1. Identification of 22 susceptibility loci associated with testicular germ cell tumors
- Author
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Mingyao Li, Chey Loveday, Tongzhang Zheng, Chu Chen, Paloma Martin-Gimeno, Mark H. Greene, Javier Benitez, Stephen J. Chanock, Coby Meijer, Daphne Yang, Christopher D. Brown, Thorunn Rafnar, Lorenzo Richiardi, Marija Gamulin, Kari Stefansson, Michelle A.T. Hildebrandt, Matthew E. Johnson, Shweta Ramdas, Jourik A. Gietema, David J. Vaughn, Kevin T. Nead, Robert Karlsson, Struan F.A. Grant, Peter A. Kanetsky, Kristian Almstrup, David I. Quinn, Katherine L. Nathanson, Kurt D'Andrea, D. Timothy Bishop, Andrew D. Wells, Nandita Mitra, Katherine A. McGlynn, Jennifer T. Loud, Carlo Foresta, Lynn Anson-Cartwright, Jérémie Nsengimana, Alberto Ferlin, Lambertus A. Kiemeney, Rolf Inge Skotheim, Victoria K. Cortessis, Xifeng Wu, Chiara Grasso, Ragnhild A. Lothe, Tom Grotmol, Russ Hauser, Trine B. Haugen, Fredrik Wiklund, Clare Turnbull, Benita Weathers, Louise C. Pyle, Robert J. Hamilton, Stephen M. Schwartz, Davor Lessel, John Pluta, Ewa Rajpert-De Meyts, Rona Wilf, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
- Subjects
Oncology ,Male ,Linkage disequilibrium ,Somatic cell ,General Physics and Astronomy ,Genome-wide association study ,Disease ,VARIANTS ,DMRT1 ,Linkage Disequilibrium ,Neoplasms, Germ Cell and Embryonal / metabolism ,Cell Line, Tumor ,Chromosome Mapping ,Gene Regulatory Networks ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Meta-Analysis as Topic ,Neoplasms, Germ Cell and Embryonal ,Protein Interaction Maps ,Testicular Neoplasms ,Polymorphism, Single Nucleotide ,Testicular Neoplasms / genetics ,0302 clinical medicine ,Gene Regulatory Networks / genetics ,Neoplasms ,Medicine ,FAMILIAL RISK ,Cancer genetics ,Genome-Wide Association Study / methods ,0303 health sciences ,Tumor ,Multidisciplinary ,testicular germ cell tumors (TGCT) ,Protein Interaction Maps / genetics ,Single Nucleotide ,CANCER ,medicine.anatomical_structure ,SINGLE ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,030220 oncology & carcinogenesis ,CENP-I ,Germ cell ,endocrine system ,medicine.medical_specialty ,Science ,GENOTYPE IMPUTATION ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Testicular cancer ,Internal medicine ,Neoplasms, Germ Cell and Embryonal / genetics ,Polymorphism ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,030304 developmental biology ,Genetic association study ,business.industry ,Cancer ,General Chemistry ,medicine.disease ,Genetic Predisposition to Disease / genetics ,BAX ,Germ Cell and Embryonal ,Testicular Neoplasms / metabolism ,business - 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., Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.
- Published
- 2020