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 deletion status and UGT1A1*28 rs8175347 genotypes were assessed in 189 non-muscle-invasive bladder cancers (NMIBC) patients with pTa (77.2%) and pT1 (22.8%) tumors and a mean follow-up of 5.6 years, to investigate whether two common functional polymorphisms in GSTM1 and UGT1A1 genes and smoking history are associated with recurrence-free survival of patients with NMIBC.
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).
A significantly higher BC risk was associated with GSTM1 null genotype after adjusting to age, sex and smoking habit (OR 1.85, 95 % CI 1.30-2.62; P = 0.001).
After decades of research using a candidate gene approach, only NAT2 and GSTM1 have consistently been demonstrated to be germline genetic susceptibility markers for urinary bladder cancer (UBC).
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).
By combining relative risks and genotype frequencies we have computed theoretical attributable risks for lung and bladder cancers and the CYP1A1 Msp1, CYP1A1 Exon 7, GSTM1 and NAT2*5 genotypes, among Caucasians and among Asians.
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).