IL-1B及IL-1RN基因多态性与胃癌遗传易感性的关系

Association between functional genetic polymorphisms of IL-1B and IL-1RN and susceptibility to gastric cancers

目的探讨炎症因子IL-1B(T-31C和C-511T)及其拮抗基因IL-1RN基因多态性与胃癌遗传易感性的关系。方法采用病例对照研究,对经组织学确诊的胃腺癌病例180例及其年龄和性别频数匹配的对照308例,以限制性片段长度多态性(RFLP-PCR)方法进行多态性检测,比较不同基因型以及环境因素与胃癌发病风险的关系。结果IL-1B启动子区域T-31C和C-511T基因多态性呈高度连锁不平衡(D’=0.862,R2=0.721,P=0.000),未发现IL-1B(T-31C和C-511T)基因多态性与胃癌之间存在显著性关联,显性模型调整比值比(OR)及其95%可信区间(C I)分别为0.95(0.62-1.47)和0.85(0.55-1.31);IL-1RN变异基因型(1/2和2/2)可增加胃癌的患病风险,但未达到统计学差异(调整OR=1.32,95%C I=0.71-2.36);分层结果显示在幽门螺旋杆菌(H.pylori)感染组中,IL-1RN变异基因型(1/2、2/2)显著增加胃癌的患病风险(调整OR=2.03,95%C I=1.02-4.80)。结论IL-1RN基因多态性和H.pylori感染可能在胃癌的发生和发展中具有协同作用。

Objective To study the association between functional genetic polymorphisms of IL-1B （T-31C, C-511T）, IL-1RN and the susceptibility to gastric cancers. Methods A case-control study was conducted in 180 gastric cancer cases and 308 age- and sexmatched cancer-free controls. Genotypes were detected by PCR-restriction fragment length polymorphism （PCR-RFLP） assays, and association between genotypes, environmental factors and risk of gastric cancers were determined. Results IL-1B T-31C was in strong linkage disequilibrium with IL-IB C-511T （ D＇=0. 862, R^2 = 0. 721, P = 0. 000）. Multivariate logistic regression analysis revealed that the variant genotypes of IL-1 B T-31C and C-511T were not significantly associated with risks for gastric cancers （adjusted OR, 0. 95 and 95% CI, 0.62 - 1.47 for IL-1B T-31C; and adjusted OR, 0.85 and 95% CI, 0. 55 - 1.31 for IL-1B C-511T）. The variant genotypes （1/2, 2/2） in IL-1RN were associated with a non-significantly increased risks for gastric cancers （adjusted OR, 1.32 and 95% CI, 0. 71 -2.36） in all subjects and with a significantly increased risks for gastric cancers in subjects with H. pylori infection （adjusted OR, 2.03 and 95% CI, 1.02 -4.80）. Conclusion The functional genetic polymorphisms of IL-IRN may contribute to the risks of gastric cancers in hlgh-risk population, particularly in those with H. pylori infection.