) Most colorectal cancers arise from adenomatous polyps, and a large proportion of adenoma patients will develop new adenomas after their initial polypectomy. This application is to evaluate tumor markers in the initial adenomas as potential predictors of adenoma recurrence in 300 adenoma patients recruited as part of an existing NCI-funded follow-up study (RO1 CA72784). In addition to the markers (t)53 over-expression and mutation, K-ras mutation, and Ki-67 labeling index) evaluated in the parent study, we propose in this application to investigate the following biomarkers in relation to adenoma recurrence: the ratio of the degree of apoptosis to cellular proliferation, expression of the Bcl-2 family genes (bcl-2, bak, bax) and expression of thymidylate synthase (TS) gene. These biomarkers will be measured using immunohistochemical techniques. This newly proposed study is feasible and extremely cost-efficient, since patients for this study have already been recruited, follow-up information and tumor tissue samples needed for the proposed assays have already been collected, and laboratory methods for most biomarkers proposed in this study have already been established in our laboratory. The questions to be investigated in this application are important, and associations of these tumor markers with adenoma recurrence have not been reported. This study is likely to provide important information valuable for identifying high-risk subgroups of patients who need close follow-up and/or intervention to reduce their risk of colorectal cancer.
