CYP2E1、GSTT1基因多态性与胃癌易感性的关系

Relationship Between CYP2E1,GSTT1 Genetic Polymorphisms and Susceptibility to Gastric Cancer

目的探讨 CYP2 E1、GSTT1基因多态性与胃癌遗传易感性的可能关系。方法运用病例 -对照分子流行病学研究方法和聚合酶链反应技术对胃癌病例组和正常对照组基因组 DNA进行 CYP2 E1、GSTT1基因分型。结果 Rsa 酶切的 CYP2 E1各基因型在胃癌病例组与对照组间的分布频率分别为 A(c1/ c1)型 71.1%、5 2 .2 % ,B(c1/ c2 )型 2 4 .4 %、4 3.3% ,C(c2 / c2 )型 4 .4 %、4 .4 % ,分布差异有显著性 (χ2 =7.34,P=0 .0 2 5 ) ,A型基因使胃癌发生的危险性增加 (OR=2 .2 5 ,95 % CI=1.16～ 4 .37) ;c1等位基因在病例中的分布频率为 83.3% ,显著高于对照 (73.9% ) (χ2 =4 .77,P=0 .0 2 8)。胃癌组 GSTT1空白基因型 (null)频率 (6 0 .0 % )显著高于对照 (4 3.3% ,χ2 =5 .0 1,P=0 .0 2 5 ) ,GSTT1基因缺失增加胃癌发生的危险性 (OR=1.96 ,95 % CI为 1.0 4～ 3.71)。按 GSTT1基因存在与否分层分析发现 ,当 GSTT1基因存在时 ,CYP2 E1基因多态性与胃癌发生未见显著关联 ,而在 GSTT1基因缺失组 ,CYP2 E1A(c1/ c1)基因型者发生胃癌的危险性显著增加。CYP2 E1A(c1/ c1)且 GSTT1(null)型个体患胃癌的危险性是 CYP2 E1B(c1/ c2 ) / C(c2 / c2 )且 GSTT1(nonnull)个体的 3.71倍 (95 % CI=1.5 4～ 8.94 )。结论 CYP2 E1、GSTT1基?

Objective To examine the association between genetic polymorphisms of CYP2E1,GSTT1 and susceptibility of gastric cancer.Methods A case-control study and polymerase chain reactions(PCR) technique were used to identify CYP2E1,GSTT1 genotype in 90 cases of primary gastric cancer and 90 controls.Results The frequencies of CYP2E1 genotypes detected by RsaⅠ digestion in cases and controls were 71.1%,52.2% for A(c1/c1),24.2%,43.3% for B(c1/c2)and 4.4%,4.4% for C(c2/c2) respectively.There were significant differences in frequencies of genotypes between the two groups(χ 2=7.34,P=0.025).Genotype A(c1/c1) correlated with the susceptibility to gastric cancer(OR=2.25,95%CI=1.16~4.37).The frequency of cl allele was significantly higher in the patients(83.3%) than in the controls(73.9%)(χ 2=4.77,P=0.028).The distribution of frequency of GSTT1 null genotype was found to be significantly different between the patients(60.0%) and controls(43.3%).Individuals with GSTT1 null genotype were at a 1.96 folds(95% CI=1.04~3.71) increased risk of developing gastric cancer.When subjects were categorized by GSTT1 genotype,the association between the genetic polymorphism of CYP2E1 and susceptibility to gastric cancer wasn't found in those carrying GSTT1 nonnull genotype,but it existed in those with GSTT1 null genotype.The risk for gastric cancer in those with CYP2E1 A(c1/c1) and GSTT1 null genotype was significantly higher than that in those with CYP2E1 B(c1/c2)/C (c2/c2) and GSTT1 nonnull genotype(OR=3.71,95%CI=1.54~8.94).Conclusions The genetic polymorphisms of CYP2E1,GSTT1 were associated with the genetic susceptibility.GSTT1-null genotype was associated with the risk for gastric cancer.There existed an interaction in gastric cancer between CYP2E1 and GSTT1.