Conflict of interest: Nothing to report.
Evaluation of polymorphisms in EWSR1 and risk of Ewing sarcoma: A report from the childhood cancer survivor study†
Version of Record online: 25 JUL 2011
Copyright © 2011 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 59, Issue 1, pages 52–56, 15 July 2012
How to Cite
DuBois, S. G., Goldsby, R., Segal, M., Woo, J., Copren, K., Kane, J. P., Pullinger, C. R., Matthay, K. K., Witte, J., Lessnick, S. L., Robison, L. L., Bhatia, S. and Strong, L. C. (2012), Evaluation of polymorphisms in EWSR1 and risk of Ewing sarcoma: A report from the childhood cancer survivor study. Pediatr. Blood Cancer, 59: 52–56. doi: 10.1002/pbc.23263
- Issue online: 17 MAY 2012
- Version of Record online: 25 JUL 2011
- Manuscript Accepted: 9 JUN 2011
- Manuscript Received: 9 MAY 2011
- NIH/NCRR. Grant Number: UCSF-CTSI UL1 RR024131
- Campini Foundation. Grant Number: U24 CA055727
- Ewing sarcoma;
- genetic epidemiology;
- single nucleotide polymorphism
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.
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.
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%.
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. Pediatr Blood Cancer 2012; 59: 52–56. © 2011 Wiley Periodicals, Inc.