Polymorphisms of DNA repair and xenobiotic genes predispose to CpG island methylation in non-neoplastic gastric mucosa

Helicobacter. 2011 Apr;16(2):99-106. doi: 10.1111/j.1523-5378.2011.00821.x.


Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non-neoplastic gastric mucosa.

Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP-kinase and CDH1) loci, assessed by Methylation-Specific-Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated.

Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR = 0.30, 95%CI = 0.13-0.71, p = .0055) and CIHM high (OR = 0.42, 95%CI = 0.19-0.97, p = .04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p = .02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50 years and older generations (OR = 1.63, 95%CI = 1.01-2.62, p = .045).

Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP-kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM-related gastric carcinogenesis.

MeSH terms

  • Aged
  • Codon / genetics
  • CpG Islands / genetics*
  • DNA Methylation / genetics*
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Stomach Neoplasms / genetics
  • X-ray Repair Cross Complementing Protein 1


  • Codon
  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human