We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC).
In conclusion, the GSTM1-null, GSTT1-null and dual-null GSTM1-GSTT1 genotypes might be associated with the onset of bladder cancer, but additional genetic-epidemiological studies should be conducted to explore this association further.
With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs).
The common deletion of the glutathione S-transferase Mu 1 (GSTM1) gene in humans has been shown to be involved in xenobiotic metabolism and associated with bladder cancer.
The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped.
Stratified analyses of population-based associations indicated increased bladder cancer risk associated with GSTM1-null and GSTM1/GSTT1 double-null genotypes in hospital-based and population-based studies.
The most relevant polymorphisms for occupational bladder cancer risk were GSTM1 and UGT1A, especially when co-occurring (GSTM1 negative and rs11892031[A/A]: 48% cases vs. 38% controls, OR 1.47, 95% CI 0.99-2.20).
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).
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.
There was no association between bladder cancer and GSTM1 polymorphism (ORs = 0.64, 95% CI = 0.32-1.29), but the probability of bladder cancer in patients with GSTT1 null genotype (67.9%), was significantly higher from the probability of bladder cancer with GSTT1 normal genotype (43.0%) statistically (ORs = 2.8, 95% CI = 1.16-6.75).
Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ≤ .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03).
The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001).
The cumulative meta-analyses showed a trend of more obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population as data accumulated by year.
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).
These findings suggest that seven bladder cancer risk-associated variants (rs9642880, rs2294008, rs798766, rs1495741, GSTM1 null, rs17674580 and rs10936599) may be used, collectively, to effectively measure inherited risk for bladder cancer.
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).
Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.
The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance.