Two functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk.
A high-frequency single-nucleotide polymorphism, SNP309 (rs2279744), in MDM2 was recently confirmed to be a modifier of cancer risk in several case-series studies: substantially earlier cancer onset was observed in SNP309 G-allele carriers than in wild-type individuals by 7-16 years.
A functional variant in the MDM2 gene promoter, single-nucleotide polymorphism 309 (SNP309) T > G (rs2279744), has been reported to cause an increase in MDM2 protein levels and impairment of p53 tumor suppressor activity, which may be associated with the development of cancer.
SNP309T>G (rs2279744) and SNP285G>C (rs117039649) in the <i>MDM2</i> promoter are thought to have opposite effects on the binding of transcription factor SP1 (specificity protein 1), and consequently on <i>MDM2</i> expression, p53 levels, cancer risk, age at onset, and prognosis.
In contrast, SNP285G>C (rs117039649), located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk.
Single nucleotide polymorphisms (SNPs) of p53 rs1042522, MDM2 rs2279744 and p21 rs1801270, all in the p53 pathway, which plays a crucial role in DNA damage and genomic instability, were reported to be associated with cancer risk and pathologic characteristics.
The MDM2 promoter region contains several polymorphisms, some of which have been associated with MDM2 expression, cancer risk and age at cancer onset. del1518 (rs3730485) is an indel polymorphism residing in the MDM2 promoter P1 and is in almost complete linkage disequilibrium with the MDM2 promoter P2 polymorphism SNP309T>G (rs2279744).