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Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma

Sophie Postel-Vinay 1 Amélie Véron 2 Franck Tirode 3 Gaëlle Pierron 4 Stéphanie Reynaud 5 Heinrich Kovar 6 Odile Oberlin 7 Eve Lapouble 8 Stelly Ballet 4 Carlo Lucchesi 9 Udo Kontny 10 Anna González-Neira 11 Piero Picci 12 Javier Alonso 13 Ana Patiño-García 14 Brigitte Bressac de Paillerets Karine Laud 9 Christian Dina 15 Philippe Froguel 16 Françoise Clavel-Chapelon 17 Francois Doz 18 Jean Michon 19 Stephen Chanock 20 Gilles Thomas David Cox 21 Olivier Delattre 9
Abstract : Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.
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Sophie Postel-Vinay, Amélie Véron, Franck Tirode, Gaëlle Pierron, Stéphanie Reynaud, et al.. Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma. Nature Genetics, Nature Publishing Group, 2012, 44 (3), pp.323-327. ⟨10.1038/ng.1085⟩. ⟨inserm-02438686⟩

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