title: Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.
abstract: Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: Fredrick R
authors: FR
authors: Schumacher
authors: Zhaoming
authors: Z
authors: Wang
authors: Rolf I
authors: RI
authors: Skotheim
authors: Roelof
authors: R
authors: Koster
authors: Charles C
authors: CC
authors: Chung
authors: Michelle A T
authors: MA
authors: Hildebrandt
authors: Christian P
authors: CP
authors: Kratz
authors: Anne C
authors: AC
authors: Bakken
authors: D Timothy
authors: DT
authors: Bishop
authors: Michael B
authors: MB
authors: Cook
authors: R Loren
authors: RL
authors: Erickson
authors: Sophie D
authors: SD
authors: Fosså
authors: Mark H
authors: MH
authors: Greene
authors: Kevin B
authors: KB
authors: Jacobs
authors: Peter A
authors: PA
authors: Kanetsky
authors: Laurence N
authors: LN
authors: Kolonel
authors: Jennifer T
authors: JT
authors: Loud
authors: Larissa A
authors: LA
authors: Korde
authors: Loic
authors: L
authors: Le Marchand
authors: Juan Pablo
authors: JP
authors: Lewinger
authors: Ragnhild A
authors: RA
authors: Lothe
authors: Malcolm C
authors: MC
authors: Pike
authors: Nazneen
authors: N
authors: Rahman
authors: Mark V
authors: MV
authors: Rubertone
authors: Stephen M
authors: SM
authors: Schwartz
authors: Kimberly D
authors: KD
authors: Siegmund
authors: Eila C
authors: EC
authors: Skinner
authors: Clare
authors: C
authors: Turnbull
authors: David J
authors: DJ
authors: Van Den Berg
authors: Xifeng
authors: X
authors: Wu
authors: Meredith
authors: M
authors: Yeager
authors: Katherine L
authors: KL
authors: Nathanson
authors: Stephen J
authors: SJ
authors: Chanock
authors: Victoria K
authors: VK
authors: Cortessis
authors: Katherine A
authors: KA
authors: McGlynn
mesh_terms: D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D013736:Testicular Neoplasms / Q000235:genetics*; D014541:Uridine Kinase / Q000235:genetics*
chemical_list: C483834:UCK2 protein, human; D014541:Uridine Kinase