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The international TEsticular CAncer Consortium (TECAC) combined information from five GWAS (3,558 TGCT cases and 13,970 controls) to identify novel susceptibility loci. Using observed and imputed data, we conducted a fixed effects meta-analysis, including 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<5x10-8). Most loci harbor biologically plausible candidate genes. We also 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 risk, 8% of which can be attributed to the 12 new signals reported here. Our new 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 into the biological etiology of TGCT.
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- Primary Phenotype: Testicular Germ Cell Tumor
- Genetic Loci
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Principal Investigators
- Katherine Nathanson, MD. Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
- Peter Kanetsky, PhD, MPH. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
- Stephen Schwartz, PhD. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- D. Timothy Bishop, PhD. Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
- Katherine McGlynn, PhD. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
- Mark Greene, MD. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
- Fredrik Wiklund, PhD. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
- Ewa Rajpert-De Meyts, MD, DMSc. Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
- Clare Turnbull, MD, PhD, MA, MSc, MRCP. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
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Funding Sources
- U01-CA16947. National Institutes of Health, Bethesda, MD, USA.
- R01-CA114478. National Institutes of Health, Bethesda, MD, USA.
- Intramural Research program of the National Cancer Institute. National Institutes of Health, Bethesda, MD, USA.
- Abramson Cancer Center at the University of Pennsylvania. National Institutes of Health, Bethesda, MD, USA.
- Institute of Cancer Research, Cancer Research UK.
- Wellcome Trust Case Control Consortium (WTCCC).
- Movember Foundation.
- PhD Fellowship, Cancer Research UK.
- Norwegian Cancer Society Grants 418975 - 71081 - PR-2006-0387 and PK01-2007-0375.
- Nordic Cancer Union Grant S-12/07.
- Swedish Cancer Society Grant numbers 2008/708, 2010/808, 2011/484 and CAN2012/823.
- Villum Kann Rasmussen Foundation.
- NABIT Grant from the Danish Strategic Research Council.
- Novo Nordisk Foundation.
- Danish Cancer Society.
- Danish Childhood Cancer Foundation.
- Cancer Research UK Programme Award C588/a19167.
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Principal Investigators