title: Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells.
abstract: BACKGROUND
  Mdm2 is a natural inhibitor of p53 function and its overexpression impairs p53 transcriptional activity. T-->G single-nucleotide polymorphism at position 309 (SNP309) of mdm2 induces overexpression of mdm2, but inhibits p53.
  
  
  OBJECTIVE
  To determine whether SNP309 is a risk-modifier polymorphism in colorectal cancer (CRC) and whether tumour selection of P53 mutations are influenced by SNP309.
  
  
  METHODS
  Single-stranded conformation polymorphism and automatic sequencing were performed.
  
  
  RESULTS
  SNP309 is not associated with the risk of CRC or recurrence of tumours. These data do not over-ride the tumour-selection capabilities of P53 mutations in CRC. However, a significant association with non-dominant-negative P53 mutations (p = 0.02) was found.
  
  
  CONCLUSIONS
  MDM2-SNP309 favours tumour selection of non-dominant negative P53 mutations in CRC, which also show an earlier age of tumour onset.
authors.forename: Hafid
authors.initials: H
authors.lastname: Alazzouzi
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
authors.forename: Angel
authors.initials: A
authors.lastname: Guerra
authors.forename: Alberto
authors.initials: A
authors.lastname: Plaja
authors.forename: Eloi
authors.initials: E
authors.lastname: Espín
authors.forename: Manel
authors.initials: M
authors.lastname: Armengol
authors.forename: Pia
authors.initials: P
authors.lastname: Alhopuro
authors.forename: Sergia
authors.initials: S
authors.lastname: Velho
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Juan José
authors.initials: JJ
authors.lastname: González-Aguilera
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Peinado
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Diego
authors.initials: D
authors.lastname: Arango
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2