My long-term professional goal is to apply methodology from several different disciplines, including epidemiology, nutrition, molecular biology, and statistics, to design and test hypotheses that make important contributions to translational cancer prevention research. Further training is required in order to achieve this goal, and the current proposal had been designed to both answer important research questions and to provide training in these areas. Epidemiological and laboratory research has shown that dietary intake of vitamin D and calcium may be associated with a decreased risk of colorectal neoplasia, and that polymorphisms of the vitamin D receptor (VDR) may also be associated with risk. In addition, it was recently reported that the potentially carcinogenic bile acid lithocholic acid (LCA) is a ligand for the VDR. The effects of LCA-VDR binding on colorectal neoplasia are unknown. Therefore, we propose to conduct a study to investigate whether VDR polymorphisms are associated with the risk of colorectal adenoma recurrence, and whether this association is modified by dietary intake of vitamin D, calcium, and fat. The combination of two study populations from separate nutrition intervention trials will provide us with approximately 2500 participants and allow us to perform the largest epidemiological study of this kind to date. In addition, we will have the ability to conduct experiments in molecular biology to test the functional role of the VDR in colorectal neoplasia, including the translational effects of VDR polymorphisms and LCA binding in colon cancer cell lines. Completion of these objectives will require thorough and detailed training in epidemiological design and analysis, statistical analyses of gene-nutrient interactions, and molecular approaches to laboratory experimentation. The sponsor for this proposal, Dr. David Alberts, and cosponsors, Dr. Mark Haussler, Dr. Elena Martinez, and Dr. Sylvan Green will each provide expertise, guidance, and support for the successful completion of the proposed research. The Arizona Cancer Center (ACC) at the University of Arizona has faculty from diverse backgrounds, excellent laboratory facilities, and provides an outstanding environment for development of a career in cancer prevention. The resources at the ACC, coursework, and practical experience will be combined in a program designed to assist me in pursuing a successful career in translational cancer prevention research.
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