Further Association of Germline <i>CHEK2</i> 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 <i>CHEK2</i> as the first moderate-penetrance TGCT predisposition gene. Here, we...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/22/7065 |
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| author | Kira Kirchner Christoph Seidel Finn-Ole Paulsen Bianca Sievers Carsten Bokemeyer Davor Lessel |
| author_facet | Kira Kirchner Christoph Seidel Finn-Ole Paulsen Bianca Sievers Carsten Bokemeyer Davor Lessel |
| author_sort | Kira Kirchner |
| collection | DOAJ |
| 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 <i>CHEK2</i> as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed <i>CHEK2</i> 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 <i>CHEK2</i> (4/129, 3.10%), which reached statistical significance (<i>p</i> = 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 <i>CHEK2</i> developed TGCT almost 6 years earlier than individuals with <i>CHEK2</i> wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between <i>CHEK2</i> 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 <i>CHEK2</i> variant p.Ile157Thr (<i>p</i> = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45–9.55). Thus, we provide further independent evidence of <i>CHEK2</i> being a moderate-penetrance TGCT predisposition gene. |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T16:43:10Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-9367857f43da43eaa15d438b20ad7f712023-11-24T14:49:20ZengMDPI AGJournal of Clinical Medicine2077-03832023-11-011222706510.3390/jcm12227065Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell TumorsKira Kirchner0Christoph Seidel1Finn-Ole Paulsen2Bianca Sievers3Carsten Bokemeyer4Davor Lessel5Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyTesticular 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 <i>CHEK2</i> as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed <i>CHEK2</i> 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 <i>CHEK2</i> (4/129, 3.10%), which reached statistical significance (<i>p</i> = 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 <i>CHEK2</i> developed TGCT almost 6 years earlier than individuals with <i>CHEK2</i> wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between <i>CHEK2</i> 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 <i>CHEK2</i> variant p.Ile157Thr (<i>p</i> = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45–9.55). Thus, we provide further independent evidence of <i>CHEK2</i> being a moderate-penetrance TGCT predisposition gene.https://www.mdpi.com/2077-0383/12/22/7065testicular germ cell tumorsgerm cell tumors<i>CHEK2</i> |
| spellingShingle | Kira Kirchner Christoph Seidel Finn-Ole Paulsen Bianca Sievers Carsten Bokemeyer Davor Lessel Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell Tumors Journal of Clinical Medicine testicular germ cell tumors germ cell tumors <i>CHEK2</i> |
| title | Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell Tumors |
| title_full | Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell Tumors |
| title_fullStr | Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell Tumors |
| title_full_unstemmed | Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell Tumors |
| title_short | Further Association of Germline <i>CHEK2</i> Loss-of-Function Variants with Testicular Germ Cell Tumors |
| title_sort | further association of germline i chek2 i loss of function variants with testicular germ cell tumors |
| topic | testicular germ cell tumors germ cell tumors <i>CHEK2</i> |
| url | https://www.mdpi.com/2077-0383/12/22/7065 |
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