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Identification of 22 susceptibility loci associated with testicular germ cell tumors
Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis ide...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302763/ https://www.ncbi.nlm.nih.gov/pubmed/34301922 http://dx.doi.org/10.1038/s41467-021-24334-y |
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| author | Pluta, John Pyle, Louise C. Nead, Kevin T. Wilf, Rona Li, Mingyao Mitra, Nandita Weathers, Benita D’Andrea, Kurt Almstrup, Kristian Anson-Cartwright, Lynn Benitez, Javier Brown, Christopher D. Chanock, Stephen Chen, Chu Cortessis, Victoria K. Ferlin, Alberto Foresta, Carlo Gamulin, Marija Gietema, Jourik A. Grasso, Chiara Greene, Mark H. Grotmol, Tom Hamilton, Robert J. Haugen, Trine B. Hauser, Russ Hildebrandt, Michelle A. T. Johnson, Matthew E. Karlsson, Robert Kiemeney, Lambertus A. Lessel, Davor Lothe, Ragnhild A. Loud, Jennifer T. Loveday, Chey Martin-Gimeno, Paloma Meijer, Coby Nsengimana, Jérémie Quinn, David I. Rafnar, Thorunn Ramdas, Shweta Richiardi, Lorenzo Skotheim, Rolf I. Stefansson, Kari Turnbull, Clare Vaughn, David J. Wiklund, Fredrik Wu, Xifeng Yang, Daphne Zheng, Tongzhang Wells, Andrew D. Grant, Struan F. A. Rajpert-De Meyts, Ewa Schwartz, Stephen M. Bishop, D. Timothy McGlynn, Katherine A. Kanetsky, Peter A. Nathanson, Katherine L. |
| author_facet | Pluta, John Pyle, Louise C. Nead, Kevin T. Wilf, Rona Li, Mingyao Mitra, Nandita Weathers, Benita D’Andrea, Kurt Almstrup, Kristian Anson-Cartwright, Lynn Benitez, Javier Brown, Christopher D. Chanock, Stephen Chen, Chu Cortessis, Victoria K. Ferlin, Alberto Foresta, Carlo Gamulin, Marija Gietema, Jourik A. Grasso, Chiara Greene, Mark H. Grotmol, Tom Hamilton, Robert J. Haugen, Trine B. Hauser, Russ Hildebrandt, Michelle A. T. Johnson, Matthew E. Karlsson, Robert Kiemeney, Lambertus A. Lessel, Davor Lothe, Ragnhild A. Loud, Jennifer T. Loveday, Chey Martin-Gimeno, Paloma Meijer, Coby Nsengimana, Jérémie Quinn, David I. Rafnar, Thorunn Ramdas, Shweta Richiardi, Lorenzo Skotheim, Rolf I. Stefansson, Kari Turnbull, Clare Vaughn, David J. Wiklund, Fredrik Wu, Xifeng Yang, Daphne Zheng, Tongzhang Wells, Andrew D. Grant, Struan F. A. Rajpert-De Meyts, Ewa Schwartz, Stephen M. Bishop, D. Timothy McGlynn, Katherine A. Kanetsky, Peter A. Nathanson, Katherine L. |
| author_sort | Pluta, John |
| collection | PubMed |
| description | Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95(th) percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. |
| format | Online Article Text |
| id | pubmed-8302763 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-83027632021-08-12 Identification of 22 susceptibility loci associated with testicular germ cell tumors Pluta, John Pyle, Louise C. Nead, Kevin T. Wilf, Rona Li, Mingyao Mitra, Nandita Weathers, Benita D’Andrea, Kurt Almstrup, Kristian Anson-Cartwright, Lynn Benitez, Javier Brown, Christopher D. Chanock, Stephen Chen, Chu Cortessis, Victoria K. Ferlin, Alberto Foresta, Carlo Gamulin, Marija Gietema, Jourik A. Grasso, Chiara Greene, Mark H. Grotmol, Tom Hamilton, Robert J. Haugen, Trine B. Hauser, Russ Hildebrandt, Michelle A. T. Johnson, Matthew E. Karlsson, Robert Kiemeney, Lambertus A. Lessel, Davor Lothe, Ragnhild A. Loud, Jennifer T. Loveday, Chey Martin-Gimeno, Paloma Meijer, Coby Nsengimana, Jérémie Quinn, David I. Rafnar, Thorunn Ramdas, Shweta Richiardi, Lorenzo Skotheim, Rolf I. Stefansson, Kari Turnbull, Clare Vaughn, David J. Wiklund, Fredrik Wu, Xifeng Yang, Daphne Zheng, Tongzhang Wells, Andrew D. Grant, Struan F. A. Rajpert-De Meyts, Ewa Schwartz, Stephen M. Bishop, D. Timothy McGlynn, Katherine A. Kanetsky, Peter A. Nathanson, Katherine L. Nat Commun Article Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95(th) percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. Nature Publishing Group UK 2021-07-23 /pmc/articles/PMC8302763/ /pubmed/34301922 http://dx.doi.org/10.1038/s41467-021-24334-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Pluta, John Pyle, Louise C. Nead, Kevin T. Wilf, Rona Li, Mingyao Mitra, Nandita Weathers, Benita D’Andrea, Kurt Almstrup, Kristian Anson-Cartwright, Lynn Benitez, Javier Brown, Christopher D. Chanock, Stephen Chen, Chu Cortessis, Victoria K. Ferlin, Alberto Foresta, Carlo Gamulin, Marija Gietema, Jourik A. Grasso, Chiara Greene, Mark H. Grotmol, Tom Hamilton, Robert J. Haugen, Trine B. Hauser, Russ Hildebrandt, Michelle A. T. Johnson, Matthew E. Karlsson, Robert Kiemeney, Lambertus A. Lessel, Davor Lothe, Ragnhild A. Loud, Jennifer T. Loveday, Chey Martin-Gimeno, Paloma Meijer, Coby Nsengimana, Jérémie Quinn, David I. Rafnar, Thorunn Ramdas, Shweta Richiardi, Lorenzo Skotheim, Rolf I. Stefansson, Kari Turnbull, Clare Vaughn, David J. Wiklund, Fredrik Wu, Xifeng Yang, Daphne Zheng, Tongzhang Wells, Andrew D. Grant, Struan F. A. Rajpert-De Meyts, Ewa Schwartz, Stephen M. Bishop, D. Timothy McGlynn, Katherine A. Kanetsky, Peter A. Nathanson, Katherine L. Identification of 22 susceptibility loci associated with testicular germ cell tumors |
| title | Identification of 22 susceptibility loci associated with testicular germ cell tumors |
| title_full | Identification of 22 susceptibility loci associated with testicular germ cell tumors |
| title_fullStr | Identification of 22 susceptibility loci associated with testicular germ cell tumors |
| title_full_unstemmed | Identification of 22 susceptibility loci associated with testicular germ cell tumors |
| title_short | Identification of 22 susceptibility loci associated with testicular germ cell tumors |
| title_sort | identification of 22 susceptibility loci associated with testicular germ cell tumors |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302763/ https://www.ncbi.nlm.nih.gov/pubmed/34301922 http://dx.doi.org/10.1038/s41467-021-24334-y |
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