Dataset Information

The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study.

ABSTRACT: Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of GSTO1rs4925, GSTO2rs156697, and GSTO2rs2297235 polymorphisms with the risk for testicular GCT development, in 88 patients and 96 matched controls, through logistic regression models. We found that carriers of the GSTO1*C/A*C/C genotype exhibited an increased risk for testicular GCT development. Significant association with increased risk of testicular GCT was observed in carriers of GSTO2rs2297235*A/G*G/G genotype, and in carriers of combined GSTO2rs156697*A/G*G/G and GSTO2rs2297235*A/G*G/G genotypes. Haplotype H7 (GSTO1rs4925*C/GSTO2rs2297235*G/GSTO2rs156697*G) exhibited higher risk of testicular GCT, however, without significant association (p > 0.05). Finally, 51% of testicular GCT patients were the carriers of all three risk-associated genotypes, with 2.5-fold increased cumulative risk. In conclusion, the results of this pilot study suggest that GSTO polymorphisms might affect the protective antioxidant activity of GSTO isoenzymes, therefore predisposing susceptible individuals toward higher risk for testicular GCT development.

SUBMITTER: Petrovic M

PROVIDER: S-EPMC10301167 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study.

Petrovic Milos M Simic Tatjana T Djukic Tatjana T Radic Tanja T Savic-Radojevic Ana A Zekovic Milica M Durutovic Otas O Janicic Aleksandar A Milojevic Bogomir B Kajmakovic Boris B Zivkovic Marko M Bojanic Nebojsa N Bumbasirevic Uros U Coric Vesna V

Life (Basel, Switzerland) 20230527 6

Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of GSTO1rs4925, GSTO2r ...[more]

PMID: 37374052

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Project description:Cancer-testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis-specific expressed protein-coding genes and 863 testis-specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein-coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10-13 ) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = -0.28, P = 1.20 × 10-3 ). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down-regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up-regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease-free interval and progression-free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT.

Dataset Information

The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study.

Publications

The Polymorphisms in <i>GSTO</i> Genes (<i>GSTO1</i> rs4925, <i>GSTO2</i> rs156697, and <i>GSTO2</i> rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study.

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