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Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors
Testicular germ cell tumors (TGCTs) represent the most frequent malignancy in young adult men and have one the highest heritability rates among all cancers. A recent multicenter case–control study identified CHEK2 as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed CHEK2 in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672725/ https://www.ncbi.nlm.nih.gov/pubmed/38002677 http://dx.doi.org/10.3390/jcm12227065 |
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author | Kirchner, Kira Seidel, Christoph Paulsen, Finn-Ole Sievers, Bianca Bokemeyer, Carsten Lessel, Davor |
author_facet | Kirchner, Kira Seidel, Christoph Paulsen, Finn-Ole Sievers, Bianca Bokemeyer, Carsten Lessel, Davor |
author_sort | Kirchner, Kira |
collection | PubMed |
description | Testicular germ cell tumors (TGCTs) represent the most frequent malignancy in young adult men and have one the highest heritability rates among all cancers. A recent multicenter case–control study identified CHEK2 as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed CHEK2 in 129 TGCT cases unselected for age of onset, histology, clinical outcome, and family history of any cancer, and the frequency of identified variants was compared to findings in 27,173 ancestry-matched cancer-free men. We identified four TGCT cases harboring a P/LP variant in CHEK2 (4/129, 3.10%), which reached statistical significance (p = 0.0191; odds ratio (OR), 4.06; 95% CI, 1.59–10.54) as compared to the control group. Cases with P/LP variants in CHEK2 developed TGCT almost 6 years earlier than individuals with CHEK2 wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between CHEK2 status and further clinical and histopathological characteristics, including histological subtypes, the occurrence of aggressive TGCT, family history of TGCT, and family history of any cancer. In addition, we found significant enrichment for the low-penetrance CHEK2 variant p.Ile157Thr (p = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45–9.55). Thus, we provide further independent evidence of CHEK2 being a moderate-penetrance TGCT predisposition gene. |
format | Online Article Text |
id | pubmed-10672725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106727252023-11-13 Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors Kirchner, Kira Seidel, Christoph Paulsen, Finn-Ole Sievers, Bianca Bokemeyer, Carsten Lessel, Davor J Clin Med Article Testicular germ cell tumors (TGCTs) represent the most frequent malignancy in young adult men and have one the highest heritability rates among all cancers. A recent multicenter case–control study identified CHEK2 as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed CHEK2 in 129 TGCT cases unselected for age of onset, histology, clinical outcome, and family history of any cancer, and the frequency of identified variants was compared to findings in 27,173 ancestry-matched cancer-free men. We identified four TGCT cases harboring a P/LP variant in CHEK2 (4/129, 3.10%), which reached statistical significance (p = 0.0191; odds ratio (OR), 4.06; 95% CI, 1.59–10.54) as compared to the control group. Cases with P/LP variants in CHEK2 developed TGCT almost 6 years earlier than individuals with CHEK2 wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between CHEK2 status and further clinical and histopathological characteristics, including histological subtypes, the occurrence of aggressive TGCT, family history of TGCT, and family history of any cancer. In addition, we found significant enrichment for the low-penetrance CHEK2 variant p.Ile157Thr (p = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45–9.55). Thus, we provide further independent evidence of CHEK2 being a moderate-penetrance TGCT predisposition gene. MDPI 2023-11-13 /pmc/articles/PMC10672725/ /pubmed/38002677 http://dx.doi.org/10.3390/jcm12227065 Text en © 2023 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 Kirchner, Kira Seidel, Christoph Paulsen, Finn-Ole Sievers, Bianca Bokemeyer, Carsten Lessel, Davor Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors |
title | Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors |
title_full | Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors |
title_fullStr | Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors |
title_full_unstemmed | Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors |
title_short | Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors |
title_sort | further association of germline chek2 loss-of-function variants with testicular germ cell tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672725/ https://www.ncbi.nlm.nih.gov/pubmed/38002677 http://dx.doi.org/10.3390/jcm12227065 |
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