Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma.
Nat Genet
; 44(3): 323-7, 2012 Feb 12.
Article
en En
| MEDLINE
| ID: mdl-22327514
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sarcoma de Ewing
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Cromosomas Humanos Par 1
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Cromosomas Humanos Par 10
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Cromosomas Humanos Par 15
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Predisposición Genética a la Enfermedad
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Proteínas de Unión al ADN
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Proteína 2 de la Respuesta de Crecimiento Precoz
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos