%0 Journal Article
%T A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma
%A Lisa Mirabello
%A Kai Yu
%A Sonja I Berndt
%A Laurie Burdett
%A Zhaoming Wang
%A Salma Chowdhury
%A Kedest Teshome
%A Arinze Uzoka
%A Amy Hutchinson
%A Tom Grotmol
%A Chester Douglass
%A Richard B Hayes
%A Robert N Hoover
%A Sharon A Savage
%A the National Osteosarcoma Etiology Study Group
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-209
%X 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.Osteosarcoma (OS) is the most common primary malignant bone tumor and typically occurs in adolescents and young adults (Damron et al, 2007; Mascarenhas L, 2006; Stiller CA, 2006). OS incidence has a bimodal age distribution; the primary peak occurs during adolescence and a second, much smaller peak is present in the elderly [1,2]. In young patients, OS incidence correlates with puberty and bone growth. The peak incidence of both OS and puberty tend to occur earlier in females. OS incidence is higher in males, who usually grow taller than females, and it typically occurs at sites of rapid bone growth (e.g., the metaphyses of long bones) [1]. The incidence peak in adolescence is followed by a rapid decline and a plateau when bone growth is complete (after age 24 years) [3]. Several studies have suggested that being taller than average at diagnosis is associated with increased OS risk [4-11]. A recent meta-analysis of height at diagnosis and birth-weight as OS risk factors found that high birth-weight (OR 1.35, 95% CI 1.01-1.79, compared to average birth-weight subjects) and being taller than average were significant OS risk factors (for those ¡Ý90th percentile of height: OR 2.63, 95% CI 1.98-3.49, compared to those ¡Ü50th
%U http://www.biomedcentral.com/1471-2407/11/209