title: Meta-analysis identifies four new loci associated with testicular germ cell tumor.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute NCI, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chung
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Michelle A T
authors.initials: MA
authors.lastname: Hildebrandt
authors.forename: Roelof
authors.initials: R
authors.lastname: Koster
authors.forename: Rolf I
authors.initials: RI
authors.lastname: Skotheim
authors.forename: Christian P
authors.initials: CP
authors.lastname: Kratz
authors.forename: Clare
authors.initials: C
authors.lastname: Turnbull
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Cortessis
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bakken
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
authors.forename: R Loren
authors.initials: RL
authors.lastname: Erickson
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jacobs
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Korde
authors.forename: Sigrid M
authors.initials: SM
authors.lastname: Kraggerud
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Loud
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: Eila C
authors.initials: EC
authors.lastname: Skinner
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McGlynn
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
mesh_terms: D000465:Algorithms; D016022:Case-Control Studies; D002877:Chromosomes, Human; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000235:genetics*