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The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor

SIMPLE SUMMARY: Testicular cancer is the most common malignancy in the population of young and reproductively active men. The risk factors for its occurrence are not fully elucidated. Undescended testicle remains the main risk factor; however, more precise molecular studies associate genetic variati...

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Autores principales: Bumbasirevic, Uros, Bojanic, Nebojsa, Pljesa-Ercegovac, Marija, Zivkovic, Marko, Djukic, Tatjana, Zekovic, Milica, Milojevic, Bogomir, Kajmakovic, Boris, Janicic, Aleksandar, Simic, Tatjana, Coric, Vesna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870690/
https://www.ncbi.nlm.nih.gov/pubmed/35205816
http://dx.doi.org/10.3390/cancers14041068
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author Bumbasirevic, Uros
Bojanic, Nebojsa
Pljesa-Ercegovac, Marija
Zivkovic, Marko
Djukic, Tatjana
Zekovic, Milica
Milojevic, Bogomir
Kajmakovic, Boris
Janicic, Aleksandar
Simic, Tatjana
Coric, Vesna
author_facet Bumbasirevic, Uros
Bojanic, Nebojsa
Pljesa-Ercegovac, Marija
Zivkovic, Marko
Djukic, Tatjana
Zekovic, Milica
Milojevic, Bogomir
Kajmakovic, Boris
Janicic, Aleksandar
Simic, Tatjana
Coric, Vesna
author_sort Bumbasirevic, Uros
collection PubMed
description SIMPLE SUMMARY: Testicular cancer is the most common malignancy in the population of young and reproductively active men. The risk factors for its occurrence are not fully elucidated. Undescended testicle remains the main risk factor; however, more precise molecular studies associate genetic variations with susceptibility to testicular tumor development and progression. In this study, we found that specific variations in genes encoding antioxidant defense proteins confer risks of testicular cancer development and progression and, therefore, helps to identify subjects at higher risk, as well as those requiring additional diagnostics and more intensive forms of treatment. ABSTRACT: The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. NRF2 (rs6721961), GSTM3 (rs1332018), SOD2 (rs4880) and GPX3 (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant GPX3*TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant SOD2*TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined SOD2*TT/GPX3*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant GSTM3*AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease.
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spelling pubmed-88706902022-02-25 The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor Bumbasirevic, Uros Bojanic, Nebojsa Pljesa-Ercegovac, Marija Zivkovic, Marko Djukic, Tatjana Zekovic, Milica Milojevic, Bogomir Kajmakovic, Boris Janicic, Aleksandar Simic, Tatjana Coric, Vesna Cancers (Basel) Article SIMPLE SUMMARY: Testicular cancer is the most common malignancy in the population of young and reproductively active men. The risk factors for its occurrence are not fully elucidated. Undescended testicle remains the main risk factor; however, more precise molecular studies associate genetic variations with susceptibility to testicular tumor development and progression. In this study, we found that specific variations in genes encoding antioxidant defense proteins confer risks of testicular cancer development and progression and, therefore, helps to identify subjects at higher risk, as well as those requiring additional diagnostics and more intensive forms of treatment. ABSTRACT: The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. NRF2 (rs6721961), GSTM3 (rs1332018), SOD2 (rs4880) and GPX3 (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant GPX3*TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant SOD2*TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined SOD2*TT/GPX3*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant GSTM3*AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease. MDPI 2022-02-20 /pmc/articles/PMC8870690/ /pubmed/35205816 http://dx.doi.org/10.3390/cancers14041068 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bumbasirevic, Uros
Bojanic, Nebojsa
Pljesa-Ercegovac, Marija
Zivkovic, Marko
Djukic, Tatjana
Zekovic, Milica
Milojevic, Bogomir
Kajmakovic, Boris
Janicic, Aleksandar
Simic, Tatjana
Coric, Vesna
The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
title The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
title_full The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
title_fullStr The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
title_full_unstemmed The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
title_short The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
title_sort polymorphisms of genes encoding catalytic antioxidant proteins modulate the susceptibility and progression of testicular germ cell tumor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870690/
https://www.ncbi.nlm.nih.gov/pubmed/35205816
http://dx.doi.org/10.3390/cancers14041068
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