Genetic Polymorphisms of Genes Gstm1 and Cyp2d6 and Bladder Cancer

Objective: To study the relationship between GSTM1 and CYP2D6 polymorphisms and exposure to risk factors, and the occurrence of bladder cancer. Patients and Methods: The study included 77 patients with fully characterized transitional cell carcinoma of the bladder, from whom a complete history was taken, and 191 healthy individuals, who served as controls for the genetic assessment. Using a polymerase chain reaction technique, GSTM1 polymorphisms were studied in all patients and controls, and CYP2D6 polymorphisms were studied in 53 patients and 99 controls. Chi-squared test was used for statistical analysis. Results: GSTM1 null genotype was detected in 75.3% of patients and in 57.1% of controls, and the difference was statistically significant (χ = 7.79; p = 0.005). This difference was due exclusively to individuals with tumors Ta/T1 (81.5% were GSTM1 deficient, χ = 10.7; p = 0.001). More smokers (85.7%) than nonsmokers (62.8%) demonstrated the GSTM1 null phenotype (χ = 5.36; p = 0.02), and 95.8% of heavy smokers (> 40 pack-year) were GSTM1 null. Familial history of tumors was associated with GSTM1 null: 91.7% of patients with familial history versus 67.9% without such history showed the null phenotype (χ = 5.01; p = 0.02). Patients and controls were not significantly different in respect to frequency of CYP2D6 polymorphisms. Among patients, no significant association between CYP2D6 polymorphisms and tumor characteristics was found. Conclusions: GSTM1 null genotype seems to be associated with bladder tumor occurrence, particularly “superficial” tumors (Ta/T1). This association is stronger in individuals with exposure to tobacco smoke. CYP2D6 gene does not seem to play any significant role in bladder tumor development.