Meta-analysis identifies four new loci associated with testicular germ cell tumor

Charles C. Chung, Peter A. Kanetsky, Zhaoming Wang, Michelle A.T. Hildebrandt, Roelof Koster, Rolf I. Skotheim, Christian P. Kratz, Clare Turnbull, Victoria K. Cortessis, Anne C. Bakken, D. Timothy Bishop, Michael B. Cook, R. Loren Erickson, Sophie D. Fosså, Kevin B. Jacobs, Larissa A. Korde, Sigrid M. Kraggerud, Ragnhild A. Lothe, Jennifer T. Loud, Nazneen RahmanEila C. Skinner, Duncan C. Thomas, Xifeng Wu, Meredith Yeager, Fredrick R. Schumacher, Mark H. Greene, Stephen M. Schwartz, Katherine A. McGlynn, Stephen J. Chanock, Katherine L. Nathanson

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)680-685
Number of pages6
JournalNature genetics
Volume45
Issue number6
DOIs
StatePublished - Jun 1 2013

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ASJC Scopus subject areas

  • Genetics

Cite this

Chung, C. C., Kanetsky, P. A., Wang, Z., Hildebrandt, M. A. T., Koster, R., Skotheim, R. I., Kratz, C. P., Turnbull, C., Cortessis, V. K., Bakken, A. C., Bishop, D. T., Cook, M. B., Erickson, R. L., Fosså, S. D., Jacobs, K. B., Korde, L. A., Kraggerud, S. M., Lothe, R. A., Loud, J. T., ... Nathanson, K. L. (2013). Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nature genetics, 45(6), 680-685. https://doi.org/10.1038/ng.2634