Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma

Pediatr Blood Cancer. 2012 Jul 15;59(1):39-43. doi: 10.1002/pbc.24014. Epub 2011 Dec 16.

Abstract

Background: Retinoblastoma (RB) accounts for 3% of all childhood malignancies, with different incidences around the world. This malignancy results from loss-of-function of both RB1 alleles although other genes, like MDM2 and MDM4, have been proposed to be involved in tumor development.

Procedure: We genotyped rs2279744T>G and rs937283A>G in MDM2, and rs4252668T>C and rs116197192G>A in MDM4, in 104 unrelated RB patients and 104 controls. Sixty-month survival Kaplan-Meier curves and χ(2)-tests were performed for estimating the putative effect of MDM2 and MDM4 alleles on disease progression and survival of RB patients.

Results: MDM2 rs2279744G was significantly more frequent in controls, indicating an apparently protective effect on RB development. However, survival of patients who carried a constitutional RB1 mutation was significantly lower with rs2279744TG or GG than with rs2279744TT. Presence of rs2279744G and a constitutional RB1 mutation was sixfold more frequent in the 0-12 month age group than other age groups at onset of symptoms (P = 0.0401). MDM4 rs4252668C was present at a significantly higher frequency in controls while the frequency of MDM4 rs116197192G was significantly higher in RB patients, suggesting that this allele might increase the risk of developing RB.

Conclusion: Our results indicate that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles*
  • Cell Cycle Proteins
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Genotyping Techniques
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation, Missense*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Polymorphism, Genetic*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Retinoblastoma / genetics*
  • Retinoblastoma / metabolism
  • Retinoblastoma / mortality*
  • Retrospective Studies
  • Survival Rate

Substances

  • Cell Cycle Proteins
  • MDM4 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2