colorectal, Endometrial and Prostate Cancer

项目总结/摘要 肥胖被公认为是癌症发展和进展的一个强有力的危险因素， 通过各种促进生长的激素和炎症。虽然肥胖的体重管理是 通常受到临床指南的鼓励，体重控制通常特别令人沮丧，甚至 积极性很高的癌症患者。此外，与生存率低相关的意外体重减轻， 在癌症患者中可能是有问题的（“肥胖悖论”）。因此，关注饮食模式和身体 活动而不是减肥可能是一种更可行的方法，以防止或减少肥胖相关的 癌症患者的致癌介质。然而，目前对饮食和 身体活动在癌症生存中的作用不足以为癌症提供基于证据的建议 患者基于我们新的综合框架，我们假设低促炎/高胰岛素血症 癌症诊断后的饮食和高体力活动可能会降低全因死亡率和癌症特异性死亡率， 患有主要肥胖相关癌症的患者，包括结肠直肠癌、子宫内膜癌和前列腺癌。目标1将 检查诊断后促炎/高胰岛素血症饮食与癌症存活率的关系， 与肥胖和体重变化无关。我们将使用经验定义的两种饮食模式， 最近开发和验证的基础上，他们的预测炎症和胰岛素标志物在3个大的 同伙目标2将进一步建立在新出现的证据上，即诊断后的潜在有益效果 通过检查身体活动的重要方面（体积，类型和 强度）与癌症存活率相关，与肥胖和体重变化无关。目标3将审查 促炎/高胰岛素血症饮食和体力活动对癌症生存率的联合作用， 根据肥胖和体重变化独立分层，以更好地了解潜在的相互作用 饮食和体力活动之间的联系以及肥胖在其中的作用。为了实现这些目标，我们将 利用美国两项大型前瞻性队列研究（护士健康研究和 卫生专业人员随访研究），这是世界上为数不多的收集了这两种数据的队列之一 诊断前后的数据。总之，拟议的研究具有提供独特见解的巨大潜力 促炎/高胰岛素血症饮食、体力活动和肥胖在生存中的综合作用 肥胖相关癌症患者中。这项研究将成为一个有希望的一步， 制定临床可行的策略，以提高未来的癌症生存率，促进研究， 评估促炎/高胰岛素血症饮食和体力活动的影响，并产生新的 为癌症生存提供体重和生活方式指南的证据。

Project Summary/Abstract Obesity is well-recognized to be a strong risk factor for cancer development and progression, likely acting through various growth-enhancing hormones and inflammation. Although weight management of obesity is generally encouraged by clinical guidelines, weight control can be particularly frustrating in general, and even for highly motivated cancer patients. Further, unintentional weight loss, which is associated with poor survival, could be problematic in cancer patients (`obesity paradox'). Therefore, focusing on dietary pattern and physical activity instead of weight loss may be a more feasible approach to prevent or minimize the obesity-associated mediators of carcinogenesis for cancer patients. However, the current understanding on the role of diet and physical activity in cancer survival is insufficient to provide evidence-based recommendations for cancer patients. Based on our new integrative framework, we hypothesize that low pro-inflammatory/hyperinsulinemic diets and high physical activity after cancer diagnosis may reduce all-cause and cancer-specific mortality in patients with major obesity-related cancers, including colorectal, endometrial and prostate cancer. Aim 1 will examine the association of postdiagnosis pro-inflammatory/hyperinsulinemic diets with cancer survival, independent of adiposity and weight change. We will use empirically defined two dietary patterns that we recently developed and validated based on their prediction of inflammatory and insulin markers in 3 large cohorts. Aim 2 will further build on emerging evidence on the potential beneficial effect of postdiagnosis physical activity on cancer survival by examining the important aspects of physical activity (volume, type and intensity) in relation to cancer survival, independent of adiposity and weight change. Aim 3 will examine the combined association of pro-inflammatory/hyperinsulinemic diets and physical activity on cancer survival, both independently and stratified by adiposity and weight change, to better understand the potential interaction between diet and physical activity and the role of adiposity in the association. To complete these aims, we will utilize the considerable resources from two large US prospective cohort studies (Nurses' Health Study and Health Professionals Follow-up Study), which are among the few cohorts worldwide that have collected both pre-and post-diagnosis data. In summary, the proposed study has great potential to provide unique insights into the integrative role of pro-inflammatory/hyperinsulinemic diets, physical activity and adiposity in survival among patients with major obesity-related cancers. This study will serve as a promising step towards development of clinically feasible strategies to improve future cancer survival, facilitate research directed to assessing the effect of pro-inflammatory/hyperinsulinemic diets and physical activity, and generate new evidence to inform weight and lifestyle guidelines for cancer survival.