Title

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

Authors

Zhaoming Wang, National Cancer Institute (NCI)
Katherine A. McGlynn, National Cancer Institute (NCI)
Ewa Rajpert-De Meyts, Rigshospitalet
D. Timothy Bishop, University of Leeds, School of Medicine
Charles C. Chung, National Cancer Institute (NCI)
Marlene D. Dalgaard, Rigshospitalet
Mark H. Greene, National Cancer Institute (NCI)
Ramneek Gupta, Technical University of Denmark
Tom Grotmol, Cancer Registry of Norway
Trine B. Haugen, OsloMet – storbyuniversitetet
Robert Karlsson, Karolinska Institutet
Kevin Litchfield, The Institute of Cancer Research
Nandita Mitra, University of Pennsylvania
Kasper Nielsen, Technical University of Denmark
Louise C. Pyle, University of Pennsylvania Perelman School of Medicine
Stephen M. Schwartz, Fred Hutchinson Cancer Research Center
Vésteinn Thorsson, Institute for Systems Biology
Saran Vardhanabhuti, Harvard T.H. Chan School of Public Health
Fredrik Wiklund, Karolinska Institutet
Clare Turnbull, The Institute of Cancer Research
Stephen J. Chanock, National Cancer Institute (NCI)
Peter A. Kanetsky, Moffitt Cancer Center
Katherine L. Nathanson, University of Pennsylvania Perelman School of Medicine
Alberto Ferlin, Università degli Studi di Padova
Jourik A. Gietema, Universitair Medisch Centrum Groningen
Victoria Cortessis, Keck School of Medicine of USC
Russ Hauser, Harvard T.H. Chan School of Public Health
Michelle Hildebrandt, University of Texas MD Anderson Cancer Center
Lambertus A. Kiemeney, Radboud University Medical Center
Christian Kubisch, Universitätsklinikum Hamburg-Eppendorf
Davor Lessel, Universitätsklinikum Hamburg-Eppendorf
Thorunn Rafnar, deCODE genetics

Document Type

Journal Article

Publication Date

7-1-2017

Journal

Nature Genetics

Volume

49

DOI

10.1038/ng.3879

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- A nalysis, 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.

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