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. Objectives: 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.