Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy.
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.
Goto
Yasuyuki
Y
Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. y-goto@med.nagoya-u.ac.jp
Ando
Takafumi
T
Nishio
Kazuko
K
Kawai
Sayo
S
Ishida
Yoshiko
Y
Naito
Mariko
M
Goto
Hidemi
H
Hamajima
Nobuyuki
N
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D016481:Helicobacter Infections / Q000209:etiology* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013274:Stomach Neoplasms / Q000209:etiology; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases