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Meta-analysis identifies four new loci associated with testicular germ cell tumor NATURE GENETICS Chung, C. C., Kanetsky, P. A., Wang, Z., Hildebrandt, M. A., 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., Fossa, S. D., Jacobs, K. B., Korde, L. A., Kraggerud, S. M., Lothe, R. A., Loud, J. T., Rahman, N., Skinner, E. C., Thomas, D. C., Wu, X., Yeager, M., Schumacher, F. R., Greene, M. H., Schwartz, S. M., McGlynn, K. A., Chanock, S. J., Nathanson, K. L. 2013; 45 (6): 680-?

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.

View details for DOI 10.1038/ng.2634

View details for Web of Science ID 000319563900017

View details for PubMedID 23666239

View details for PubMedCentralID PMC3723930