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Nat Genet. 2017 Jul;49(7):1141-1147. doi: 10.1038/ng.3879. Epub 2017 Jun 12.

Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
2
Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
3
Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
4
Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark.
5
Cancer Registry of Norway, Oslo, Norway.
6
Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
7
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
8
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
9
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
10
Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
11
Division of Human Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
12
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
13
Institute for Systems Biology, Seattle, Washington, USA.
14
Department of Biostatistics, Harvard School of Public Health, Harvard University, Boston, Massachusetts, USA.
15
Genomics England, London, UK.
16
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
17
Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract

The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10-8). Most loci harbor biologically plausible candidate genes. We refined previously reported associations at 9p24.3 and 19p12 by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT susceptibility alleles, move the field closer to a comprehensive understanding of the underlying genetic architecture of TGCT, and provide further clues to the etiology of TGCT.

PMID:
28604732
PMCID:
PMC5490654
DOI:
10.1038/ng.3879
[Indexed for MEDLINE]
Free PMC Article

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