Interactive effect of genetic polymorphism of glutathione S-transferase M1 and smoking on squamous cell lung cancer risk in Korea.

To evaluate the role of the genetic polymorphisms of CYP2E1, GSTM1 and GSTT1, and their interaction with smoking in lung cancer development in Korean males, a hospital-based case-control study was conducted. Histologically confirmed male lung cancer patients (n=171) and male patients with no present or previous history of systemic illness who visited the urology department (n=196) were recruited from Seoul National University Hospital, Korea (1998-1999). CYP2E1 genotypes were determined by PCR-RFLP using RsaI digestion and GSTM1 and T1 genotypes were determined by multiplex PCR. Risks were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model adjusting for age and pack-year. Smoking was a significant risk factor for lung cancer (P<0.001). Although genetic polymorphisms of CYP2E1, GSTM1 and T1 were not associated with the overall risk of lung cancer, the GSTM1 null genotype significantly increased the risk of squamous cell lung cancer (OR=1.9, 95% CI=1.04-3.60). An interactive effect between the GSTM1 null genotype and smoking was observed (P=0.04). These results suggest that the GSTM1 null genotype is associated with squamous cell lung cancer and modifies the effect of smoking on squamous cell lung cancer development in Korean males.