Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis

Abstract

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs’ role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.