title: Association between genetic polymorphisms related to DNA repair or xenobiotic pathways and gastric premalignant conditions.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  Both the GSTT1 and GSTM1 null genotypes are associated with gastric pre-malignant conditions.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan. tomomiccyu@yahoo.co.jp
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Joh
authors.initials: J
authors.lastname: Yonemura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masami
authors.initials: M
authors.lastname: Iwata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
mesh_terms: D044466:Asian People; D014408:Biomarkers, Tumor / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004381:Duodenal Ulcer / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D016481:Helicobacter Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D013276:Stomach Ulcer / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1; D015262:Xenobiotics
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D000076105:X-ray Repair Cross Complementing Protein 1; D015262:Xenobiotics; C000619371:XRCC1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human