Polymorphisms in GSTM1, CYP1A1, CYP2E1, and CYP2D6 are Associated with Susceptibility and Chemotherapy Response in Non-small-cell Lung Cancer Patients

Studies of polymorphisms in CYP1A1, CYP2E1, CYP2D6, and GSTM1 and their relationship to lung cancer susceptibility and chemotherapy response have been reported, but the results are not consistent. In this study we selected four polymorphisms in these genes, several of which have previously been researched, and investigated their association with lung cancer susceptibility and chemotherapy response. We genotyped the four polymorphisms in a cohort composed of 217 non-small-cell lung cancer (NSCLC) patients and 198 controls. Of these, 145 advanced NSCLC patients underwent chemotherapy and were monitored for 5 years. Significant differences in the GSTM1 polymorphism were observed between the case and control groups (P = 0.02). We observed a synergistic effect of smoking and GSTM1. Smokers with deficient-type GSTM1 had a 4.96-fold increased risk of developing lung cancer. Significant differences in GSTM1 and CYP1A1 polymorphisms were observed between the response and nonresponse groups (P = 0.004 and P = 0.026). Moreover, patients with deficient-type GSTM1 were superior responders to platinum drugs than those carrying wild-type GSTM1 (P = 0.014). In addition, patients carrying TT CYP1A1 responded better to nonplatinum drugs than those carrying TC and CC CYP1A1 (P = 0.01). Polymorphisms in the four enzymes had no effect on the overall survival of NSCLC patients. Our findings support the hypothesis that a polymorphism in GSTM1 is associated with lung cancer susceptibility. Furthermore, polymorphisms in GSTM1 and CYP1A1 were associated with chemotherapy response. In particular, smokers carrying deficient-type GSTM1 were at a higher risk of developing lung cancer. Patients carrying deficient-type GSTM1 responded better to platinum drugs, while those with TT CYP1A1 were better responders to nonplatinum drugs.