title: Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Our results indicate that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB.
authors.affiliation: Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Adriana Helena
authors.initials: AH
authors.lastname: de Oliveira Reis
authors.forename: Ivna Néria Silva Ribamar
authors.initials: IN
authors.lastname: de Carvalho
authors.forename: Paula Batista
authors.initials: PB
authors.lastname: de Sousa Damasceno
authors.forename: Sima Esther
authors.initials: SE
authors.lastname: Ferman
authors.forename: Evandro
authors.initials: E
authors.lastname: Lucena
authors.forename: Jorge Santiago
authors.initials: JS
authors.lastname: Lopez-Camelo
authors.forename: Héctor N
authors.initials: HN
authors.lastname: Seuánez
authors.forename: Fernando Regla
authors.initials: FR
authors.lastname: Vargas
mesh_terms: D000328:Adult; D000483:Alleles; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012175:Retinoblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2