Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer

Int J Cancer. 2004 Apr 20;109(4):554-8. doi: 10.1002/ijc.20020.


Mutations in the base excision repair gene MYH have recently been shown to confer recessive susceptibility to colorectal adenomas and carcinomas. To evaluate the contribution of germline MYH mutations to early-onset colorectal cancer, we screened a series of 358 unselected early-onset cases for germline changes in the coding sequence of the gene. Two cases harbored biallelic germline mutations (0.6%; 95% CI = 0.06-2.0) and 8 single MYH mutations (2.2%; 95% CI = 0.9-4.4). Both cases harboring biallelic MYH mutations had multiple polyps but not profuse polyposis. All cases had distally sited tumors. No biallelic mutations were detected among 354 controls. These results confirm that biallelic MYH mutations confer susceptibility to colorectal cancer but are unlikely to account for more than 3% of early-onset colorectal cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Age of Onset
  • Allelic Imbalance
  • Case-Control Studies
  • Colon / metabolism
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Glycosylases / genetics*
  • Female
  • Genetic Variation*
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Rectum / metabolism
  • United Kingdom


  • DNA Glycosylases
  • mutY adenine glycosylase