title: Polymorphisms of DNA repair and xenobiotic genes predispose to CpG island methylation in non-neoplastic gastric mucosa.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
authors: Tomomitsu
authors: T
authors: Tahara
authors: Tomoyuki
authors: T
authors: Shibata
authors: Masakatsu
authors: M
authors: Nakamura
authors: Masaaki
authors: M
authors: Okubo
authors: Hiromi
authors: H
authors: Yamashita
authors: Daisuke
authors: D
authors: Yoshioka
authors: Joh
authors: J
authors: Yonemura
authors: Takamitsu
authors: T
authors: Ishizuka
authors: Ichiro
authors: I
authors: Hirata
authors: Tomiyasu
authors: T
authors: Arisawa
mesh_terms: D000368:Aged; D003062:Codon / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human