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

<p>Abstract</p> <p>Background</p> <p>Previous studies have revealed the significance of <it>Helicobacter pylori </it>(<it>H. pylori</it>) infection as a risk factor of gastric cancer. Cytotoxin-associated gene A (<it>cagA</it>) positivity has been demonstrated to determine the clinical outcome of <it>H. pylori </it>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 <it>PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) </it>polymorphism (rs2301756) with gastric atrophy, as well as the association with gastric cancer in a Japanese population using a large sample size.</p> <p>Methods</p> <p>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-<it>H. pylori </it>IgG antibody and pepsinogens were measured to evaluate <it>H. pylori </it>infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model.</p> <p>Results</p> <p>Among <it>H. pylori </it>seropositive non-cancer outpatients, the age- and sex-adjusted OR of gastric atrophy was 0.82 (95% CI 0.62–1.10, <it>P </it>= 0.194) for <it>G/A</it>, 0.84 (95% CI 0.39–1.81, <it>P </it>= 0.650) for <it>A/A</it>, and 0.83 (95% CI 0.62–1.09, <it>P </it>= 0.182) for <it>G/A</it>+<it>A/A</it>, relative to <it>G/G </it>genotype, and that of severe gastric atrophy was 0.70 (95% CI 0.47–1.04, <it>P </it>= 0.079), 0.56 (95% CI 0.17–1.91, <it>P </it>= 0.356), and 0.68 (95% CI 0.46–1.01, <it>P </it>= 0.057), respectively. Among <it>H. pylori </it>infected subjects (<it>H. pylori </it>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, <it>P </it>= 0.012) for <it>G/A</it>+<it>A/A</it>. The distribution of the genotype in patients with gastric cancer was not significantly different from that for <it>H. pylori </it>infected subjects without gastric atrophy.</p> <p>Conclusion</p> <p>Our study results revealed that those with the <it>A/A </it>genotype of <it>PTPN11 </it>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 <it>PTPN11 </it>gene encoding SHP-2 was associated with the gastric atrophy risk in <it>H. pylori </it>infected Japanese. The biological roles of this <it>PTPN11 </it>polymorphism require further investigation.</p

Irregular AC losses with long time constants in large cable-in-conduit conductors

科研費報告書収録論文(課題番号:15360491/研究代表者:濱島高太郎/大型超伝導コイルに発生する不規則な交流損失の原因究明)44