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.
Subject(s)
Bone Neoplasms/genetics , Genetic Association Studies , Genetic Variation , Osteosarcoma/genetics , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Genetic Predisposition to Disease , Humans , Male , Metabolic Networks and Pathways/genetics , Middle Aged , Young AdultABSTRACT
Osteosarcoma is a primary bone malignancy that typically occurs during the pubertal growth spurt. Only a few small association studies have evaluated common germ line variation in individuals with osteosarcoma. The 8q24 chromosomal region contains several loci that are associated with risk of many different cancers. We conducted an association study of common single-nucleotide polymorphisms (SNPs) across 8q24 to explore the role this region may play in osteosarcoma risk. We genotyped 214 tag SNPs in 99 osteosarcoma cases and 1430 controls (65 controls from a hospital-based case-control study and 1365 controls from a population-based study). Additive, dominant and recessive genetic models were evaluated using unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses of nine SNPs previously associated with cancer did not show strong statistically significant associations. Of the remaining 205 SNPs, 7 were statistically significant (P
