title: Germ-line genetic variation of TP53 in osteosarcoma.
abstract: BACKGROUND
  Osteosarcoma (OS) has been well described in individuals with germ-line TP53 mutations (Li-Fraumeni Syndrome) but typically occurs sporadically in adolescents and young adults. Single nucleotide polymorphisms (SNPs), the most common germ-line genetic variation, have been associated with risk for other types of cancer. We hypothesized that genetic variation in TP53 could be associated with OS risk based on its critical role in cell growth and effect of somatic mutations in OS tumors.
  
  
  METHODS
  Twelve common SNPs in TP53 were genotyped in a case-control study of sporadic OS. These SNPs spanned the TP53 locus and captured common haplotypes. Genotype data were analyzed using contingency tables for additive, dominant, and recessive genetic models. PHASEv2.1 and HaploStats were used to evaluate haplotypes.
  
  
  RESULTS
  The recessive model suggested an increased risk of OS when two copies of TP53-34 C>G variant (IVS2+38, rs1642785) were present, P = 0.041, odds ratio (OR) 6.70 (95% confidence interval [CI] 1.06-41.6). The TP53-01 variant C>G (Pro72Arg, rs1042522) may also be associated with increased risk for OS, P = 0.028, OR 7.5 (95% CI 1.20-46.3). Common TP53 haplotypes as well as the remaining 10 SNPs were not associated with risk for OS.
  
  
  CONCLUSIONS
  These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2+38 and Pro72Arg. The findings warrant replication in further studies.
authors.affiliation: Pediatric Oncology Branch, CCR, NCI, NIH, Bethesda, Maryland. savagesh@mail.nih.gov
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
authors.forename: Laura
authors.initials: L
authors.lastname: Burdett
authors.forename: Rebecca
authors.initials: R
authors.lastname: Troisi
authors.forename: Chester
authors.initials: C
authors.lastname: Douglass
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53