TP53 codon 72 polymorphism is associated with age at onset of glioblastoma

Neurology. 2009 Jan 27;72(4):332-6. doi: 10.1212/01.wnl.0000341277.74885.ec.

Abstract

Background: Functional single nucleotide polymorphisms (SNP) in codon 72 of TP53 have been shown to be a risk factor, a prognostic marker, and related factor to age at onset in various cancers.

Methods: We investigated blood samples from 254 patients with glioblastoma and 238 healthy controls.

Results: TP53 codon 72 status was not correlated with prognosis and did not differ between glioblastoma and control populations. However, the Pro/Pro genotype was overrepresented in patients <45 years (20.6% vs 6.4% in patients with glioblastoma >45 years, p = 0.002, vs 5.9% in control group, p = 0.001). We then confirmed this result on an independent series of young patients with glioblastoma. Finally, the analysis of tumor DNA found the Pro allele associated with occurrence of TP53 somatic mutation.

Conclusion: Our data suggest that TP53 functional variation is particularly critical for oncogenesis of glioblastoma in young patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Codon / blood
  • Codon / genetics*
  • Female
  • Follow-Up Studies
  • Gene Frequency / genetics
  • Genetic Variation / genetics
  • Glioblastoma / blood
  • Glioblastoma / epidemiology
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Tumor Suppressor Protein p53 / blood
  • Tumor Suppressor Protein p53 / genetics*
  • Young Adult

Substances

  • Codon
  • TP53 protein, human
  • Tumor Suppressor Protein p53