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

Sophie Postel-Vinay, Amélie S. Véron, Franck Tirode, Gaelle Pierron, Stéphanie Reynaud, Heinrich Kovar, Odile Oberlin, Eve Lapouble, Stelly Ballet, Carlo Lucchesi, Udo Kontny, Anna González-Neira, Piero Picci, Javier Alonso, Ana Patino-Garcia, Brigitte Bressac De Paillerets, Karine Laud, Christian Dina, Philippe Froguel, Franoise Clavel-ChapelonFrancois Doz, Jean Michon, Stephen J. Chanock, Gilles Thomas, David G. Cox, Olivier Delattre

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)323-327
Number of pages5
JournalNature Genetics
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 2012

ASJC Scopus subject areas

  • Genetics

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