Molecular Basis of Young Onset Colorectal Cancer

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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 learn the skills necessary to conduct high-quality colerectal cancer prevention and control research. My proposed plan is targeted toward expanding our basic understanding of the molecular mechanisms underlying colerectal carcinogenesis, specifically within the young onset population. I plan to collect and characterize the tumors of 200 participants with young onset (less than 50 years of age) colerectal cancer (CRC) and 200 participants with older onset CRC. This particular segment of the CRC burden is not well understood with the exception that 15 to 30 percent of these young onset cases are known to be caused by defective DNA mismatch repair, having the molecular phenotype of microsatellite instability Msi(H). I propose to evaluate those young onset tumors that are microsatellite stable(MSS) with the same technique that successfully established the ground work for the discovery of at least three major tumor suppressor genes (p53, DCC, and APC) in CRC. Family history, epidemiological and clinical data will be collected and this cohort of participants will be followed longitudinally in order to determine outcome. These clinical data will be correlated with the results of the molecular information ascertained from the tumors of both the young and older onset cases, in order to develop useful algoritluns for patient management and to detect genetic events that may influence prognostication, early detection and prevention as well as treatment strategies. 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 cancer prevention research (including the responsible conduct of research). Following achievement of these goals, I am confident that I will be ready to continue my career as a successful independent investigator committed to colerectal cancer prevention and control.