Objective: To investigate the relationship between the gene polymorphism of metabolizing enzymes and the genetic susceptibility to lung cancer as well as to study the synergistic effects between smoking and the genes.
Methods: Peripheral blood samples were collected from 279 patients with primary lung cancer and 684 age-, nationality-, and native place-matched controls, including patients with benign diseases and healthy volunteers. PCR-RELP was used to detect the distribution of CYP1A1, 2D6, 2E1, and GSTM1 genotypes. The correlation of these genes with the sensibility to lung cancer was analyzed.
Results: The CYP1A1 variant allele frequency of the lung cancer group was 67.4%, significantly higher than that of the control group (55.7%, P = 0.001). GSTM1-null genotype was found to be associated with lung cancer (OR = 1.58, P = 0.002). The risk of lung cancer in the individuals carrying GSTM1-null genotype and CYP1A1 (w/m, m/m) genotype was 2.75 times that of the individuals not carrying these genotypes (P < 0.01). There were no significant differences in the frequencies of CYP2D6 and CYP2E1 genotypes between these two groups. In the heavy smokers GSTM1-null, CYP1A1, CYP2D6, and CYP2E1 genotypes increased the risk of lung cancer by 5.71 - 11.67 times (P = 0.000).
Conclusion: The individuals who carry GSTM1-null genotype and CYP1A1 (m) genotype have an increase risk of lung cancer. The combined effect of I phase metabolizing enzymes and II phase metabolizing enzymes is observed. In heavy smokers the polymorphism of GSTM1 and CYPs affects the susceptibility to lung cancer.