Mechanisms of Energy Balance and Cancer Prevention

描述（由申请人提供）：这是一份竞争性续期申请（响应RFA-CA-10-006）“跨学科研究在能量学和癌症（U54）”。西雅图TREC中心的首要主题将是在小规模和人群水平的人体实验研究中确定能量平衡变化影响癌症发展和进展的机制。我们建议使用我们在TREC资助的前5年开发的跨学科方法，并利用我们在进行人类干预试验方面的优势，阐明连接癌症连续体中的能量平衡的新途径，从普通人群到高风险个体，再到癌症幸存者。项目1将在一项对照喂养研究中，调查热量限制加低糖负荷饮食与单独低糖负荷饮食在一系列综合终点中的作用：全身性胰岛素抵抗和炎症、脂肪组织炎症和肠道微生物群落。项目2将测试我们基于小组的糖尿病预防计划减肥干预与控制对乳腺癌幸存者预后相关生物标志物的影响，包括全身代谢和炎症标志物，乳腺吸痰细胞学，增殖和基因表达。项目3将在小型工作场所进行一项随机试验，评估多层次肥胖预防干预措施，其中干预措施将包括工作、家庭和社区组成部分。这3个项目的其他新工作将研究：减肥对蛋白质组学的影响，热量限制对芳香化酶脂肪表达的影响，肠道健康与全身胰岛素抵抗和炎症的交叉，以及体重减轻和维持中的生物行为相互作用。五个核心将支持所有项目：所需的管理，培训/教育和推广，以及发展，推荐的生物统计学/生物信息学，以及实验室核心。一个由跨学科研究人员组成的团队将跨项目合作，包括流行病学、肿瘤学、营养学、生物化学、内分泌学、生物统计学和行为科学方面的专家。教育/培训和推广计划将包括个人培训和项目经验，期刊俱乐部，研讨会，以及有关trec相关主题的国内和国际专题讨论会和会议。我们建议继续我们在跨trec中心合作方面的杰出记录，在那里我们领导了几项多中心发展研究。我们建议继续我们为TREC社区带来的强有力的领导，并继续我们在能量平衡和癌症领域的国际领导和贡献。

DESCRIPTION (provided by applicant): This is a competitive renewal application (in response to RFA-CA-10-006) "Transdisciplinary Research in Energetics and Cancer (U54)". The overarching theme of the Seattle TREC Center will be to determine mechanisms by which changes in energy balance influences cancer development and progression across the adult lifespan in small-scale and population-level human experimental studies. We propose to elucidate new pathways linking energy balance across the cancer continuum from the general population, to high risk individuals, to cancer survivors, using transdisciplinary methods that we developed in the first 5 years of TREC funding and capitalizing on our strengths in conducting human intervention trials. Project 1 will investigate, in a controlled feeding study, the role of caloric restriction plus a low glycemic load diet vs. low glycemic load diet alone in relation to an integrated set of endpoints: systemic insulin resistance and inflammation, adipose tissue inflammation and gut microbial community. Project 2 will test the effect of our group-based modification of the Diabetes Prevention Program weight loss intervention vs. control on prognosis-related biomarkers in breast cancer survivors including systemic metabolic and inflammatory markers, and breast aspirate cytology, proliferation, and gene expression. Project 3 will conduct a randomized trial evaluating a multi-level obesity prevention intervention in small worksites, where the intervention will include work, home, and neighborhood components. Additional novel work in the 3 projects will examine: weight loss effects on proteomics, caloric restriction effects on adipose expression of aromatase, the intersection of gut health with systemic insulin resistance and inflammation, and biology behavior interactions in weight loss and maintenance. Five Cores will support all Projects: the required Administration, Training/Education & Outreach, and Developmental, the recommended Biostatistics/Bioinformatics, and a Laboratory Core. A team of transdisciplinary researchers will collaborate across projects, including experts in epidemiology, oncology, nutrition, biochemistry, endocrinology, biostatistics, and behavioral science. The education/training and outreach program will include individual trainee mentoring and project experience, journal club, seminars, and national and international symposia and meetings on TREC-related topics. We propose to continue our outstanding record of cross-TREC center collaborations, where we have led several multi-center developmental studies. We propose to continue the strong leadership we have brought to the TREC community, and to continue our international leadership and contributions to the field of energy balance and cancer.