The goal of this award is to build upon my experience in cancer and genetic epidemiology to develop an independent program of research in cancer epidemiology focusing on pancreatic cancer. A three-phase approach combining educational development and mentored research is proposed to achieve this goal. Phase 1 will expand my understanding of the biology and pathogenesis of pancreatic cancer through didactic work and mentored research in cohort and nested case-control studies of pancreatic cancer risk in relation to iron, HFE gene polymorphisms, and Vitamin C consumption. Additional cohort analyses of latitude, calcium, vitamin A, and vitamin D consumption will include sub-classification of pancreatic cancers based on p21 and p27 expression in tumor samples. This work will provide a framework of preliminary results to support future research proposal, and develop my understanding of pancreatic cancer biology as a foundation for developing and investigating novel hypotheses. In phase 2 I will develop advanced skills in mathematics and statistical theory through courses and mentored research will determine the role of cigarette smoking and other established risk factors for pancreatic cancer in initiation, proliferation, and transformation phases of pancreatic tumors by re-analyzing cohort data using an innovative hazard function analysis linked to a mathematical multi-step model of carcinogenesis. Moreover, the feasibility of applying analyses based on multi-step models of carcinogenesis to case-only studies of the age at diagnosis of cancer will be determined. Through phase 3 I will develop local data resources in support of future research proposals by working with clinical and basic science collaborators to expand the epidemiologic questionnaire module of an existing pancreatic cancer patient database. The planned educational development and mentored research in this proposal will expand my understanding of pancreatic cancer biology, develop competency in developing novel methods, and provide essential data resources in support of a career in cancer research.