Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer

Abstract

We conducted a genome-wide association study for testicular germ cell tumor, genotyping 298,782 SNPs in 979 affected individuals and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three new susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5, which has previously been associated with multiple other cancers (rs4635969, OR=1.54, P=1.14x10(-23); rs2736100, OR=1.33, P=7.55x10(-15)). We also identified a locus on chromosome 12 (rs2900333, OR=1.27, P=6.16x10(-10)) that contains ATF7IP, a regulator of TERT expression. Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice.

Figure 1. Regional plots of the three new TGCT loci

The genomic regions of association with TGCT on chromosome 5p15 (a), 9p24 (b) and 12p13 (c). Shown are the −log₁₀ association P values of SNPs in 979 UK TGCT cases and 4947 UK controls. The intensity of red shading indicating the strength of LD with the index SNP. Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).