A MULTILEVEL APPROACH TO ENERGY BALANCE AND CANCER ACROSS THE LIFECOURSE

项目总结(见说明)： 借助圣路易斯华盛顿大学教师以及其他机构的合作者和顾问的广泛科学专业知识，我们建议在现有跨学科方法的基础上，创建一个中心，从细胞到社会，研究肥胖和癌症的机制。我们包括的项目超越了传统的风险因素-癌症关联，着眼于多层次和多代人的关联以及传统癌症风险行为的相互作用。我们利用密苏里州提供的独特机会来研究人类人口，因为它具有跨种族和民族的多样性 社会经济地位。我们将描述先入为主的饮食、营养和建筑环境政策影响不活动、体力活动和能量平衡的机制，从而在整个生命过程中影响体重和癌症的发生。具体来说，我们的目标是： 1.以小鼠为模型，研究母鼠高脂饮食和代谢生物能量学变化对雄性小鼠前列腺癌易感性和前列腺发育的影响； 2.研究体力活动和肥胖对前列腺摘除术后排尿和性功能的影响； 3.以非霍奇金淋巴瘤为初始平台，建立包含生物、临床和社会风险和死亡率决定因素的跨生命周期和世代肥胖的模型，该模型可应用于不同的癌症结局； 4.研究影响能量平衡和肥胖的营养和建筑环境政策； 5.在跨学科的环境中培养博士后研究员，从事能量学和癌症方面的职业，并让我们大学的学者接触肥胖症和癌症的跨学科工作； 6.通过以中心的主题和资源为基础的较小规模的创新跨学科研究，促进科学协同作用；以及 7.通过建立一个卓越的跨学科中心，在卓越的行政、预算和技术资源的支持下，最大限度地提高TREC相关研究和核心的效率和生产率。 为了实现这些目标，我们提出了四个研究项目和五个核心，形成了一个具有凝聚力的、 跨学科中心专注于研究、培训/职业发展和传播。

PROJECT SUMMARY (See instructions): Drawing on the broad scientific expertise of faculty at Washington University in St. Louis and collaborators and consultants from other institutions, we propose to build on existing transdisciplinary approaches and create a center to address mechanisms of obesity and cancer, "from cell to society". We include projects that move beyond traditional risk factor-cancer associations to look at multilevel and multigenerational associations as well as the interaction of traditional cancer risk behaviors. We leverage the unique opportunity Missouri provides to study human populations given its diversity across race/ethnicity and socioeconomic status. We will delineate mechanisms by which preconception diet, nutrition & built environment polices impact inactivity and physical activity and energy balance to influence body weight and carcinogenesis across the life course. Specifically we aim to: 1. Investigate in a mouse model the effect of maternal high fat diet and changes in metabolic bioenergetics on prostate gland development and susceptibility to prostate cancer in male mouse offspring; 2. Study the role of physical activity and obesity in post-prostatectomy urinary and sexual function; 3. Develop models of obesity across the life course and generations incorporating biologic, clinical and social determinants of risk and mortality, which can be applied to different cancer outcomes, using non-Hodgkin Lymphoma as the initial platform; 4. Study policies relating to nutrition and built environment that impact energy balance and obesity; 5. Train postdoctoral fellows in a transdisciplinary environment to pursue careers in energetics and cancer and expose scholars from across our university to transdisciplinary work in obesity and cancer; 6. Foster scientific synergy via smaller-scale innovative transdisciplinary research that builds on the Center's theme and resources; and 7. Maximize efficiency and productivity of TREC-related studies and cores by building an outstanding transdisciplinary center supported by outstanding administrative, budgetary, and technology resources. To address these aims, we propose four research projects and five cores that form a cohesive, transdisciplinary center focused on research, training/career development, and dissemination.