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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

Authors: Lisa Mirabello, Kai Yu, Sonja I Berndt, Laurie Burdett, Zhaoming Wang, Salma Chowdhury, Kedest Teshome, Arinze Uzoka, Amy Hutchinson, Tom Grotmol, Chester Douglass, Richard B Hayes, Robert N Hoover, Sharon A Savage, the National Osteosarcoma Etiology Study Group

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.
Appendix
Available only for authorised users
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Metadata
Title
A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma
Authors
Lisa Mirabello
Kai Yu
Sonja I Berndt
Laurie Burdett
Zhaoming Wang
Salma Chowdhury
Kedest Teshome
Arinze Uzoka
Amy Hutchinson
Tom Grotmol
Chester Douglass
Richard B Hayes
Robert N Hoover
Sharon A Savage
the National Osteosarcoma Etiology Study Group
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-209

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