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

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

Published In Nat Genet, (2013 Jun)

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.

PubMed ID: 23666239

MeSH Terms: Algorithms; Case-Control Studies; Chromosomes, Human; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Male; Models, Genetic; Neoplasms, Germ Cell and Embryonal/genetics*; Polymorphism, Single Nucleotide; Risk Factors; Testicular Neoplasms/genetics*