Association of glutathione transferase omega polymorphisms with risk and survival in transitional cell carcinoma of urinary bladder

Abstract

Exposure to chemical carcinogens, especially smoking and occupational exposure, is an etiologic factor for transitional cell carcinoma (TCC) of the urinary bladder. Cytosolic glutathione transferases (GSTs) are a superfamily of enzymes that protect normal cells by catalyzing conjugation reactions of electrophilic compounds, including carcinogens, to glutathione. Several types of allelic variations have been identified within GSTO class, with GSTO1*A140D (NCBI SNP ID: rs4925, 419 C to A) and GSTO2*N142D (NCBI SNP ID: rs156697, 424 A to G) being the most common. Individuals with the GSTO2*G/G genotype carry a higher risk for TCC. Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased TCC risk, which is more pronounced in carriers of variant GSTO2*G/G combined with smoking. Furthermore, GSTO1*A/A and GSTO2*G/G genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive TCC. Newly discovered deglutathionylase activity of GSTO1 suggests its potential important role in redox perturbations present in TCC, which might contribute to progression of TCC.