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 (P_Combined = 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 (P_FBAT = 2.3 × 10⁻³). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.