CYP1A1和CYP2E1基因多态与胃癌易感性关系的研究

Research on Association of Genetic Polymorphism of CYP1A1 and CYP2E1, with Susceptibility to Gastric Cancer

摘要: 目的：探讨细胞色素P450 (CYP450)基因CYP1A1第7外显子的Ile462Val (rs1048943)以及CYP2E1-1239G>C (rs3813867)单核苷酸多态(SNP)与胃癌遗传易感性的相关关系。方法：采用病例–对照研究，聚合酶链反应–限制性片断长度多态性分析(PCR-RFLP)方法，分析230例胃癌患者和460例正常对照者的CYP1A1基因Ile462Val以及CYP2E1基因-1239G>C位点的基因型。以比值比(OR)及其95％可信区间(CI)比较不同基因型与胃癌发病风险的相关关系。结果：与CYP1A1 462 Ile/Ile基因型携带者相比，462 Val/Val基因型携带者胃癌发病风险显著降低，其OR值分别为0.31 (95% CI: 0.16 − 0.60; P = 0.001)。吸烟分层分析显示，在吸烟人群中，至少携带一个462Val等位基因的基因者与未携带者相比，发生胃癌的风险显著降低了59% (OR = 0.41, 95%CI = 0.24 − 1.43; P = 0.001)；且这种保护作用在重度吸烟患者中尤为明显(OR = 0.29, 95% CI = 0.14 − 0.64; P = 0.002)。而CYP2E1-1239G>C各基因型分布在正常人群和胃癌患者中差异无统计学意义(P > 0.05)。CYP1A1基因Ile462Val变异是影响胃癌易感性的重要因素。

Abstract: Objective: To investigate the association of CYP1A1 Ile462Val and CYP2E1-1239G>C polymor-phisms with gastric cancer (GC) in Chinese population. Methods: The study included 230 cases with GC and 460 frequency-matched controls. The polymerase chain reaction-restriction frag-ment length polymorphism (PCR-RFLP) method was used to analyze genotype CYP1A1 Ile462Val and CYP2E1-1239G>C polymorphisms. The odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression model. Results: Compared with the CYP1A1 462 Ile/Ile genotype carriers, the subjects with 462 Val/Val genotype carriers have de-creased risk for gastric cancer, with the 0.31 of OR and 0.16 - 0.60 of 95% CI. When stratified by smoking status, subjects with at least one 462Val allele carrier had a reduced risk of developing GC (OR = 0.29, 95% CI = 0.14 - 0.64) among heavy smokers, but not among non-smokers. There was no significant difference in CYP2E1-1239G>C genotype distribution between gastric cancer cases and the control. Conclusion: CYP1A1 Ile462Val polymorphism is associated with the sus-ceptibility to GC in Chinese population.