Genetic investigation of DNA-repair pathway genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1 in sporadic colon cancer

Int J Cancer. 2007 Aug 1;121(3):555-8. doi: 10.1002/ijc.22735.


Mutations in DNA repair genes have previously been identified as causative factors for hereditary nonpolyposis colon cancer (HNPCC). Recent evidence also supports an association between DNA sequence variation in these genes and sporadic colorectal carcinoma (CRC). Genetic investigation of DNA repair genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1, as possible susceptibility factors for sporadic CRC, was done using both a haplotype tagging and a candidate (i.e. coding) single nucleotide polymorphism (SNP) approach. Some 1,068 patients with operated CRC (median age at diagnosis: 59 years) were compared to 738 sex-matched control individuals (median age: 67 years). Haplotype tagging SNPs, previously reported risk variants and all known coding SNPs with a minor allele frequency >0.005 were genotyped in PMS2 (N = 10), MLH1 (N = 11), MSH2 (N = 18), MSH6 (N = 15), MUTYH (N = 7), OGG1 (N = 11) and MTH1 (N = 3). No evidence for an association between CRC and any of the 7 genes was detected, neither with the tagging or coding SNPs nor in a sliding window haplotype analysis (all nominal p-values >0.05). The previously reported risk variants D132H in MLH1 and R154H in OGG1 were not even observed in the German population. Genetic CRC risk factors so far identified in DNA repair genes seem to be rare and population-specific. Their association with the disease could not be replicated in German CRC samples. It remains to be elucidated by more systematic, large-scale experiments whether common variants in the same genes, but present across populations, represent risk factors for sporadic CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adenosine Triphosphatases / genetics
  • Aged
  • Case-Control Studies
  • Colonic Neoplasms / genetics*
  • DNA Glycosylases / genetics
  • DNA Repair Enzymes / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation
  • Nuclear Proteins / genetics
  • Phosphoric Monoester Hydrolases / genetics
  • Polymorphism, Single Nucleotide


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • Nuclear Proteins
  • Phosphoric Monoester Hydrolases
  • DNA Glycosylases
  • mutY adenine glycosylase
  • oxoguanine glycosylase 1, human
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • 8-oxodGTPase
  • DNA Repair Enzymes