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Novel Susceptibility Loci Identified for Ewing Sarcoma

Posted on August 09, 2018

Manhattan plot of meta-analysis –log10 P-values for the association of each SNP with EWS risk. See Machiela et al, Nature Communications 2018 Aug 9.

An international consortium of researchers reports three new common, inherited loci, and validation of three previously reported susceptibility regions that confer risk for Ewing sarcoma (EWS), a rare pediatric bone tumor for which genetic risk factors were poorly understood. The findings were published Thursday, August 8, 2018, in the journal Nature Communications.

DCEG investigators and collaborators, combined cases from the previously published EWS GWAS with four new sample sets for a total of 733 cases and 1,346 unaffected individuals. Their analyses revealed surprising risk effects from the six susceptibility loci, given the relatively small number of cases—odds ratios of 1.7, unusually high for results from a GWAS, and interactions between inherited variation and the acquired EWSR1-FLI1 translocation carried by the majority of EWS cases. Because the absolute risk for EWS is low, population-based screening with these six variants is unlikely to be effective. The researchers plan to follow up on the biologically plausible candidate genes identified through their study with the ultimate goal to expand our understanding of EWS etiology and provide insight into improved treatment and potentially preventative measures to reduce the overall burden of EWS.

Reference: Machiela, MJ., et. al. Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility. Nature Communications 2018 August 9. DOI: 10.1038/s41467-018-05537-2 [E-pub ahead of print]