Association between genetic polymorphisms related to DNA repair or xenobiotic pathways and gastric premalignant conditions

Anticancer Res. 2011 Apr;31(4):1459-65.


Background: Genetic factors related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to Helicobacter pylori (H. pylori)-related gastric carcinogenesis. The association between XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms with gastric intestinal metaplasia, severity of histological gastritis, and peptic ulcer diseases were evaluated in a Japanese population.

Patients and methods: XRCC1 Arg399Gln and Arg194Trp, GSTP1 Ile104Val and GSTT1, GSTM1 null polymorphisms were genotyped in 280 cancer-free individuals, including 52 gastric and 31 duodenal ulcer patients.

Results: Among the five polymorphisms, a significant association between the GSTT1 and GSTM1 null genotypes and increased risk of intestinal metaplasia was found (GSTT1 null: OR=2.42, 95% CI=1.28-4.60, p=0.007, GSTM1 null: OR=2.18, 95% CI=1.15-4.13, p=0.019). When the severity of gastric atrophy was classified into the following three groups: non-atrophy (NA) (atrophy score=0 and metaplasia score=0); severe atrophy (SA) (atrophy score≥2 or metaplasia score≥2) and mild atrophy (MA) (all others), both the GSTT1 and GSTM1 null genotypes held significantly higher risk for developing more severe gastric atrophy (GSTT1 null, SA vs. others: OR=1.95, 95% CI=1.07-3.52, p=0.028, GSTM1 null, NA vs. others: OR=2.57, 95% CI=1.16-5.67, p=0.019, SA vs. others: OR=1.90, 95% CI=1.06-3.42, p=0.032). A significant association was also found between GSTM1 null genotype and increased risk of ulcer diseases (all ulcers: OR=2.42, 95% CI=1.37-4.26, p=0.002, gastric ulcer: OR=2.18, 95% CI=1.11-4.29, p=0.025, duodenal ulcer: OR=2.62, 95% CI=1.15-6.00, p=0.023).

Conclusion: Both the GSTT1 and GSTM1 null genotypes are associated with gastric pre-malignant conditions.

Publication types

  • Comparative Study

MeSH terms

  • Asian People
  • Biomarkers, Tumor / genetics
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Duodenal Ulcer / genetics
  • Duodenal Ulcer / microbiology
  • Duodenal Ulcer / pathology
  • Female
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Glutathione Transferase / genetics*
  • Helicobacter Infections / genetics
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / genetics
  • Humans
  • Male
  • Metaplasia / genetics
  • Metaplasia / microbiology
  • Metaplasia / pathology
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / microbiology
  • Precancerous Conditions / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology
  • Stomach Ulcer / genetics
  • Stomach Ulcer / microbiology
  • Stomach Ulcer / pathology
  • X-ray Repair Cross Complementing Protein 1
  • Xenobiotics


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Xenobiotics
  • glutathione S-transferase T1
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1