Open Access Open Badges Research article

A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

Lisa Mirabello1*, Kai Yu1, Sonja I Berndt1, Laurie Burdett2, Zhaoming Wang2, Salma Chowdhury2, Kedest Teshome2, Arinze Uzoka2, Amy Hutchinson2, Tom Grotmol3, Chester Douglass4, Richard B Hayes5, Robert N Hoover1, Sharon A Savage1 and the National Osteosarcoma Etiology Study Group

Author Affiliations

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA

2 Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Inc., Gaithersburg, MD, USA

3 Cancer Registry of Norway, PO Box 5313 Majorstuen, NO-0304 Oslo, Norway

4 Harvard School of Dental Medicine, Boston, MA, USA

5 Division of Epidemiology, Department of Environmental Medicine, New York University, New York, NY, USA

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BMC Cancer 2011, 11:209  doi:10.1186/1471-2407-11-209

Published: 29 May 2011



Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.


We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).


Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: MDM2, MPG, FGF2, FGFR3, GNRH2, and IGF1.


Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.