TY - JOUR
T1 - Identification of 22 susceptibility loci associated with testicular germ cell tumors
AU - Pluta, John
AU - Pyle, Louise C
AU - Nead, Kevin T
AU - Wilf, Rona
AU - Li, Mingyao
AU - Mitra, Nandita
AU - Weathers, Benita
AU - D'Andrea, Kurt
AU - Almstrup, Kristian
AU - Anson-Cartwright, Lynn
AU - Benitez, Javier
AU - Brown, Christopher D
AU - Chanock, Stephen
AU - Chen, Chu
AU - Cortessis, Victoria K
AU - Ferlin, Alberto
AU - Foresta, Carlo
AU - Gamulin, Marija
AU - Gietema, Jourik A
AU - Grasso, Chiara
AU - Greene, Mark H
AU - Grotmol, Tom
AU - Hamilton, Robert J
AU - Haugen, Trine B
AU - Hauser, Russ
AU - Hildebrandt, Michelle A T
AU - Johnson, Matthew E
AU - Karlsson, Robert
AU - Kiemeney, Lambertus A
AU - Lessel, Davor
AU - Lothe, Ragnhild A
AU - Loud, Jennifer T
AU - Loveday, Chey
AU - Martin-Gimeno, Paloma
AU - Meijer, Coby
AU - Nsengimana, Jérémie
AU - Quinn, David I
AU - Rafnar, Thorunn
AU - Ramdas, Shweta
AU - Richiardi, Lorenzo
AU - Skotheim, Rolf I
AU - Stefansson, Kari
AU - Turnbull, Clare
AU - Vaughn, David J
AU - Wiklund, Fredrik
AU - Wu, Xifeng
AU - Yang, Daphne
AU - Zheng, Tongzhang
AU - Wells, Andrew D
AU - Rajpert-De Meyts, Ewa
AU - Testicular Cancer Consortium
N1 - © 2021. The Author(s).
PY - 2021/7/23
Y1 - 2021/7/23
N2 - 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.
AB - 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.
KW - Cell Line, Tumor
KW - Chromosome Mapping
KW - Gene Regulatory Networks/genetics
KW - Genetic Predisposition to Disease/genetics
KW - Genome-Wide Association Study/methods
KW - Genotype
KW - Humans
KW - Linkage Disequilibrium
KW - Male
KW - Meta-Analysis as Topic
KW - Neoplasms, Germ Cell and Embryonal/genetics
KW - Polymorphism, Single Nucleotide
KW - Protein Interaction Maps/genetics
KW - Testicular Neoplasms/genetics
UR - http://www.scopus.com/inward/record.url?scp=85112280158&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-24334-y
DO - 10.1038/s41467-021-24334-y
M3 - Journal article
C2 - 34301922
SN - 2041-1722
VL - 12
SP - 4487
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4487
ER -