细胞因子基因多态性与胃腺癌发生及其临床病理特点的关系

Relationship between cytokine gene polymorphisms on development and clinical characteristics of gastric adenocarcinoma

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)与胃腺癌合并或未合并幽门螺杆菌(Hp)感染的关系。方法采用基因芯片技术检测130例胃腺癌患者(胃癌组)和142例健康对照人群(对照组)中TNF-α-238G/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)测定两组血清中Hp-IgG/IgM/IgA型抗体浓度。结果胃癌组Hp的感染阳性率明显高于对照组(P<0.01,相对危险度[OR]=2.59)。TNF-α-238GA基因型和A等位基因频率,胃癌组明显高于对照组(P<0.01,OR=2.44;P<0.01,OR=2.13);Hp阳性胃癌组明显高于Hp阴性胃癌(P<0.05,OR=4.53;P<0.01,OR=3.52);低分化胃癌组显著高于高分化胃癌组(P<0.05,OR=4.16)。胃癌组IL-6-572CC基因型频率明显低于对照组(P<0.01,OR=0.17)。未见TNF-α和IL-6其他位点的SNP与胃癌组或Hp阳性胃癌组有任何相关性。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 relationships between single nucleotide polymorphisms （ SNPs ） of tumor necrosis factor-α （ TNFα ） or interleukin-6 （ IL-6 ） promoter genes and gastric adenocarcinoma with or with out helicobacter pylori（HP） infection. Methods The SNPs of TNF-α （-238G/A and -308G/A ） and IL-6（-597G/A,-174G/C and -572G/C） were determined by gene chip in 130 patients with gastric adenocarcinoma and 142 healthy controls. The sera concentrations of lgG, IgM and IgA of HP antibodies were measured by ELISA in all cases and controls. Results Pylori infection was detected in 69. 2% of 130 patients and 46. 5% of 142 controls（ P 〈 0. 01 , odds ratio[ OR] = 2. 59,95% confidence interval [95%CI] = 1.58 -3. 93）. Frequencies of TNF-α-238GA genotype and A allele in patients with gastric adenocarcinoma were significantly higher than those in healthy controls （ P 〈 0.01 , OR = 2.44 , 95 % CI = 1.41 - 4. 22 and P 〈 0. 01 , OR = 2. 13, 95% CI = 1. 22 - 3. 73, respectively）. Frequencies of TNF-α-238GA genotype and A allele in patients with gastric adenocarcinoma with HP infection were significantly 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, 01 , OR = 3. 52,95% CI = 1 , 64-7. 54 , respectively ） , Frequencies of TNF-α-238 GA genotype and A allele in patients with poorly-differentiated gastric adenocarcinoma were significantly higher＇ than those in well-differentiated group （ P 〈 0. 05, OR = 4. 16,95% CI = 1. 21 - 14. 32）, The proportion of individuals carrying the IL-6-572CC genotype was significantly lower in the patients with gastric adenocarcinoma than in the controls（ P 〈0.01 ,OR =0. 17,95% CI =0, 064 -0.465）, No association was found between any of the other polymorphisms and patients with gastric adenocarcinoma or patients with gastric adenocarcinoma and HP infection. Conclusions TNF-α-238 GA genotype and A allele were significantly related to patients with gastric adenocarcinoma or patients with gastric adenocarcinoma and HP infection. IL-6-572 CC genotype can have a protective function against susceptibility to gastric cancer.