Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004).
The overall odds ratio for bladder cancer with the GSTM1 null genotype was 1.4 (95% confidence interval 0.94-2.1), indicating no statistical difference in null genotype frequencies among bladder cancer patients compared to a healthy population.
Our results offer one explanation for the recent findings that GSTM1 polymorphism is a risk modifier in smoking-related cancers, especially bladder cancer.
Thus, a hospital-based case-control study was performed with 296 patients with bladder cancer and 400 controls, investigating this GSTM1 deficiency in relation to environmental risk factors and types of bladder cancer.
Thus, our results suggest that GSTM1 is involved in the detoxification of 3- and 4-ABP and may contribute to the racial variation in bladder cancer incidence among white, black, and Asian males in Los Angeles, CA.
An elevated relative bladder cancer risk of GSTM1 null genotype carriers was indicated by comparison of this background with the data of the bladder cancer cases (OR = 1.81; 95% CI [1.10, 2.98]; p = 0.019).
Thus, in this study, the GSTM1 deletion is not a risk factor for the development of bladder cancer, but may be related to the survival of the bladder cancer patients.
Our results indicate that the frequency of bladder cancer patients with the GSTM1 null genotype is significantly higher than that of the normal controls (86.3 and 47.6%, respectively) with an odds ratio (OR) of 6.97 (95% CL -1.59-30.57, Fisher's exact P = 0.008).
In conclusion, molecular genetic analysis of a large sample specified the increased bladder cancer risk of those who are deficient in NAT2 and GSTM1; the other traits proved to be of minor impact.
These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population.
Likewise, analyses of the NAT1 and glutathione S-transferase mu 1 (GSTM1) genotypes showed no associations between the NAT1 or GSTM1 genotypes and bladder cancer risk.
Numerous studies have shown that glutathione S-transferase M1 deficiency (GSTM1*0/0) increases the risk for lung and bladder cancer but the overall risk attributable to GSTM1*0/0 was only around 1.3 according to meta-analyses.
Previous studies have correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancer, in heavy smokers.
In conclusion, our results indicate that the null genotypes for GSTM1 and GSTT1, either individually or in combination, are important host risk factors for bladder cancer.
Smokers with absence of the GSTM1 gene were at an 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).
These findings suggest that specific single polymorphic GST genes, that is GSTM1 in the case of bladder cancer and GSTT1 in the case of prostatic carcinoma, are most relevant for the development of these urological malignancies among the general population in Central Europe.