The objectives of this trial are as follows:
A. To determine the efficacy and safety of celecoxib versus placebo in preventing the occurrence of newly detected colorectal adenomas in subjects at increased risk for colorectal carcinoma. In addition to incidence, other established risk factors will be evaluated for their association with occurrence of new colorectal adenomas, including cancer family history and adenoma size, histopathologic grade, multiplicity and location. Primary assessment of treatment efficacy will be the reduction in the number of subjects with adenomas at colonoscopy after Year 1 and Year 3 of study drug use. Secondary assessments of treatment efficacy will be 1) the number of adenomas 2) the histopathologic grade of adenomas and 3) the size of adenomas, also measured after one year and three years of study drug use. These factors will be incorporated into a risk model for predicting adenoma occurrence and response to celecoxib.

B. To determine the efficacy of celecoxib versus placebo in modulating one or more of a panel of biomarkers for colorectal cancer at the cellular and molecular level sampled in a subset of subjects at selective sites at baseline and after Year 1 and Year 3 of study drug use. These biomarkers will include measurements of aberrant crypt foci (ACF), proliferation (index and crypt distribution), apoptosis (index and crypt distribution), COX expression and activity. If modulation of one or more mucosal biomarkers occur, we will explore whether it correlates with the development of incident colorectal neoplasia (adenomas/carcinomas), thereby attempting to validate the surrogacy of that biomarker.