title: Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.
abstract: BACKGROUND
  Previous studies have revealed the significance of Helicobacter pylori (H. pylori) infection as a risk factor of gastric cancer. Cytotoxin-associated gene A (cagA) positivity has been demonstrated to determine the clinical outcome of H. pylori infection in the presence of SHP-2 (src homology 2 domain-containing protein tyrosine phosphatase-2). This study aimed to examine the formerly reported association of G/A PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) polymorphism (rs2301756) with gastric atrophy, as well as the association with gastric cancer in a Japanese population using a large sample size.
  
  
  METHODS
  Study subjects were 583 histologically diagnosed patients with gastric cancer (429 males and 154 females) and age- and sex-frequency-matched 1,636 non-cancer outpatients (1,203 males and 433 females), who visited Aichi Cancer Center Hospital between 2001-2005. Serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model.
  
  
  RESULTS
  Among H. pylori seropositive non-cancer outpatients, the age- and sex-adjusted OR of gastric atrophy was 0.82 (95% CI 0.62-1.10, P = 0.194) for G/A, 0.84 (95% CI 0.39-1.81, P = 0.650) for A/A, and 0.83 (95% CI 0.62-1.09, P = 0.182) for G/A+A/A, relative to G/G genotype, and that of severe gastric atrophy was 0.70 (95% CI 0.47-1.04, P = 0.079), 0.56 (95% CI 0.17-1.91, P = 0.356), and 0.68 (95% CI 0.46-1.01, P = 0.057), respectively. Among H. pylori infected subjects (H. pylori seropositive subjects and seronegative subjects with gastric atrophy), the adjusted OR of severe gastric atrophy was further reduced; 0.62 (95% CI 0.42-0.90, P = 0.012) for G/A+A/A. The distribution of the genotype in patients with gastric cancer was not significantly different from that for H. pylori infected subjects without gastric atrophy.
  
  
  CONCLUSIONS
  Our study results revealed that those with the A/A genotype of PTPN11 rs2301756 polymorphism are at lower risk of severe gastric atrophy, but are not associated with a decreased risk of gastric cancer, which partially supported our previous finding that the polymorphism in the PTPN11 gene encoding SHP-2 was associated with the gastric atrophy risk in H. pylori infected Japanese. The biological roles of this PTPN11 polymorphism require further investigation.
authors: Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Japan. a-hishi@med.nagoya-u.ac.jp
authors: Asahi
authors: A
authors: Hishida
authors: Keitaro
authors: K
authors: Matsuo
authors: Yasuyuki
authors: Y
authors: Goto
authors: Mariko
authors: M
authors: Naito
authors: Kenji
authors: K
authors: Wakai
authors: Kazuo
authors: K
authors: Tajima
authors: Nobuyuki
authors: N
authors: Hamajima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D001284:Atrophy / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D016481:Helicobacter Infections / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010435:Pepsinogens / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013270:Stomach / Q000382:microbiology* / Q000473:pathology*; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*
chemical_list: D000907:Antibodies, Bacterial; D010435:Pepsinogens; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11