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 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 conducted 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 provided us with approximately 2500 participants and allowed us to perform the largest epidemiological study of this kind to date. In addition, we had 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 required 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 and project, Dr. David Alberts, and cosponsors, Dr. Mark Haussler, Dr. Elena Martinez, and Dr. Sylvan Green provided expertise, guidance, and support for the successful completion of the proposed research along with the Arizona Cancer Center (ACC) at the University of Arizona. This project was funded by the National Institutes of Health.