Genetic and Epigenetic Markers for Colorectal Adenoma Recurrence

Vanderbilt University, Nashville TN

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Abstract

Most colorectal cancers arise from adenomatous polyps, and a large proportion of adenoma patients develop new (metachronous) adenomas after their initial polypectomy. There is considerable controversy regarding an appropriate surveillance interval for adenoma patients after removal of their initial adenomas. We propose to conduct a follow-up study to evaluate both genetic susceptibility risk variants and tumor markers in relation to the risk of metachronous adenomas. The proposed study will be conducted in approximately 1,500 patients diagnosed with either multiple adenomas or a pathologically advanced adenoma. These patients have already been recruited in our previous studies. In addition to clinical and epidemiologic data, we have already obtained germline DNA samples, fresh-frozen polyp tissues, and formalin-fixed, paraffin-embedded (FFPE) from a large proportion of study participants. In this study, we propose to: 1) follow up with study participants to collect information related to follow-up exams and adenoma recurrence and to obtain FFPE blocks of initial adenomas from the remaining patients whose samples have not yet been collected 2) evaluate the association of genetic and epigenetic tumor markers with recurrent adenomas 3) evaluate the association of adenoma recurrence with GWAS-identified genetic variants 4) establish a risk-assessment model and evaluate the utility of genetic susceptibility and tumor markers alone and in combination with known predictors (such as pathologic features of initial adenomas) in predicting the risk of adenoma recurrence. This proposed study will provide critical information that is valuable to identify high-risk adenoma patients for intensive follow-up programs and chemoprevention.