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Project 2

SPORE Project 2: Detection of Advanced Colon Adenoma via Stool DNA (sDNA) Methylation Testing

Clinical PI: Gregory S. Cooper, MD
Basic PI: Li Li, MD, PhD

Testing for aberrant molecular/genetic markers in stool DNA (sDNA) is emerging as a promising alternative to colonoscopy, and multisociety guidelines currently endorse the use of sDNA testing in the early detection of colorectal cancer. A potentially more important target in screening is the advanced adenoma, which is found in 5-10% of an average risk screening population and has a higher likelihood of progression to colorectal cancer. However, data on the efficacy of sDNA testing for advanced adenomas, hence prevention of colorectal cancer, are limited. The goal of this project is to perform a population-based screening study to systematically evaluate the accuracy and clinical relevance of sDNA testing for advanced adenomas. Our goal is to recruit 1600 patients over a four-year period who are referred for screening colonoscopy. The patients will be recruited from hospital and community-based practices and will include a large African American population. We will collect demographic, dietary and anthropometric measures, stool for both DNA testing and fecal immunochemical testing, and colonoscopy and pathology results. In addition, patients with findings of positive sDNA and advanced adenomas will undergo repeat sDNA testing and colonoscopy at one year, and patients with persistently positive sDNA and a negative index colonoscopy will undergo repeat colonoscopy and upper endoscopy. This project is highly translational and information gained from this study may have significant and immediate implication for the clinical practice of screening and primary prevention of colorectal cancer, and surveillance of patients with advanced adenomas.

Specific Aims

Aim 1: Evaluate the performance characteristics of sDNA testing for the detection of advanced adenomas in an asymptomatic average-risk screening population.

Aim 2: Determine the concordance/discordance between tissue and stool methylation.

Aim 3: Investigate the persistence of positive sDNA testing after removal of advanced adenomas.

Aim 4: Assess the frequency of missed or occult colonic and upper gastrointestinal neoplasia in patients with initially normal colonoscopies and persistently positive sDNA testing.