The role of N-acetyltransferase-2 and glutathione S-transferase on the risk and aggressiveness of bladder cancer.

N-acetyltransferase-2 (NAT-2) and Glutathione-S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphism have been implicated in the detoxification of urothelial carcinogens, such as arylamines and polycyclic aromatic hydrocarbons. The results of epidemiological studies examining the role of NAT-2, GSTM1 and GSTT1 genotypes on the risk factors for bladder cancer were controversial, although suggesting that there may be an increased risk of the disease associated with these genotypes. The aim of the present study was to examine the independent effect and a possible interaction of NAT-2, GSTM1 and GSTT1 genotypes on the risk of bladder carcinogenesis, in the frame of a case-control study. We also investigated the possible association of specific genotype combinations with more aggressive disease in terms of tumor grading and local staging at the time of initial diagnosis. Between August 1996 and May 1998, 89 newly-diagnosed bladder cancer patients (transitional cell type) and 147 controls were included in the study. All patients were selected at the time of first diagnosis, done in the Department of Urology at the University Hospital of Ioannina, in north-western Greece. GSTM1 and NAT-2 deficient genotypes were found to be independently associated with the risk of bladder cancer (odds ratios 2.87 and 2.64, respectively). The GSTT1 genotype did not present any significant association with bladder cancer risk. We did not find a significant interaction between genotypes. These results could be explained by the independent activity of the two enzymes. Studies that will simultaneously examine the role of several genetic and environmental factors involved in bladder carcinogenesis are needed to give a global picture for the risk factors of bladder cancer and their potential interaction.