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

• DOI: 10.1093/hmg/ddr207
• Publication Date: 2011-05-08T00:13:33Z
• Authors: Peter A. Kanetsky; Nandita Mitra; Saran Vardhanabhuti; David J. Vaughn; Mingyao Li; Stephanie L. Ciosek; Richard Letrero; Kurt D'Andrea; Madhavi Vaddi; David R. Doody; JoEllen Weaver; Chu Chen; Jacqueline R. Starr; Håkon Håkonarson; Daniel J. Rader; Andrew K. Godwin; Muredach P. Reilly; Stephen M. Schwartz; Katherine L. Nath...
• Keywords: Genome-wide Association Study; Genetic Association

Susceptibility to testicular germ cell tumors (TGCT) has a significant heritable component, and genome-wide association studies (GWASs) have identified with variants in several genes, including KITLG , SPRY4 BAK1 TERT DMRT1 ATF7IP . In our GWAS, we genotyped 349 TGCT cases 919 controls replicated top hits an independent set of 439 960 attempt find novel susceptibility loci. We second marker (rs7040024) the doublesex mab-3-related transcription factor 1 ( ) gene that is previously described risk allele (rs755383) at this locus. combined analysis mutually conditions on both single nucleotide polymorphism markers, had elevated odds carriage rs7040024 major A [per-allele ratio (OR) = 1.48, 95% confidence interval (CI) 1.23, 1.78; P 2.52 × 10 −5 ] compared controls, while rs755383 persisted (per OR 1.26, CI 1.08, 1.47, 0.0036). similar analyses, among men seminomatous did not differ from non-seminomatous tumors. combination strongest locus found date, greatly (OR 14.1, 5.12, 38.6; 2.98 −7 being double homozygotes for (major) alleles DMRT (rs4474514) when without TGCT. Our findings continue corroborate genes influencing male development differentiation emerged as players inherited susceptibility.