白细胞介素1B及RN基因多态性与胃癌易感性的关系

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

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 5 0例胃癌癌旁正常组织和 5 0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AluI限制性内切酶对PCR产物进行消化 ,然后经琼脂糖凝胶电泳分别对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 5 3% ,- 31T等位基因频率则分别为 2 5 %和 4 7%。正常人和胃癌患者中 3种基因型频率分别为 - 31C / - 31C :5 6 % (2 8/ 5 0 )和 30 % (15 / 5 0 ) ;- 31C / - 31T :38% (19/ 5 0 )和 4 6 % (2 3/ 5 0 ) ;- 31T / -31T :6 % (3/ 5 0 )和 2 4 % (12 / 5 0 )。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 .0～2 7 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 4 9% ,IL 1RN 2等位基因频率则分别为2 7%和 5 1%。正常人和胃癌患?

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 relatioship 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% agrose 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 reespectively. 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 0～27 6) and of 2 3 for-31C/-31T (95% CI, 0 9～5 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 trespectively. The frequency of 1/2 was 38% (19/50) and 50% (25/50) in normal controls and patients trespectively. The frequency of 2/2 was 8% (4/50) and 26% (13/50) in normal controls and patients trespectively. 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 13～25 09) and of 2 96for 1/2 heterozygotes (95% CI 1 22～7 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.