Title

Identification of 22 susceptibility loci associated with testicular germ cell tumors

Authors

John Pluta, Penn Medicine
Louise C. Pyle, The Children's Hospital of Philadelphia
Kevin T. Nead, Penn Medicine
Rona Wilf, Penn Medicine
Mingyao Li, University of Pennsylvania Perelman School of Medicine
Nandita Mitra, University of Pennsylvania Perelman School of Medicine
Benita Weathers, Penn Medicine
Kurt D’Andrea, Penn Medicine
Kristian Almstrup, Rigshospitalet
Lynn Anson-Cartwright, Ontario Cancer Institute University of Toronto
Javier Benitez, Centro Nacional de Investigaciones Oncológicas
Christopher D. Brown, University of Pennsylvania Perelman School of Medicine
Stephen Chanock, National Cancer Institute (NCI)
Chu Chen, University of Washington
Victoria K. Cortessis, Keck School of Medicine of USC
Alberto Ferlin, Università degli Studi di Brescia
Carlo Foresta, Università degli Studi di Padova
Marija Gamulin, KBC Zagreb
Jourik A. Gietema, Universitair Medisch Centrum Groningen
Chiara Grasso, Università degli Studi di Torino, Scuola di Medicina
Mark H. Greene, National Cancer Institute (NCI)
Tom Grotmol, Cancer Registry of Norway
Robert J. Hamilton, Ontario Cancer Institute University of Toronto
Trine B. Haugen, OsloMet – storbyuniversitetet
Russ Hauser, Harvard T.H. Chan School of Public Health
Michelle A.T. Hildebrandt, University of Texas MD Anderson Cancer Center
Matthew E. Johnson, The Children's Hospital of Philadelphia
Robert Karlsson, Karolinska Institutet
Lambertus A. Kiemeney, Radboud University Medical Center
Davor Lessel, Universitätsklinikum Hamburg-Eppendorf
Ragnhild A. Lothe, Rikshospitalet-Radiumhospitalet HF
Jennifer T. Loud, National Cancer Institute (NCI)

Document Type

Journal Article

Publication Date

12-1-2021

Journal

Nature Communications

Volume

12

DOI

10.1038/s41467-021-24334-y

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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