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.
- CRC, colorectal cancer
- LOH, loss of heterozygosity
- PCR, polymerase chain reaction
- SNP309, single-nucleotide polymorphism at position 309
- SSCP, single-stranded conformation polymorphism
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Funding: This work was supported by the Spanish Fondo de Investigaciones Sanitarias (grant numbers 01/1350, 01–0282 and 04–0236) and the Ministerio de Ciencia y Tecnología (grant number SAF2003/5821), Spain, grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by grants-in-aid for cancer research from the Ministry of Health, Labor and Welfare of Japan. Publication costs were supported by the Departament d’Universitats, Recerca i Societat de la Informació from the Generalitat de Catalunya.
Competing interests: None.
Published Online First 6 July 2006