Objective: Glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes are two xenobiotic metabolizing genes in Phase II of the detoxification process. The polymorphisms of GSTM1, GSTT1 genes, and smoking are involved in many cancers such as bladder cancer. Our aim was to assess the role of smoking status and GSTM1 and GSTT1 null genotypes in bladder cancer development in Algerian population.Methods: The current case–control study included 175 bladder cancer patients and 188 controls matched for age, gender, and ethnic origin. The GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction using blood genomic DNA. Possible associations of stage and grade with the obtained genotypes were also tested.Results: A significant associations were observed between bladder cancer risk and tobacco smoke (p value: p=1.21E-08), GSTM1 null genotype (p=0.018), GSTT1 null genotype (p=0.009), and GSTM1/GSTT1-double null genotype (p=0.001). The combined effect of smoking and testing deletions increased the risk of bladder cancer and the most important risk was observed among smokers carrying GSTM1/GSTT1-double null genotype (p=1.09E-05). No significant association was shown between stage and grade of bladder cancer and the testing genotypes.Conclusion: This study indicated that smoking, GSTM1 null, GSTT1 null, and GSTM1/GSTT1-double null genotypes individually represent a risk factor for bladder cancer in Algerian population. The interaction smoking gene increased the risk considerably. In fact, it is suggested that patients with cigarette smoking habit and combined GSTM1 and T1 genes deletion might be at increased risk of bladder cancer
