Metabolic Enzymes Gene Polymorphisms And BPDE-DNA Adducts With Lung Tumorigenesis

Objective Through investigating the effects of the relationship of CYP1A1,GSTM1genetic polymorphisms with BPDE-DNA adducts, to explore the mechanism of lung tumorigenesis.Methods The case control study included200cases of lung cancer and200controls. DNA were extracted from the blood samples of all subjects. The genotyping of both CYP1A1and GSTM1were detected by PCR-based restriction fragment length polymorphisms(PCR-RFLP), BPDE-DNA adducts was detected through competitive ELISA, and analyzed the data by chi-square test and logistic regression analysis. Results CYP1A1mutation genotype and GSTM1null genotype with smoke increased the risk of lung cancer, OR were2.406(1.321-4.382),2.755(1.470-5.163) respectively. The level of BPDE-DNA adducts in case was higher than in control, and the adducts level in ever smokers was higher than never smokers in200cases, the difference was statistically significant (P=0.0120). GSTM1null genotype individuals with BPDE-DNA leve1higher than5adducts/108nucleotide increased the risk of lung cancer (OR=1.988,95%CI:1.011-3.912); compared with never smokers with CYP1A1wild genotype, smokers with CYP1A1mutation genotype had an increased risk of forming a higher level of DNA adducts (P=0.0459);smokers with GSTM1null genotype formed more DNA adducts compared with never smokers with GSTM1function genotype (OR=2.432,95%CI:1.072-4.517). Conclusions CYP1A1mutation genotype and GSTM1null genotype may modify BPDE-DNA adduct levels then influenced the lung tumorigenesis and be useful biomarkers to identify individuals susceptible to lung cancer.