Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784656818247565312 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8870690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bumbasirevicuros thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT bojanicnebojsa thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT pljesaercegovacmarija thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT zivkovicmarko thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT djukictatjana thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT zekovicmilica thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT milojevicbogomir thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT kajmakovicboris thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT janicicaleksandar thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT simictatjana thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT coricvesna thepolymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT bumbasirevicuros polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT bojanicnebojsa polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT pljesaercegovacmarija polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT zivkovicmarko polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT djukictatjana polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT zekovicmilica polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT milojevicbogomir polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT kajmakovicboris polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT janicicaleksandar polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT simictatjana polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor AT coricvesna polymorphismsofgenesencodingcatalyticantioxidantproteinsmodulatethesusceptibilityandprogressionoftesticulargermcelltumor |