PROJECT SUMMARY The goal of the Metabolic Dysregulation and Cancer Risk Consortium (MDCRC) is to identify tangible mechanistic/etiologic pathways that link obesity-related metabolic dysregulation with cancer risk to inform cancer prevention strategies. The Consortium proposes to accomplish this through developing common measures for obesity-related metabolic dysregulation for different cancer types, understanding how obesity- related metabolic dysregulation affects cancer initiation and development, characterizing signal cross-talk between key biologic processes that impact obesity-associated metabolic dysregulation and cancer risk, and determining the utility of emerging approaches for the discovery of novel obesity-associated metabolic targets in cancer risk and prevention. The Biostatistics Center (Center) in the Milken Institute School of Public Health (SPH) of the George Washington University (GW), the participating institution, proposes to serve as the MDCRC Coordinating Center (CC). The MDCRC CC will integrate this expertise and experience, drawing upon our successful history of coordinating center leadership in collaborative research consortia, capacity for innovation, and the extensive scientific expertise in obesity and cancer prevention, nutrition, exercise, metabolism, body composition, and bioinformatics/computational biology to form a CC that is rooted in scientific rigor and is flexible and responsive to the diverse challenges and scientific opportunities of the MDCRC. The specific aims of the MDCRC include to 1) provide scientific leadership and project management for collaborative cross-Consortium activities, including providing guidance on the selection of common measures and development of consistent protocols and manuals of operations, maintain private and public websites, establishing topical work groups, and spearhead outreach activities; 2) facilitate data harmonization, data sharing and results dissemination across the MDCRC sites and with NCI, including identification of opportunities for novel data collection to enrich the MDCRC data resources, developing a common data management platform, and training for site staff; and 3) establish a Self-Evaluation Core to promote timely self- evaluation, along with effective self-correcting actions, working with NCI and the Consortium investigators to establish criteria and outputs related to the “success” of individual investigators, study teams, and Consortium sites.

PROJECT NARRATIVE The Metabolic Dysregulation and Cancer Risk Consortium (MDCRC) is being created to study the biologic mechanisms by which obesity increases the risk of cancer in humans and will bring together several research groups studying how obesity alters normal metabolic pathways leading to cancer risk. The Consortium members will work together to identify common areas of data collection, and develop of a harmonized data set to accelerate research and discovery. The MDCRC Coordinating Center will facilitate the creation of this rich research data set, as well as provide both scientific leadership and project management for the collaborative cross-Consortium activities.