TY - JOUR
T1 - Meta-analysis identifies four new loci associated with testicular germ cell tumor
AU - Chung, Charles C.
AU - Kanetsky, Peter A.
AU - Wang, Zhaoming
AU - Hildebrandt, Michelle A.T.
AU - Koster, Roelof
AU - Skotheim, Rolf I.
AU - Kratz, Christian P.
AU - Turnbull, Clare
AU - Cortessis, Victoria K.
AU - Bakken, Anne C.
AU - Bishop, D. Timothy
AU - Cook, Michael B.
AU - Erickson, R. Loren
AU - Fosså, Sophie D.
AU - Jacobs, Kevin B.
AU - Korde, Larissa A.
AU - Kraggerud, Sigrid M.
AU - Lothe, Ragnhild A.
AU - Loud, Jennifer T.
AU - Rahman, Nazneen
AU - Skinner, Eila C.
AU - Thomas, Duncan C.
AU - Wu, Xifeng
AU - Yeager, Meredith
AU - Schumacher, Fredrick R.
AU - Greene, Mark H.
AU - Schwartz, Stephen M.
AU - McGlynn, Katherine A.
AU - Chanock, Stephen J.
AU - Nathanson, Katherine L.
N1 - Funding Information:
The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations indicate endorsement by the US Government. We thank C. Berg and P. Prorok, Division of Cancer Prevention, NCI, the screening center investigators and the staff of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, T. Riley and staff at Information Management Services, Inc., and B. O’Brien and staff at Westat, Inc., for their contributions to the PLCO Cancer Screening Trial. We thank S. Ciosek, M. McDermoth and K. D’Andrea for expert assistance in conducting TestPAC. We thank L. Kolonel and L. Le Marchand for providing access to the Multiethnic Cohort aggressive prostate cancer scan, as well as J.P. Lewinger, M. Pike, D.J. Van Den Berg and K. Siegmund for technical and scientific contributions to the parent study at USC. A portion of this work was supported by the Intramural Research Program of the NCI and by support services contract HHSN261200655004C with Westat, Inc. The Penn GWAS (UPENN) and replication effort for the TestPAC study were supported by the Abramson Cancer Center at the University of Pennsylvania and US National Institutes of Health grant R01CA114478 to P.A.K. and K.L.N. The replication effort for the ATLAS study was supported by US National Institutes of Health grant R01CA085914 to S.M.S. The analysis of the USC GWAS controls was supported by the Multiethnic Cohort Study (NCI U01-CA98758). The analyses of the USC GWAS testicular cases and the Familial Study were supported by the California Cancer Research Program (99-00505V-10260 and 03-00174VRS-30021) and by an NCI grant (R01CA102042) to V.K.C. and a Whittier Foundation award to the Norris Comprehensive Cancer Center. The study at MD Anderson was supported by the Center for Translational and Public Health Genomics of the Duncan Family Institute for Cancer Prevention and Risk Assessment and by an MD Anderson Senior Research Trust Fellowship to X.W. The UK testicular cancer study was supported by the Institute of Cancer Research, Cancer Research UK and the Wellcome Trust and made use of control data generated by the Wellcome Trust Case Control Consortium 2 (WTCCC2). Support was provided by the Norwegian Cancer Society to R.A.L. and R.I.S., by Health Region South-Eastern Norway to R.A.L. and S.D.F., and by the Norwegian ExtraFoundation for Health and Rehabilitation to S.D.F.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
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U2 - 10.1038/ng.2634
DO - 10.1038/ng.2634
M3 - Article
C2 - 23666239
AN - SCOPUS:84878735467
SN - 1061-4036
VL - 45
SP - 680
EP - 685
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -