title: A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA. mirabellol@mail.nih.gov
authors.forename: Lisa
authors.initials: L
authors.lastname: Mirabello
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdett
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Salma
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Kedest
authors.initials: K
authors.lastname: Teshome
authors.forename: Arinze
authors.initials: A
authors.lastname: Uzoka
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Tom
authors.initials: T
authors.lastname: Grotmol
authors.forename: Chester
authors.initials: C
authors.lastname: Douglass
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000235:genetics*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult