AUTHOR=Santric Veljko , Dragicevic Dejan , Matic Marija , Djokic Milica , Pljesa-Ercegovac Marija , Radic Tanja , Suvakov Sonja , Nikitovic Marina , Stankovic Vesna , Milojevic Bogomir , Radovanovic Milan , Dzamic Zoran , Simic Tatjana , Savic-Radojevic Ana 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.620690

DOI=10.3389/fmolb.2021.620690

ISSN=2296-889X

ABSTRACT=<p>Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in <italic>GSTO1</italic> and <italic>GSTO2</italic> might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of <italic>GSTO1</italic> and <italic>GSTO2</italic> 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 (<italic>GSTM1</italic>, <italic>GSTT1</italic>, and <italic>GSTP1</italic>). 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 <italic>GSTO1</italic>*A/A and <italic>GSTO2</italic>*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both <italic>GSTO1</italic>*A and <italic>GSTO2</italic>*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 (<italic>GSTM1</italic>, <italic>GSTT1</italic>, and <italic>GSTP1</italic>) in terms of PC prognosis has shown shorter survival in carriers of <italic>GSTP1</italic>*T/T (<italic>rs1138272</italic>) genotype than in those carrying at least one referent allele. In addition, the presence of <italic>GSTP1</italic>*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.</p>