PROJECT SUMMARY – MOLECULAR CARCINOGENESIS AND CHEMOPREVENTION (MCC) The Molecular Carcinogenesis and Chemoprevention (MCC) Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by Steven Clinton, MD, PhD, and Richard Fishel, PhD, has 48 members from 22 Departments and 8 OSU Colleges (Arts and Sciences, Dentistry, Education and Human Ecology, Food, Agriculture and Environmental Science, Medicine, Pharmacy, Public Health, and Veterinary Medicine). The MCC Program examines cancer as an integrated and dynamic process over time, with a major focus on the interface between genetics and the environment that collectively impacts the carcinogenesis cascade. This approach provides a foundation for chemoprevention and dietary interventions to reduce the burden of cancer in high-risk individuals as well as to decrease the incidence, mortality and morbidity of cancer in our Ohio catchment area (CA) and the nation. Our expertise extends to defining standards for genetic screening and counselling as well defining dietary and nutritional guidelines that impact cancer risk through public policy, nationally and globally. The Specific Aims of the MCC Program are: 1) Carcinogenesis: To characterize the genetic, molecular and cellular changes induced by germline, chemical, physical, hormonal or microbiological mediators that contribute to neoplastic transformation and multistage carcinogenesis; 2) Chemoprevention: To develop and characterize novel cancer chemopreventive agents and define their efficacy, safety, and mechanisms of action using biochemical, cellular and preclinical models that ultimately lead to early phase human studies; and, 3) Diet, Nutrition and Metabolism: To identify dietary patterns, nutritional components, and lifestyle variables that enhance or inhibit the carcinogenesis cascade across the continuum of cancer progression. MCC Program members published 547 cancer-relevant manuscripts between 12/01/14 and 11/30/19. Of these, 14% were intra- programmatic (multiple authors from MCC Program), 31% were inter-programmatic (authors from multiple OSUCCC Programs), and 72% were multi-institutional (authors from both CC and another institution). The total collaborative publications is 83%. MCC Program funding stands at $7.9M in overall direct, cancer-focused funding, of which $7.0M is peer-reviewed, including $6.8M direct funding from NIH ($3.4M from NCI). Over the last five years, MCC Program members have accrued 1,487 participants to trials; 670 to interventional trials and 817 to non-interventional trials. MCC members serve as leaders of the Ohio Colorectal Cancer Prevention Initiative involving 3,651 participants (3,310 colorectal and 341 endometrial) and ORIEN Total Cancer Care with enrollment of 50,683.The MCC program is fully integrated with the high priority crosscutting research initiatives of the OSUCCC and future plans complement and enhance programmatic aims while promoting interactions with the other research Program...