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).
Therefore, the degree to which rs9642880[T] and GSTM1 0/0 confer susceptibility to urinary bladder cancer seems to depend on the extent of exposure to urinary bladder carcinogens.
Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies.
The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes).
When the OR used to determine statistical power was lowered to 1.2, 2 of the 4 noteworthy associations remained so: GSTM1 null with bladder cancer and acute leukemia.
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.
Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02).
This study suggests that in Korean subjects the GSTM1 null genotype may be associated with increased risk for bladder cancer, in a manner that appears to depend upon smoking status.
Our data strongly support that high vegetable consumption, especially cruciferous vegetable intake, may protect against bladder cancer and that genetic variants of GSTM1 and NAT2 may modify the association.
These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population.
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).
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).
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).
We investigated the genotype and expression of glutathione S-transferase-mu (GSTM1) and glutathione S-transferase-theta (GSTT1) in BC tissue specimens.
Likewise, analyses of the NAT1 and glutathione S-transferase mu 1 (GSTM1) genotypes showed no associations between the NAT1 or GSTM1 genotypes and bladder cancer risk.
Thus, a hospital-based case-control study was performed with 296 patients with bladder cancer and 400 controls, investigating this GSTM1 deficiency in relation to environmental risk factors and types of bladder cancer.
Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004).
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).