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Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer

Germline pathogenic and likely pathogenic (P/LP) variants in CHEK2 have been associated with increased prostate cancer (PrCa) risk. Our objective was to analyze their occurrence in Croatian PrCa men and to evaluate the clinical characteristics of P/LP variant carriers. Therefore, we analyzed CHEK2 i...

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Autores principales: Kirchner, Kira, Gamulin, Marija, Kulis, Tomislav, Sievers, Bianca, Kastelan, Zeljko, Lessel, Davor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689475/
https://www.ncbi.nlm.nih.gov/pubmed/36360192
http://dx.doi.org/10.3390/genes13111955
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author Kirchner, Kira
Gamulin, Marija
Kulis, Tomislav
Sievers, Bianca
Kastelan, Zeljko
Lessel, Davor
author_facet Kirchner, Kira
Gamulin, Marija
Kulis, Tomislav
Sievers, Bianca
Kastelan, Zeljko
Lessel, Davor
author_sort Kirchner, Kira
collection PubMed
description Germline pathogenic and likely pathogenic (P/LP) variants in CHEK2 have been associated with increased prostate cancer (PrCa) risk. Our objective was to analyze their occurrence in Croatian PrCa men and to evaluate the clinical characteristics of P/LP variant carriers. Therefore, we analyzed CHEK2 in 150 PrCa patients unselected for age of onset, family history of PrCa or clinical outcome, and the frequency of identified variants was compared to findings in 442 cancer-free men, of Croatian ancestry. We identified four PrCa cases harboring a P/LP variant in CHEK2 (4/150, 2.67%), which reached a statistical significance (p = 0.004) as compared to the control group. Patients with P/LP variants in CHEK2 developed PrCa almost 9 years earlier than individuals with CHEK2 wild-type alleles (8.9 years; p = 0.0198) and had an increased risk for lymph node involvement (p = 0.0047). No association was found between CHEK2 status and further clinical characteristics, including the Gleason score, occurrence of aggressive PrCa, the tumor or metastasis stage. However, carriers of the most common P/LP CHEK2 variant, the c.1100delC, p.Thr367Metfs15*, had a significantly higher Gleason score (p = 0.034), risk for lymph node involvement (p = 0.0001), and risk for developing aggressive PrCa (p = 0.027). Thus, in a Croatian population, CHEK2 P/LP variant carriers were associated with increased risk for early onset prostate cancer, and carriers of the c.1100delC, p.Thr367Metfs15* had increased risk for aggressive PrCa.
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spelling pubmed-96894752022-11-25 Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer Kirchner, Kira Gamulin, Marija Kulis, Tomislav Sievers, Bianca Kastelan, Zeljko Lessel, Davor Genes (Basel) Brief Report Germline pathogenic and likely pathogenic (P/LP) variants in CHEK2 have been associated with increased prostate cancer (PrCa) risk. Our objective was to analyze their occurrence in Croatian PrCa men and to evaluate the clinical characteristics of P/LP variant carriers. Therefore, we analyzed CHEK2 in 150 PrCa patients unselected for age of onset, family history of PrCa or clinical outcome, and the frequency of identified variants was compared to findings in 442 cancer-free men, of Croatian ancestry. We identified four PrCa cases harboring a P/LP variant in CHEK2 (4/150, 2.67%), which reached a statistical significance (p = 0.004) as compared to the control group. Patients with P/LP variants in CHEK2 developed PrCa almost 9 years earlier than individuals with CHEK2 wild-type alleles (8.9 years; p = 0.0198) and had an increased risk for lymph node involvement (p = 0.0047). No association was found between CHEK2 status and further clinical characteristics, including the Gleason score, occurrence of aggressive PrCa, the tumor or metastasis stage. However, carriers of the most common P/LP CHEK2 variant, the c.1100delC, p.Thr367Metfs15*, had a significantly higher Gleason score (p = 0.034), risk for lymph node involvement (p = 0.0001), and risk for developing aggressive PrCa (p = 0.027). Thus, in a Croatian population, CHEK2 P/LP variant carriers were associated with increased risk for early onset prostate cancer, and carriers of the c.1100delC, p.Thr367Metfs15* had increased risk for aggressive PrCa. MDPI 2022-10-27 /pmc/articles/PMC9689475/ /pubmed/36360192 http://dx.doi.org/10.3390/genes13111955 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 Brief Report
Kirchner, Kira
Gamulin, Marija
Kulis, Tomislav
Sievers, Bianca
Kastelan, Zeljko
Lessel, Davor
Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer
title Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer
title_full Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer
title_fullStr Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer
title_full_unstemmed Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer
title_short Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer
title_sort comprehensive clinical and genetic analysis of chek2 in croatian men with prostate cancer
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689475/
https://www.ncbi.nlm.nih.gov/pubmed/36360192
http://dx.doi.org/10.3390/genes13111955
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