title: Evaluation of polymorphisms in EWSR1 and risk of Ewing sarcoma: a report from the Childhood Cancer Survivor Study.
abstract: BACKGROUND
  Ewing sarcoma is a malignant bone tumor characterized by a high frequency of somatic EWSR1 translocations. Ewing sarcoma is less common in people of African or African-American ancestry, suggesting a genetic etiology.
  
  
  METHODS
  Germline DNA from white patients with Ewing sarcoma (n = 135), white controls with Wilms tumor (n = 200), and African-American controls (n = 285) was genotyped at 21 SNPs in the EWSR1 gene. Intron 7 of EWSR1, the most common site of translocation, was also sequenced in all subjects. Genetic variation between groups was evaluated statistically using exact logistic regression and Fisher exact tests.
  
  
  RESULTS
  One SNP in EWSR1 (rs2857461) showed a low level of statistical association with the diagnosis of Ewing sarcoma compared to Wilms tumor. The odds ratio for having Ewing sarcoma in people with at least one copy of the minor allele of rs2857461 was 3.57 (95% confidence interval 0.79-21.7; P = 0.07). No other SNPs or variations in intron 7 of EWSR1 were associated with Ewing sarcoma. The median relative difference in minor allele frequencies between white subjects with Ewing sarcoma and African-American controls at the evaluated EWSR1 SNPs was 45%.
  
  
  CONCLUSIONS
  Variations in EWSR1 at known SNPs or across intron 7 are not associated with the diagnosis of Ewing sarcoma. EWSR1 does not appear to be an Ewing sarcoma susceptibility gene. The genetic basis for this disease remains unknown.
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, San Francisco, California 94143-0106, USA. duboiss@peds.ucsf.edu
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.forename: Robert
authors.initials: R
authors.lastname: Goldsby
authors.forename: Mark
authors.initials: M
authors.lastname: Segal
authors.forename: Jonathan
authors.initials: J
authors.lastname: Woo
authors.forename: Kirsten
authors.initials: K
authors.lastname: Copren
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.forename: John
authors.initials: J
authors.lastname: Witte
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Louise C
authors.initials: LC
authors.lastname: Strong
mesh_terms: D000293:Adolescent; D000483:Alleles; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D020641:Polymorphism, Single Nucleotide; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000175:diagnosis / Q000235:genetics*; D009396:Wilms Tumor / Q000175:diagnosis / Q000235:genetics
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins