MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps

Abstract Background & Aims: MYH -associated polyposis is a recently described disease that is characterized by multiple colorectal adenomas and a recessive pattern of inheritance. Individuals with MYH -associated polyposis have biallelic mutations in MYH, a base excision repair gene, and are negative for germline mutations in the APC gene. In this study, the 2 most prevalent MYH mutations in white persons, Y165C and G382D, were analyzed for their presence in 984 subjects selected from 3 groups: 400 undergoing screening colonoscopy and found to have 0–3 polyps, 444 with colorectal cancer (CRC), and 140 referred for APC mutation analysis in which a germline mutation was not identified. Methods: Genotyping for Y165C and G382D was performed by Pyrosequencing. Results: Biallelic mutations for Y165C and/or G382D were not found in any of those undergoing screening colonoscopy with 0–3 polyps (n = 400), in those APC-negative patients with MYH mutations were not found among patients whose tumors showed the presence of defective DNA mismatch repair (n = 62). However, the presence of biallelic germline MYH mutations correlated with the presence of ≥20 adenomatous polyps. Interestingly, 2 of the 116 individuals with CRC diagnosed at 50 years of age or younger also presented with biallelic germline mutations in MYH . Conclusions: These data suggest that screening of MYH should be considered not only in patients with multiple polyps but also in patients with early-onset CRC.