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).
GSTM1-negative, GSTT1-positive, and hOGG1 Ser326Ser and Ser326Cys genotypes are risk factors for bladder cancer (P = 0.020, P = 0.044, and P = 0.012, respectively).
GSTM1, GSTT1 and GSTP1 genotype frequencies were determined in bladder cancer cases (n=72) and healthy controls with no history of malignancies (n=82) using PCR-based techniques.
A greater reduction in bladder cancer risk was observed among current-smokers (OR: 0.43; 95% CI: 0.27-0.71) and carriers of GSTM1-null (homozygous absence) genotypes (OR: 0.43; 95% CI: 0.22-0.85).
Among the low-penetrant genes, the variants within the genes encoding metabolic enzymes have been consistently associated with susceptibility to bladder cancer and the evidence is compelling for NAT2 slow acetylator and GSTM1 null genotypes.
Among women, the GSTM1 null genotype was associated with an elevated bladder cancer risk only among smokers (OR 2.3; 95% CI 1.1-4.5 in ever smokers versus OR 0.9; 95% CI 0.3-2.5 in never smokers).
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).
Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk.
Besides, meaningful association between individuals who carried the GSTM1 null genotype and increased BCa risk was detected (OR = 1.39, 95%CI 1.28-1.51).
Combination of the high-risk genotypes (GSTM1 null + GSTT1 null + GSTP1 313 A/G or G/G) demonstrated further increase in the BC risk (OR = 6.64, 95 %CI = 3.63-12.16).
Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively).