BoneKEy Reports | BoneKEy Watch
Genetic predisposition to osteosarcoma
DOI:10.1038/bonekey.2013.185
The genes associated with susceptibility to osteosarcoma, the most common type of bone cancer in young people, are not well characterized. Savage et al. report on their genome-wide association study performed on DNA from 941 people diagnosed with osteosarcoma, compared with DNA from 3291 controls–adults aged over 55 years and of European ancestry who did not have any form of cancer.
Analysis revealed two separate loci that achieved genome-wide significance. The first was rs1906953 within the GRM4 gene, which codes for glutamate receptor metabotropic 4 (P=8.1 × 10−9). This locus, on chromosome 6 at 6p21.3, was positively associated with susceptibility to osteosarcoma with an odds ratio (OR) of 1.57 (95% confidence interval=1.35–1.83). The other was at rs7591996 and rs10208273, which are within a region of DNA lying in between any known genes on chromosome 2, at 2p25.2.
A third locus was rs17206779 within the ADAMTS6 gene, which codes for ADAM metallopeptidase with thrombospondin type 1 motif 6 on chromosome 5 at 5q12.3. This locus was highlighted but did not reach genome-wide significance.
Editor’s comment: The ORs reported within this study are greater than 1.5 and higher than those previously seen for most genetic variants with an association with the risk of cancer in adults. They are on a par with those reported for genes related to susceptibility to other pediatric cancers such as acute lymphoblastic leukemia and Ewing sarcoma. The two loci therefore warrant further investigation.
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