Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells.
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.
Alazzouzi
Hafid
H
Suriano
Gianpaolo
G
Guerra
Angel
A
Plaja
Alberto
A
Espín
Eloi
E
Armengol
Manel
M
Alhopuro
Pia
P
Velho
Sergia
S
Shinomura
Yasuhisa
Y
González-Aguilera
Juan José
JJ
Yamamoto
Hiroyuki
H
Aaltonen
Lauri A
LA
Moreno
Víctor
V
Capellà
Gabriel
G
Peinado
Miguel Angel
MA
Seruca
Raquel
R
Arango
Diego
D
Schwartz
Simó
S
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
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2