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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.    Conclusion  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.

Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pyloriseropositivity, gastric atrophy and gastric cancer in Japanese