IL-1β和IL-1受体拮抗剂基因多态性与胃癌遗传易感性的相关性研究

Relationships Among Interleukin-1β,Interleukin-1 Receptor Antagonist Gene Polymorphism and Susceptibility to Gastric Cancer

目的研究白细胞介素1β基因(IL-1β)及白细胞介素-1受体拮抗剂基因(IL-1RN)的基因多态性在胃癌患者及正常人群中的分布,分析其各基因型与胃癌易感性的相关性。方法采用病例对照研究方法,收集140例胃癌患者和165名性别、年龄频数匹配的正常健康人外周血或癌旁组织标本,提取DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测,比较各位点基因型。结果 IL-1β基因-31、-511和+3954位点各基因型在胃癌组和对照组中的分布均无显著性差异(P>0.05)。IL-1RN基因发现2R/2R、2R/4R、3R/4R和4R/4R四种基因型,其频率在胃癌患者中分别是0.7%、15.7%、2.9%和80.7%,而在对照组中分别是0、5.5%、0和94.5%,携带2R/4R基因型者发生胃癌的危险是4R/4R基因型的3.37倍,但差异未显示出统计学意义(P=0.557,χ2=2.076)。携带IL-1RN2R等位基因在胃癌患者中的出现频率是8.6%,高于正常人的频率2.7%,表明携带IL-1RN2R等位基因者患胃癌的风险增加3.4倍,但统计分析显示差异未达到统计学意义(P=0.781,χ2=0.494)。结论尚无直接证据证明IL-1β和IL-1RN各基因多态性与胃癌易感性有关,但携带IL-1RN2R等位基因可能提高胃癌患病风险,其潜在作用尚需大样本研究的进一步探讨。

Objectives To investigate the genetic polymorphisms of interleukin-1β （IL-1β） and interleukin-1 receptor antagonist gene （IL-1RN） in gastric cancer, and to explore the relationships of these genetic polymorphisms to the susceptibility of gastric cancer. Methods The polymorphisms of IL-1β and IL-1RN genes were analyzed by PCR-restriction fragment length polymorphism （PCR-RFLP） after extracting the genomic DNA from 140 gastric cancer patients and 165 age- and sex-matched healthy controls. Results The polyrnorphisms of IL-1β promoter region-31, -511 and ＋ 3954 locus have no significant difference between gastric cancer patients and healthy subjects. Four kinds of polymorphisms of IL-1RN were found as 2R/2R, 2R/4R, 3R/4R and 4R/4R, and the frequency in gastric cancer patients were 0. 7%, 15.7%, 2.9% and 80.7%, respectively, while the frequency in healthy controls were 0, 5.5%, 0 and 94.5%, respectively. Compared to 4R/4R genotype, a 3.37 fold increased risk of gastric cancer were found in 2R/4R genotype, but the difference was not significant （P = 0. 557, χ^2 =- 2. 076）. IL-1RN 2R allele frequencies in gastric cancer and healthy controls were 8. 6% and 2. 7%, respectively, which showed the risk to be gastric cancer increased 3.4 times, but the difference was not significant （P=0. 781, χ^2 =0.494）. Conclusion There is no evidence to support that the polymorphism of IL-1β and IL-1RN gene had relationship with gastric cancer. However, the risk of developing gastric cancer might be raised when the IL-1RN 2R allele exist.