Identification of 22 susceptibility loci associated with testicular germ cell tumors

John Pluta, Louise C. Pyle, Kevin T. Nead, Rona Wilf, Mingyao Li, Nandita Mitra, Benita Weathers, Kurt D’Andrea, Kristian Almstrup, Lynn Anson-Cartwright, Javier Benitez, Christopher D. Brown, Stephen Chanock, Chu Chen, Victoria K. Cortessis, Alberto Ferlin, Carlo Foresta, Marija Gamulin, Jourik A. Gietema, Chiara Grasso, Mark H. Greene, Tom Grotmol, Robert J. Hamilton, Trine B. Haugen, Russ Hauser, Michelle A. T. Hildebrandt, Matthew E. Johnson, Robert Karlsson, Lambertus A. Kiemeney, Davor Lessel, Ragnhild A. Lothe, Jennifer T. Loud, Chey Loveday, Paloma Martin-Gimeno, Coby Meijer, Jérémie Nsengimana, David I. Quinn, Thorunn Rafnar, Shweta Ramdas, Lorenzo Richiardi, Rolf I. Skotheim, Kari Stefansson, Clare Turnbull, David J. Vaughn, Fredrik Wiklund, Xifeng Wu, Daphne Yang, Tongzhang Zheng, Andrew D. Wells, Struan F. A. Grant, Ewa Rajpert- De Meyts, Stephen M. Schwartz, D. Timothy Bishop, Katherine A. McGlynn, Peter A. Kanetsky and Katherine L. Nathanson ()
Additional contact information
John Pluta: University of Pennsylvania
Louise C. Pyle: Children’s Hospital of Philadelphia
Kevin T. Nead: University of Pennsylvania
Rona Wilf: University of Pennsylvania
Mingyao Li: University of Pennsylvania
Nandita Mitra: University of Pennsylvania
Benita Weathers: University of Pennsylvania
Kurt D’Andrea: University of Pennsylvania
Kristian Almstrup: Rigshospitalet
Lynn Anson-Cartwright: University of Toronto and The Princess Margaret Cancer Centre
Javier Benitez: Spanish National Cancer Centre (CNIO)
Christopher D. Brown: University of Pennsylvania
Stephen Chanock: National Cancer Institute
Chu Chen: University of Washington
Victoria K. Cortessis: Keck School of Medicine at the University of Southern California
Alberto Ferlin: University of Brescia
Carlo Foresta: University of Padova
Marija Gamulin: University Hospital Centre Zagreb, University of Zagreb School of Medicine
Jourik A. Gietema: University Medical Center Groningen, University of Groningen
Chiara Grasso: University of Turin and CPO-Piemonte
Mark H. Greene: National Cancer Institute
Tom Grotmol: Cancer Registry of Norway
Robert J. Hamilton: University of Toronto and The Princess Margaret Cancer Centre
Trine B. Haugen: Faculty of Health Sciences, OsloMet—Oslo Metropolitan University
Russ Hauser: Harvard T.H. Chan School of Public Health
Michelle A. T. Hildebrandt: University of Texas MD Anderson Cancer Center
Matthew E. Johnson: Children’s Hospital of Philadelphia
Robert Karlsson: Karolinska Institutet
Lambertus A. Kiemeney: Radboud University Medical Center
Davor Lessel: University Medical Center Hamburg-Eppendorf
Ragnhild A. Lothe: Oslo University Hospital-Radiumhospitalet
Jennifer T. Loud: National Cancer Institute
Chey Loveday: The Institute of Cancer Research
Paloma Martin-Gimeno: Spanish National Cancer Centre (CNIO)
Coby Meijer: University Medical Center Groningen, University of Groningen
Jérémie Nsengimana: Newcastle University
David I. Quinn: Division of Oncology, Keck School of Medicine at the University of Southern California
Thorunn Rafnar: deCODE Genetics/Amgen
Shweta Ramdas: University of Pennsylvania
Lorenzo Richiardi: University of Turin and CPO-Piemonte
Rolf I. Skotheim: Oslo University Hospital-Radiumhospitalet
Kari Stefansson: deCODE Genetics/Amgen
Clare Turnbull: University of Oslo
David J. Vaughn: University of Pennsylvania
Fredrik Wiklund: Karolinska Institutet
Xifeng Wu: Zhejiang University
Daphne Yang: University of Pennsylvania
Tongzhang Zheng: Brown University
Andrew D. Wells: Children’s Hospital of Philadelphia
Struan F. A. Grant: Children’s Hospital of Philadelphia
Ewa Rajpert- De Meyts: Rigshospitalet
Stephen M. Schwartz: University of Washington
D. Timothy Bishop: University of Leeds
Katherine A. McGlynn: National Cancer Institute
Peter A. Kanetsky: H. Lee Moffitt Cancer Center and Research Institute
Katherine L. Nathanson: University of Pennsylvania

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24334-y

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