Toll-Like Receptor 4+3725 G/C Polymorphism, Helicobacter pylori Seropositivity, and the Risk of Gastric Atrophy and Gastric Cancer in Japanese
Toll-Like Receptor 4+3725 G/C Polymorphism, Helicobacter pylori Seropositivity, and the Risk of Gastric Atrophy and Gastric Cancer in Japanese
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DOI：
10.1111/j.1523-5378.2009.00659.x
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发表时间：
2009-02-01
期刊：
影响因子：
4.4
通讯作者：
Hamajima, Nobuyuki
中科院分区：
文献类型：
--
作者：
Hishida, Asahi;Matsuo, Keitaro;Hamajima, Nobuyuki
Toll样受体4（TLR 4）Asp 299 Gly和Thr 399 Ile多态性是高加索人和印度人胃癌或其前体癌的危险因素，但这些多态性在日本人中不存在。本研究以2001年至2005年在爱知县癌症中心医院就诊的583名经组织学确诊的胃癌患者和1592名年龄和性别匹配的对照门诊患者为研究对象，调查了TLR 4的另一种功能性多态性--TLR 4 + 3725 G/C多态性与日本人胃癌和胃萎缩风险的关系。血清抗H.检测幽门螺杆菌IgG抗体和胃蛋白酶原，以评价H. pylori感染和胃萎缩。用logistic模型计算OR值和95%可信区间，在血清学阳性的受试者中，年龄和性别校正的胃萎缩OR值为1.17（95%CI：0.91-1.50），C/C为1.20（95%CI：0.76-1.89），G/C+C/C为1.18（95%CI：0.93-1.49）。H. pylori血清学阳性受试者中G/C为1.43（95%CI：0.99-2.06），C/C为1.47（95%CI：0.76-2.88），G/C+C/C为1.43（95%CI：1.01-2.04）。本研究发现TLR 4 + 3725 G/C多态性是H.幽门螺杆菌血清阳性日本人。我们的研究结果强调了在具有相同背景的东亚人群中，由于TLR 4多态性导致的宿主先天免疫变化作为胃癌前病变的遗传易感性的重要性。
Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms were reported to be a risk factor of gastric carcinoma or its precursors in Caucasian and Indian population, but these polymorphisms are absent in Japanese. We investigated the associations of TLR4 +3725 G/C polymorphism, another functional polymorphism of TLR4, with risk of gastric cancer and gastric atrophy in Japanese.Study subjects were 583 histologically diagnosed gastric cancer patients and age- and sex-matched 1592 control outpatients, who visited Aichi Cancer Center Hospital from 2001 to 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 the seropositive subjects, the age- and sex-adjusted OR of gastric atrophy was 1.17 (95%CI: 0.91-1.50) for G/C, 1.20 (95%CI: 0.76-1.89) for C/C, and 1.18 (95%CI: 0.93-1.49) for G/C+C/C relative to G/G genotype. The age- and sex-adjusted OR of severe gastric atrophy among H. pylori seropositive subjects was 1.43 (95%CI: 0.99-2.06) for G/C, 1.47 (95%CI: 0.76-2.88) for C/C, and 1.43 (95%CI: 1.01-2.04) for G/C+C/C. The OR of gastric cancer compared with gastric atrophy controls was not statistically significant.Our study found that TLR4 +3725 G/C polymorphism was a risk factor of severe gastric atrophy in H. pylori seropositive Japanese. Our results underscored the significance of the variations in host innate immunity due to TLR4 polymorphism as genetic predispositions to gastric precancerous lesions in Eastern Asian populations with the same backgrounds.