Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.
Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.
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DOI：
10.1186/1471-230x-9-51
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发表时间：
2009-07-09
影响因子：
2.4
通讯作者：
Hamajima N
中科院分区：
文献类型：
--
作者：
Hishida A;Matsuo K;Goto Y;Naito M;Wakai K;Tajima K;Hamajima N
以往的研究表明，幽门螺杆菌(H.Pylori)感染是胃癌的危险因素。细胞毒素相关基因A(CagA)阳性已被证明在SHP-2(src同源2结构域蛋白酪氨酸磷酸酶-2)存在的情况下决定Hp感染的临床结局。本研究旨在利用大样本量研究先前报道的G/A PTPN11(蛋白酪氨酸磷酸酶，非受体类型11)多态(Rs2301756)与胃萎缩的关系，以及与日本人群中胃癌的关系。研究对象为2001年至2005年在爱知肿瘤中心医院就诊的583名组织学确诊的胃癌患者(429名男性和154名女性)和1636名年龄和性别频率匹配的非癌症门诊患者(1203名男性和433名女性)。血清抗H。分别检测幽门螺杆菌抗体和胃蛋白酶原以判断幽门螺杆菌感染和胃萎缩情况。用Logistic模型计算优势比(OR)和95%可信区间(CI)。在Hp阳性的非癌症门诊患者中，胃萎缩的年龄和性别调整OR值分别为G/A 0.82(95%CI 0.62~1.10，P=0.194)、A/A 0.84(95%CI 0.39~1.81，P=0.650)和G/A+A/A 0.83(95%CI 0.62~1.09，P=0.182)，重度胃萎缩的OR值为0.70(95%CI 0.47~1.04)。P=0.079)、0.56(95%可信区间0.17~1.91，P=0.356)和0.68(95%可信区间0.46~1.01，P=0.057)。在幽门螺杆菌感染者(幽门螺杆菌阳性者和血清阴性者伴胃萎缩者)中，重度胃萎缩的调整OR进一步降低，G/A+A/A的调整OR为0.62(95%CI0.42~0.90，P=0.012)。我们的研究结果显示，携带PTPN11 rs2301756基因A/A多态的人患严重胃萎缩的风险较低，但与患胃癌的风险不相关，这部分支持了我们先前的发现，即编码SHP-2的PTPN11基因的多态与幽门螺杆菌感染的日本人的胃萎缩风险有关。这种PTPN11基因多态的生物学作用有待进一步研究。
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. 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. 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. 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.