Goto Yasuyuki, Ando Takafumi, Nishio Kazuko, Kawai Sayo, Ishida Yoshiko, Naito Mariko, Goto Hidemi, Hamajima Nobuyuki
Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Int J Med Sci. 2006 Nov 1;4(1):1-6. doi: 10.7150/ijms.4.1.
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.
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.
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.
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.
多种单核苷酸多态性（SNP）已解释了幽门螺杆菌（H. pylori）与胃萎缩及癌症之间的关联。本研究调查了Grb2相关结合蛋白1（Gab1）多态性以及编码含src同源2结构域蛋白酪氨酸磷酸酶-2（SHP2）的PTPN11基因与Gab1基因的组合在幽门螺杆菌血清阳性受试者中与胃癌和胃萎缩的关联。
对454名年龄在35至85岁、无胃癌病史的日本健康体检者（126名男性和328名女性）以及202名年龄在33至94岁、经病理确诊为胃腺癌的胃癌患者（134名男性和68名女性）检测了Gab1内含子2处的单核苷酸多态性（JST164345）。
Gab1 A/A型对幽门螺杆菌血清阳性的OR值降低为0.25（95%置信区间（CI）：0.08 - 0.71）。在血清阳性的健康对照者中，Gab1 G/A + A/A型对胃萎缩的OR值具有显著性（OR = 1.95，95% CI：1.12 - 3.40）。与PTPN11 G/A + A/A和Gab1 G/G（风险最低的组合）作为对照相比，PTPN11 G/G和Gab1 G/A + A/A的血清阳性个体胃萎缩风险最高且具有显著性（OR = 3.49，95% CI：1.54 - 7.90）。然而，未观察到PTPN11与Gab1之间的基因 - 基因相互作用（OR = 1.39，95% CI：0.41 - 4.66）。与胃癌病例相比，Gab1不影响萎缩/化生 - 胃癌序列步骤。
本研究表明，Gab1多态性与血清阳性健康对照者中幽门螺杆菌感染低风险及胃萎缩高风险相关，且PTPN11 G/G和Gab1 G/A + G/G的血清阳性个体胃萎缩风险最高。这些发现需要在更大规模的研究中得到证实。
