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A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility


, : A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. Human Molecular Genetics 20(15): 3109-3117

Susceptibility to testicular germ cell tumors (TGCT) has a significant heritable component, and genome-wide association studies (GWASs) have identified association with variants in several genes, including KITLG, SPRY4, BAK1, TERT, DMRT1 and ATF7IP. In our GWAS, we genotyped 349 TGCT cases and 919 controls and replicated top hits in an independent set of 439 cases and 96 controls in an attempt to find novel TGCT susceptibility loci. We identified a second marker (rs7424) in the doublesex and mab-3-related transcription factor 1 (DMRT1) gene that is independent of the previously described risk allele (rs755383) at this locus. In combined analysis that mutually conditions on both DMRT1 single nucleotide polymorphism markers, TGCT cases had elevated odds of carriage of the rs7424 major A allele [per-allele odds ratio (OR) = 1.48, 95% confidence interval (CI) 1.23, 1.78; P = 2.52 1–7) of being double homozygotes for the risk (major) alleles at DMRT (rs7424) and KITLG (rs4474514) when compared with men without TGCT. Our findings continue to corroborate that genes influencing male germ cell development and differentiation have emerged as the major players in inherited TGCT susceptibility.

US$19.90

PMID: 21551455

DOI: 10.1093/hmg/ddr207


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