TNF-α及IL-6基因多态性与胃腺癌易感性的关系

Relationship between tumor necrosis factor-α and interleukin-6 gene polymorphism and susceptibility to gastric cancer

目的:探讨肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)基因单核苷酸多态性(SNP)与胃腺癌及幽门螺杆菌(HP)感染胃腺癌发生发展的相关性。方法:采用基因芯片技术检测65例胃腺癌患者和71例健康对照人群中TNF--α238G/A-、308G/A和IL-6-597G/A、-174G/C、-572G/C位点多态性。同时应用酶联免疫吸附试验(ELISA)测定其血清中HP-IgG/IgM/IgA型抗体浓度。结果:感染HP胃腺癌患者的阳性率明显高于感染HP的对照组(P=0.007,相对危险度[OR]=2.53,95%可信区间[95%CI]=1.28-5.24)。胃腺癌组TNF--α238GA基因型和A等位基因频率明显高于对照组(P=0.024,OR=2.44,95%CI=1.11-5.37;P=0.039,OR=2.13,95%CI=1.03-4.41),在HP阳性胃腺癌组明显高于HP阴性胃腺癌(P<0.05,OR=4.53,95%CI=1.16-17.68;P<0.05,OR=3.52,95%CI=0.98-12.64)。胃腺癌组IL-6-572CC基因型频率明显低于对照组(P=0.014,OR=0.17,95%CI=0.04-0.81)。未见TNF-α和IL-6其他位点的SNP与胃腺癌组或HP阳性胃腺癌组有任何相关性。结论:TNF-238GA基因型及其等位基因A与胃腺癌或感染HP的胃腺癌易感性相关,而IL-6-572CC基因型则能降低胃腺癌易感性。

Objective：To investigate the relation between the single nucleotide polymorphisms（SNPs） of tumor necrosis factor-α（TNF-α） or interleukin-6（IL-6） promoter genes and susceptibility to the patients with gastric adenocarcinoma or the patients with gastric adenocareinoma with helicobacter pylori（HP） infection. Methods：The SNPs of the TNF-α（-238G/A and -308G/A） and IL-6（-597G/A,-174G/C and -572G/C） were determined by gene chip in 65 patients with gastric adenocarcinoma and 71 healthy controls. The sera concentrations of IgG, IgM and IgA of HP antibodies were measured by ELISA. Results：H. pylori infection was detected in 69.2% of 65 patients and 46.5% of 71 controls （P = 0.007, odds ratio [OR] = 2.53,95% confidence interval [95%CI] = 1.28 - 5.24）. Frequencies of TNF-a-238GA genotype and A allele in patients with gastric adenocarcinoma were significantly higher than those in healthy controls（ P =0.024, OR = 2.44,95% CI = 1.11 - 5.37 and P = 0. 039, OR = 2.13,95% CI = 1.03 - 4.41, respectively）. Frequencies of TNF-a-238GA genotype and A allele in patients with gastric adenocarcinoma with HP infection were significandy higher than those in HP-negtive patients with gastric adenocarcinoma（ P 〈 0.05, OR = 4.53, 95% CI = 1.16 - 17.68 and P 〈 0.05,OR = 3.52, 95%CI = 0.98-12.64,respectively）. The proportion of individuals carrying the IL-6- 572CC genotype was significantly lower in patients with gastric adenocarcinoma than in the controls（ P = 0.014, OR = 0.17, 95 % CI = 0.04 - 0.81 ）. No association was found between any of the other polymorphisms and patients with gastile adenocarcinoma or patients with gastric adenocarcinoma with HP infection. Conclusion：There are significant correlation between TNF-a-238GA genotype and A allele and gastric adenocarcinoma or gastric adenocarcinoma with HP infec- tion. IL-6-572CC genotype is a protective function against cancers.