Insulin, the IGF Axis, and Colorectal Neoplasia

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DESCRIPTION (provided by applicant): The Cancer Prevention, Control, and Population Sciences Career Development Award will provide an excellent opportunity for me to acquire and refine the skills necessary to conduct high-quality gastrointestinal cancer prevention research at a population level. My proposed research plan involves the rigorous evaluation of a timely central hypothesis with direct relevance to colorectal cancer prevention. Using a series of different general, molecular, and genetic epidemiologic approaches, I intend to explore unresolved or unexamined issues related to the possibility that hyperinsulinemia, either alone or in combination with insulin-like growth factor (IGF) axis proteins, is causally linked to colorectal carcinogenesis. Existing data from cell culture experiments, animal model systems, and human observational studies support this hypothesis, yet many essential questions remain to be addressed. In the context of mentored research, I plan to perform (1) a historical cohort study of type 2 diabetes mellitus (DM) and colorectal adenocarcinoma risk, (2) a case-control study of type 2 DM and colorectal adenoma risk, (3) a nested case-control study of serum insulin/IGF axis protein concentrations and colorectal adenocarcinoma risk, (4) a pilot study of IGF axis mRNA expression levels in neoplastic versus non-neoplastic colorectal mucosa, and (5) a prospective cohort study of IGF axis gene polymorphisms among subjects with or without colorectal neoplasia. These studies should provide meaningful scientific data, while simultaneously affording me a broad exposure to and considerable experience with several important investigational tools. To further enhance my career development, I plan to obtain didactic training in areas relevant to gastrointestinal cancer prevention research (including the responsible conduct of research). Additionally, I intend to serve as an instructor for a cancer epidemiology course at Mayo Graduate School. The resources of my sponsoring institution are excellent and will facilitate the successful, efficient completion of my overall objectives. Following achievement of these goals, I am confident that I will be ready to continue my career as a successful independent investigator committed to academic research.