Identification of 22 susceptibility loci associated with testicular germ cell tumors.
![Thumbnail](/bitstream/handle/internal/4840/Identification%20of%2022%20susceptibility%20loci%20associated%20with%20testicular%20germ%20cell%20tumors.pdf.jpg?sequence=6&isAllowed=y)
View/ Open
Date
2021-07-23ICR Author
Author
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
McGlynn, KA
Kanetsky, PA
Nathanson, KL
Testicular Cancer Consortium,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Testicular Cancer Consortium
Cell Line, Tumor
Humans
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Genetic Predisposition to Disease
Chromosome Mapping
Genotype
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Male
Gene Regulatory Networks
Meta-Analysis as Topic
Genome-Wide Association Study
Protein Interaction Maps
Language
eng
Date accepted
2021-06-01
License start date
2021-07-23
Citation
Nature communications, 2021, 12 (1), pp. 4487 - ?
Publisher
NATURE PORTFOLIO