title: Pathways of carcinogenesis are reflected in patterns of polyp pathology in patients screened for colorectal cancer.
abstract: 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.
  
  
  METHODS
  This study took place during outpatient screening colonoscopy.
  
  
  METHODS
  Patient were included who were undergoing colonoscopies for average and familial risk for colorectal cancer.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Serrated polyps were not subclassified by histology.
  
  
  CONCLUSIONS
  Coexistence of serrated and adenomatous polyps reflects a colon prone to advanced polyps, and potentially cancer.
authors: Department of Colorectal Surgery, Digestive Diseases Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors: Megan
authors: M
authors: Costedio
authors: James
authors: J
authors: Church
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D043171:Chromosomal Instability / Q000235:genetics; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D012307:Risk Factors