Genetic polymorphism of glutathione S-transferases M1 and T1 as a risk factor in lung and bladder cancers

A combined analysis of two polymorphic enzymes, glutathione S-transferase m u (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a mult iplex polymerase chain reaction (PCR) based method, the frequency of the ho mozygous deleted GSTM 1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sam ple of 248 healthy, unrelated individuals. In both cancer groups the freque ncy of the GSTM1 null genotype was higher in comparison with that of the co ntrol group (59% and 59.7% vs. 49.6%), but this increase did not reach stat istical significance (p > 0.05). After grouping by the smoking status, amon g smokers in both cancer groups (62.1% in lung cancer and 71.4% in the blad der cancer group, respectively) there were statistically significantly p < 0.05) increased frequencies of the GSTM1 deletion genotype as compared to t he control group (49.6%). Smokers with absence of the GSTM 1 gene were at a n approximately 1.7-fold higher risk for lung cancer (odds ratio - OR= 1.67 , 95% confidence interval - CI 95% = 1.0-2.7,p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR= 2.54, CI 95% = 1.2-5.5, p = 0 .02). As related to GSTT1, our study demonstrated an overall GSTT1 effect o n bladder cancer risk. Individuals with absence of the GSTT1 gene were at a n approximately 2.5-fold higher risk of developing bladder cancer. In the l ung cancer cases, the frequency of the putatively high risk GSTT1 null geno type was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 geno type. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because t hey lack both enzymes. The findings suggest that the GSTM 1 null genotype m ay be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the G STT1 null genotype is not a critical factor in mediating the risk of lung c ancer, but may be associated with an increased susceptibility to bladder ca ncer.