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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

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2023
life-13-01269.pdf (500.4Kb)
Authors
Petrović, Miloš
Simić, Tatjana
Đukić, Tatjana
Radić, Tanja
Savić-Radojević, Ana
Zeković, Milica
Durutović, Otaš
Janičić, Aleksandar
Milojević, Bogomir
Kajmaković, Boris
Živković, Marko
Bojanić, Nebojša
Bumbaširević, Uroš
Ćorić, Vesna
Article (Published version)
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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.

Keywords:
testicular GCT / glutathione transferase / GSTO / gene polymorphism / oxidative stress
Source:
Life, 2023, 13, 6, 1269-
Publisher:
  • Multidisciplinary Digital Publishing Institute (MDPI)
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200110 (University of Belgrade, Faculty of Medicine) (RS-200110)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200015 (University of Belgrade, Institute for Medical Research) (RS-200015)

DOI: 10.3390/life13061269

ISSN: 2075-1729

[ Google Scholar ]
URI
http://rimi.imi.bg.ac.rs/handle/123456789/1304
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
Institut za medicinska istraživanja
TY  - JOUR
AU  - Petrović, Miloš
AU  - Simić, Tatjana
AU  - Đukić, Tatjana
AU  - Radić, Tanja
AU  - Savić-Radojević, Ana
AU  - Zeković, Milica
AU  - Durutović, Otaš
AU  - Janičić, Aleksandar
AU  - Milojević, Bogomir
AU  - Kajmaković, Boris
AU  - Živković, Marko
AU  - Bojanić, Nebojša
AU  - Bumbaširević, Uroš
AU  - Ćorić, Vesna
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1304
AB  - 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.
PB  - Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Life
T1  - The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study
IS  - 6
SP  - 1269
VL  - 13
DO  - 10.3390/life13061269
ER  - 
@article{
author = "Petrović, Miloš and Simić, Tatjana and Đukić, Tatjana and Radić, Tanja and Savić-Radojević, Ana and Zeković, Milica and Durutović, Otaš and Janičić, Aleksandar and Milojević, Bogomir and Kajmaković, Boris and Živković, Marko and Bojanić, Nebojša and Bumbaširević, Uroš and Ćorić, Vesna",
year = "2023",
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.",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Life",
title = "The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study",
number = "6",
pages = "1269",
volume = "13",
doi = "10.3390/life13061269"
}
Petrović, M., Simić, T., Đukić, T., Radić, T., Savić-Radojević, A., Zeković, M., Durutović, O., Janičić, A., Milojević, B., Kajmaković, B., Živković, M., Bojanić, N., Bumbaširević, U.,& Ćorić, V.. (2023). The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study. in Life
Multidisciplinary Digital Publishing Institute (MDPI)., 13(6), 1269.
https://doi.org/10.3390/life13061269
Petrović M, Simić T, Đukić T, Radić T, Savić-Radojević A, Zeković M, Durutović O, Janičić A, Milojević B, Kajmaković B, Živković M, Bojanić N, Bumbaširević U, Ćorić V. The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study. in Life. 2023;13(6):1269.
doi:10.3390/life13061269 .
Petrović, Miloš, Simić, Tatjana, Đukić, Tatjana, Radić, Tanja, Savić-Radojević, Ana, Zeković, Milica, Durutović, Otaš, Janičić, Aleksandar, Milojević, Bogomir, Kajmaković, Boris, Živković, Marko, Bojanić, Nebojša, Bumbaširević, Uroš, Ćorić, Vesna, "The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study" in Life, 13, no. 6 (2023):1269,
https://doi.org/10.3390/life13061269 . .

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