CYP1A1、GSTM1基因多态性与食管癌遗传易感性

Case-control study on relationship of CYP1A1 and GSTM1 polymorphisms and susceptibility to esophageal squamous carcinoma

目的探讨细胞色素氧化酶P450(CYP)1A1、谷胱苷肽硫转移酶(GSTM1)的基因多态性与食管癌遗传易感性关系,以及基因基因、基因环境之间的交互作用。方法收集新发食管癌患者89例(病例组)及同期非食管疾患患者98例(对照组),调查与食管癌相关的危险因素;基因多态性检测采用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)方法;比较病例组和对照组CYP1A1的MspI多态、Ile/Val多态和GSTM1基因多态性的分布情况,并结合环境因素进行单因素、多因素Logistic回归分析以及联合作用分析。结果MspI多态的突变型杂合子m1/m2(基因型B)和突变型纯合子m1/m2(基因型C)在病例组与对照组的分布差异有统计学意义,ORB值为1.93(95%CI=1.01～3.84),ORC值为3.62(95%CI=1.61～8.14),Ile/Val多态的突变型和GSTM1缺失型在两组的分布差异无统计学意义;MspI多态的突变型和GSTM1缺失型对食管癌发生的交互作用差异有统计学意义,OR值为3.57(95%CI=1.36～9.41);MspI多态的突变型与摄入较多新鲜蔬菜水果和蛋类呈拮抗作用,联合作用指数(S)分别为0.26和0.48,MspI多态的突变型与食管癌家族史呈协同作用,S为2.36。结论MspI多态的突变型与食管癌易感性有关,它与摄入较多新鲜蔬菜水果和蛋类及食管癌家族史对食管癌的发生存在交互作用;

Objective To study the relationship of the genetic polymerphisms of CYP1A1 and GSTM1 and susceptibility to esophageal squamous cell carcinoma (ESCC) and the gene-gene and gene-environment interaction.Methods A case control study which included 89 cases of esophageal cancer and 98 controls collected from the ChangZhi HePing Hospital and the ChangZhi HeJi hospital.All subjects were investigated with a uniform questionnaire.Genotyping of both CYP1A1 and GSTM1 were detected in blood samples of all subjects by PCR and PCR-RELP.Cobined genetic factors with environmental factors,the interaction of gene-gene and gene-environment was analyzed.Results Only CYP1A1 Msp I mutation genotype showed significant difference between the two groups,with an OR_B of 1.93(95%CI=1.01～3.84),with an OR_C of 3.62(95% CI=1.61～8.14).There were on signoficant differences in the frequency distribution of three genotypes of CYP1A1 Ile-Val polymorphisms and GSTM null genotype between ESCC patients and controls.Combined effects of the CYP1A1 Msp I mutation genotype,and GSTM1 mull genotype indicated a notable interaction for increasing the regression genotype and GSTM1 mull genotype indicated a notable interaction for increasing the risk of ESCC,with an OR of 3.57(95%CI=1.36～9.41).No significant interaction was observed between the mutation genotype of CYP1A1 Ile-Val polymorphism and GSTM1 null genotype.Multiple Logistic regression models showed that CYP1A1 Msp I mutation genotype and family history of esophageal cancer(EC) were significant risk factors in genetic.The analytical results of combined effects showed that the effects of taking in fresh vegetable and fruit and eggs and CYP1A1 Msp I mutation genotype were resistant (s=0.26;s=0.48 respectively),The combined effects between family history of EC and CYP1A1 Msp I mutation genotype were synergistic (s=2.36).Conclusion CYP1A1 Msp I polymorphisms was susceptible to ESCC.Combined effects of the CYP1A1 Msp I mutation genotype with family history of EC were synergistic.Subjects with either CYP1A1 Msp I mutation genotype or family history of EC were the higher risk population of ESCC,and more attentions should be paid to in the carcinoma control program.