摘要目的 分析代谢酶基因细胞色素氧化酶P450(cytochrome P450,CYP450)1A1与谷胱苷肽硫转移酶M1(glutathione S-transferase μ1,GSTM1)的多态性和二羟环氧苯并芘(benzo A-pyrene-diolepoxide,BPDE)-DNA加合物之间的关系,并探讨其对肺癌发病的影响.方法 用病例-对照方法收集200例原发性肺癌患者的流行病学调查资料及外周血样本,采用限制性片段长度多态性-PCR法检测血中CYP1A1、GSTM1基因多态性,应用竞争性酶联免疫吸附法检测BPDE-DNA加合物浓度.结果 CYP1A1变异型吸烟者、GSTM1缺失型吸烟者患肺癌风险升高,OR值分别为2.406(1. 321～4. 382)和2.755(1.470～5.163).肺癌患者BPDE-DNA加合物浓度高于对照人群,且肺癌吸烟者加合物浓度明显高于肺癌不吸烟者(P=0.0252)；GSTM1缺失型个体DNA加合物水平高于5.0加合物/108核苷酸时,患肺癌的风险升高(OR=1.988,95％ CI:1.011～3.912)；CYP1A1变异型吸烟者形成高水平DNA加合物的风险明显高于CYP1A1野生型不吸烟者(P=0.0459); GSTM1缺失型吸烟者形成高水平DNA加合物的风险高于GSTM1功能型不吸烟者(OR=2.432,95％ CI:1.072～4.517).结论 GSTM1缺失型个体DNA加合物水平高更容易增加肺癌危险性；CYP1A1变异型吸烟者、GSTM1缺失型吸烟者更容易形成高水平的DNA加合物,对肺癌的发生可能有重要影响.

abstractsObjective To investigate the effect of CYP1A1 and GSTM1 genetic polymorphisms and BPDE-DNA adducts on lung tumorigenesis.Methods The case control study has included 200 cases of lung cancer and 200 controls.DNA was extracted from blood samples of all subjects.The genotype of both CYP1A1 and GSTM1 were detected with PCR-based restriction fragment length polymorphisms (PCRRELP).BPDE-DNA adducts were detected with competitive ELISA.Results CYP1A1 mutant genotype and GSTM1 null genotype with smoke has increased the risk of lung cancer,with OR being 2.406 (1.321-4.382),2.755(1.470-5.163),respectively.The level of BPDE-DNA adducts in patients was greater than control,and the adduct level in ever smokers was higher than never smokers,the difference was statistically significant (P=0.0252).GSTM1 null genotype individuals with BPDE-DNA level higher than 5 adducts/108 nucleotide have increased risk of lung cancer (OR=1.988,95％CI:1.011-3.912).Compared with never smokers with CYP1A1 wild genotype,smokers with CYP1A1 mutation genotype had an increased risk of forming a higher level of DNA adducts (P=0.0459).Smokers with GSTM1 null genotype formed more DNA adducts compared with never smokers with GSTM1 functional genotype (OR =2.432,95％ CI:1.072-4.517).Conclusion GSTM1 null genotype with higher level DNA adducts may increase the risk of lung cancer. DNA adducts form easier in smokers with CYP1A1 mutation genotype and GSTM1 null genotype,which in turn may influence lung tumorigenesis.