Pathways of Carcinogenesis Are Reflected in Patterns of Polyp Pathology in Patients Screened for Colorectal Cancer

BACKGROUND: There are multiple genetic routes to colorectal cancer, including chromosomal instability, mismatch repair dysfunction, and global hypermethylation. Few consider the possibility that multiple pathways are synchronously active. OBJECTIVE: This study was conducted to test the hypothesis that multiple synchronous carcinogenic pathways would result in an enhanced neoplastic phenotype. SETTING: This study took place during outpatient screening colonoscopy. PATIENTS: Patient were included who were undergoing colonoscopies for average and familial risk for colorectal cancer. DESIGN: Adenomas were evidence of chromosomal instability or DNA mismatch repair dysfunction, and serrated polyps of CpG island hypermethylation. Patients with 1 or 2 polyps were compared with those with >2 polyps, with polyps more than 10-mm diameter (advanced) as the end point. RESULTS: There were 1408 patients: 524 at average risk (41%) and 884 (59%) with a family history. Polyps were found in 47.7% of the average-risk patients and in 45.9% of patients with a family history. Adenoma detection rates were 33.8% and 30.4%, and serrated polyp detection rates were 24.8% and 23.9%. There were more advanced polyps in all patients with >2 polyps than in those with 1 or 2 (36.2% vs 13.6%, P < .002), as well as in the subgroup of patients having average-risk screening (50% vs 11.1%, P < .001). Having a combination of >2 adenomas and serrated polyps in the same colon increased the risk of finding advanced polyps compared with adenomas or serrated polyps alone (serrated polyps, 12.7%; >2 adenomas, 17.7%; both, 27.1%; P = .02). LIMITATIONS: Serrated polyps were not subclassified by histology. CONCLUSION: Coexistence of serrated and adenomatous polyps reflects a colon prone to advanced polyps, and potentially cancer.