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.: Home > International Journal of Medical Sciences > 2007 > Volume 4 Number 1 > Yasuyuki Goto 1, Takafumi Ando 2, Kazuko Nishio 1, Sayo Kawai 1, Yoshiko Ishida 1, Mariko Naito 1, Hidemi Goto 2, Nobuyuki Hamajima 1

Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy

Yasuyuki Goto 1, Takafumi Ando 2, Kazuko Nishio 1, Sayo Kawai 1, Yoshiko Ishida 1, Mariko Naito 1, Hidemi Goto 2, Nobuyuki Hamajima 1
1. Department of Preventive Medicine / Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan 2. Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Abstract :

Background: Various single nucleotide polymorphisms (SNPs) have explained the association between
Helicobacter pylori (H. pylori) and gastric atrophy and cancer. This study investigated the associations of Grb2 associated binder 1 (Gab1) polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2) and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects. Methods: A single nucleotide polymorphism at intron 2 of Gab1 (JST164345) was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 without a history of gastric cancer and 202
gastric cancer patients (134 males and 68 females) aged 33 to 94 with pathologically confirmed diagnosis of gastric adenocarcinoma. Results: The decreased OR of the Gab1 A/A for H. pylori seropositivity was 0.25 (95% confidence interval (CI): 0.08-0.71). Among seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was significant (OR=1.95, 95% CI: 1.12 -3.40). Seropositive individuals with PTPN11 G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with significance (OR=3.49, 95% CI: 1.54-7.90) relative to PTPN11 G/A+A/A and Gab1 G/G, the lowest risk combination, as a reference. However, the gene-gene interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41-4.66). Compared to gastric cancer case, the Gab1 did not influence the step of atrophy/metaplasia-gastric cancer sequence. Conclusions: This study represents that the Gab1 polymorphism was associated with the low risk of H. pylori infection and the high risk of gastric atrophy among seropositive healthy controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were associated with the greatest risk of gastric atrophy. These  findings require confirmation in much larger studies.

Keywords :
Gab1, SHP-2, Polymorphism, Gastric atrophy, Helicobacter pylori infection

Date Deposited : 28 Jul 2011 12:53

Last Modified : 28 Jul 2011 12:53

Official URL: http://www.medsci.org/archive

Volume 4, Number 1, - 2007 , ISSN 1449-1907

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