Identification of 22 susceptibility loci associated with testicular germ cell tumors

Abstract

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 95th 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.

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Item Type:	Article
Authors/Creators:	Pluta, J Pyle, LC Nead, KT Wilf, R Li, M Mitra, N Weathers, B D’Andrea, K Almstrup, K Anson-Cartwright, L Benitez, J Brown, CD Chanock, S Chen, C Cortessis, VK Ferlin, A Foresta, C Gamulin, M Gietema, JA Grasso, C Greene, MH Grotmol, T Hamilton, RJ Haugen, TB Hauser, R Hildebrandt, MAT Johnson, ME Karlsson, R Kiemeney, LA Lessel, D Lothe, RA Loud, JT Loveday, C Martin-Gimeno, P Meijer, C Nsengimana, J Quinn, DI Rafnar, T Ramdas, S Richiardi, L Skotheim, RI Stefansson, K Turnbull, C Vaughn, DJ Wiklund, F Wu, X Yang, D Zheng, T Wells, AD Grant, SFA Rajpert-De Meyts, E Schwartz, SM Bishop, DT https://orcid.org/0000-0002-8752-8785 McGlynn, KA Kanetsky, PA Nathanson, KL the Testicular Cancer Consortium
Copyright, Publisher and Additional Information:	© The Author(s) 2021. 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/.
Dates:	Published: 23 July 2021 Published (online): 23 July 2021 Accepted: 1 June 2021
Institution:	The University of Leeds
Funding Information:	Funder Grant number Cancer Research UK c588/A19167
Depositing User:	Symplectic Publications
Date Deposited:	18 Mar 2021 15:14
Last Modified:	25 Jun 2023 22:36
Status:	Published
Publisher:	Nature Research
Identification Number:	10.1038/s41467-021-24334-y
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:172271

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Identification of 22 susceptibility loci associated with testicular germ cell tumors

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