白细胞介素1B及RN基因多态性与胃癌易感性的关系

目的 探讨白细胞介素1B(IL-1B)基因启动子区域－31C／T和白细胞介素－1受体拮抗剂（IL－1RN）基因在国人胃癌及正常人群中的多态性,初步分析其基因型与胃癌的相关性。方法 收集50例胃癌癌旁正常组织和50名正常健康人外周血标本,提取DNA并分别对1B、RN基因进行PCR扩增,其中IL－1B基因用Alu I限制性内切酶对PCR产物进行消化,然后经琼脂糖胶电泳分别对IL－1B、RN基因多态性进行分析。结果 IL－1B基因－31C等位基因频率在正常人和胃癌患者中分别为75％和53％,－31T等位基因频率则分别为25％和47％。正常人和胃癌患者中3种基因型频率分别为－31C／－31C：56％（28／50）和30％（15／50）;－31C／－31T：38％（19／50）和46％（23／50）;－31T／－31T：6％（3／50）和24％（12／50）。携带－31T等位基因增加罹患胃癌的危险性,－31C／－31T杂合子和－31T／－31T纯合子分别增加2.3（OR＝2。3,95％,CI＝0.9－5.4）和7.5倍（OR＝7.5,95%,CI=2.0-27.6)。IL－1RN基因的5种不同组合等位基因,本研究中只发现1／1、1／2、2／2三种多态。其中IL－1RN*1等位基因频率在正常人和胃癌患者中分别为73％和49％,IL－1RN*2等位基因频率则分别为27％和51％。正常人和胃癌患者中3种基因型频率分别为1/1:54%(27/50)和24％（12／50）;1/2:38%(19/50)和50％（25／50）;2／2：8％（4／50）和26％（13／50）。携带IL－1RN*2等位基因增加罹患胃癌的危险性,1／2杂合子和2／2纯合子比1／1纯合子分别增加2.96倍（OR＝2.96,95%,CI=1.22-7.21)和7.31倍（OR=7.31,95%CI=2.13-25.09)。结论 IL－1B基因启动子区域－31C／T多态性与国人胃癌易感性相关;IL－1RN基因1／2、2／2多态性与国人胃癌易感性相关,二者可能作为胃癌遗传易感性的检测指标,用于胃癌易患个体的预警和胃癌的预防。

Relationship between interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms and susceptibility to gastric cancer

OBJECTIVE: To investigate the polymorphisms of interleukin-1B (IL-1B) promotor region 31 C/T and interleukin-1 receptor antagonist (IL-1RN) gene and the relationship between the genotype of IL-1 and IL-1RN and susceptibility to gastric cancer in Chinese population. METHODS: Genomic DNA was extracted from the juxta-cancerous normal mucosal biopsies of 50 patients with gastric cancer taken by endoscopy and from the peripheral lymphocytes of 50 normal controls and then was subjected to PCR amplification. The PCR product was digested by restriction endonuclease Alu I. The product of digestion was subjected to 2% agarose gel electrophoresis and ethidium bromide staining. RESULTS: The IL-1B -31C allele was detected in 75% of normal controls and 53% of patients, while the IL-1B -31T allele was detected in 25% of normal controls and 47% of patients. The frequency of -31C/-31C was 56% (28/56) and 30% (15/50) in normal controls and patients respectively. The frequency of -31C/-31T was 38% (19/56) and 46% (23/50) in normal controls and patients respectively. The frequency of -31T/-31T was 6% (3/56) and 24% (12/50) in normal controls and patients respectively. IL-1B -31T carriers were at increased risk of gastric cancer with an odds ratio of 7.5 for -31T/-31T homozygotes (95% CI, 2.0 approximately 27.6) and of 2.3 for -31C/-31T (95% CI, 0.9 approximately 5.4) respectively. Only three of the five kinds of polymorphism of IL-1RN (1/1, 1/2 and 2/2) were found in this study. The frequency of 1/1 was 54% (27/50) and 24% (12/50) in normal controls and patients respectively. The frequency of 1/2 was 38% (19/50) and 50% (25/50) in normal controls and patients respectively. The frequency of 2/2 was 8% (4/50) and 26% (13/50) in normal controls and patients respectively. The IL-1RN * 1 allele was detected in 73% of normal controls and 49% of patients; while the IL-1RN * 2 allele was detected in 27% of normal controls and 51% of patients. IL-RN * 2 carriers were at increased risk of gastric cancer with an odds ratio of 7.31 for 2/2 homozygotes (95% CI 2.13 approximately 25.09) and of 2.96for 1/2 heterozygotes (95% CI 1.22 approximately 7.21), respectively. CONCLUSION: The polymorphism of promotor region -31C/T of IL-1B gene and the polymorphism of IL-1RN genes 1/2 and 2/2 are associated with the susceptibility of gastric cancer in Chinese. Carrying -31T allele increases the risk of gastric cancer. Polymorphism of IL-1RN and IL-1B gene may be used as indicators of susceptibility of gastric carcinogenesis.