Identification of 22 susceptibility loci associated with testicular germ cell tumors
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Published:2021-07-23
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Pluta John, Pyle Louise C.ORCID, Nead Kevin T.ORCID, Wilf Rona, Li MingyaoORCID, Mitra Nandita, Weathers Benita, D’Andrea Kurt, Almstrup KristianORCID, Anson-Cartwright LynnORCID, Benitez Javier, Brown Christopher D., Chanock StephenORCID, Chen Chu, Cortessis Victoria K., Ferlin AlbertoORCID, Foresta CarloORCID, Gamulin MarijaORCID, Gietema Jourik A., Grasso ChiaraORCID, Greene Mark H.ORCID, Grotmol TomORCID, Hamilton Robert J., Haugen Trine B.ORCID, Hauser Russ, Hildebrandt Michelle A. T., Johnson Matthew E., Karlsson RobertORCID, Kiemeney Lambertus A.ORCID, Lessel DavorORCID, Lothe Ragnhild A.ORCID, Loud Jennifer T., Loveday CheyORCID, Martin-Gimeno Paloma, Meijer Coby, Nsengimana JérémieORCID, Quinn David I., Rafnar ThorunnORCID, Ramdas Shweta, Richiardi LorenzoORCID, Skotheim Rolf I.ORCID, Stefansson Kari, Turnbull ClareORCID, Vaughn David J., Wiklund FredrikORCID, Wu XifengORCID, Yang Daphne, Zheng Tongzhang, Wells Andrew D., Grant Struan F. A.ORCID, Rajpert-De Meyts EwaORCID, Schwartz Stephen M.ORCID, Bishop D. TimothyORCID, McGlynn Katherine A., Kanetsky Peter A.ORCID, Nathanson Katherine L.ORCID, Kubisch Christian,
Abstract
AbstractTesticular 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference93 articles.
1. Gurney, J. K. et al. International trends in the incidence of testicular cancer: lessons from 35 years and 41 countries. Eur. Urol. 76, 615–623 (2019). 2. Howlader, N. et al. SEER Cancer Statistics Review, 1975–2017 (National Cancer Institute, 2020). 3. Fossa, S. D. et al. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J. Natl Cancer Inst. 97, 1056–1066 (2005). 4. Dieckmann, K. P. & Pichlmeier, U. Clinical epidemiology of testicular germ cell tumors. World J. Urol. 22, 2–14 (2004). 5. Cheng, L. et al. Testicular cancer. Nat. Rev. Dis. Prim. 4, 29 (2018).
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