Charles C Chung^1,2,19, Peter A Kanetsky^3,4,19, Zhaoming Wang^1,2,19, Michelle A T Hildebrandt^5,19, Roelof Koster^6,19, Rolf I Skotheim^7,8,19, Christian P Kratz^1,18,19, Clare Turnbull^9,19, Victoria K Cortessis^10,19, Anne C Bakken^7,8, D Timothy Bishop¹¹, Michael B Cook¹, R Loren Erickson¹², Sophie D Fossa¹³, Kevin B Jacobs^1,2, Larissa A Korde^1,14, Sigrid M Kraggerud^7,8, Ragnhild A Lothe^7,8, Jennifer T Loud¹, Nazneen Rahman⁹, Eila C Skinner¹⁵, Duncan C Thomas¹⁰, Xifeng Wu⁵, Meredith Yeager^1,2, Fredrick R Schumacher¹⁰, Mark H Greene¹, Stephen M Schwartz^16,17, Katherine A McGlynn¹, Stephen J Chanock^1,20 & Katherine L Nathanson^3,6,20,*

¹Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. ²Cancer Genome Research Laboratory, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, NCI-Frederick, Frederick, Maryland, USA. ³Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. ⁴Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. ⁵Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ⁶Department of Medicine, Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. ⁷Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ⁸Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway. ⁹Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK. ¹⁰Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA. ¹¹Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St. James’s University Hospital, Leeds, UK. ¹²Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. ¹³Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Oslo, Norway. ¹⁴Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington, USA. ¹⁵Department of Urology, Stanford University, Stanford, California, USA. ¹⁶Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA. ¹⁷Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA. ¹⁸Present address: Center for Pediatrics and Adolescent Medicine, Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany. ¹⁹These authors contributed equally to this work. ²⁰These authors jointly directed this work.

^*Correspondence to: Katherine L Nathanson

We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10^-8), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10^-9), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10^-12) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10^-13 and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10^-9), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.