P-36: The Study of Polymorphisms of Mdm2 Gene Promoter (SNP285, SNP309, SNP344, SNP443) in Breast Cancer in North-West of Iran


Taghizadeh S *, Hosseinpour Feizi MA ,

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Objective: Murine double minute (Mdm2) oncogene which codes for the Mdm2 phosphoprotein is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes TAD of the p53 tumor suppressor and an inhibitor of p53 transcriptional activation. Recently, a T/G substitution (SNP309) in the promoter of mdm2 was identified and has been demonstrated to be associated with a significantly earlier age of onset of several tumors, including breast cancer. In the other hand, the G allele showed increased affinity for transcriptional activator Sp1, resulting in elevated Mdm2 transcription, higher mdm2 protein levels and enhanced p53 inhibition. Several polymorphisms identified in this promoter region too that include: SNP285 G/C, SNP344 T/A and SNP443 G/T. The aim is to genotype the Mdm2 promoter polymorphisms in cancer patients and controls to identify a possible association between individual genetic variation and susceptibility to breast cancer. Materials and Methods: Polymorphisms in Mdm2 promoter is analyzed using the PCR-RFLP technique and gene sequencing from PCR products that are extracted from peripheral blood samples in 112 patients and 100 normal ones. Results: Our results showed that these studied promoter polymorphisms are not any documental association with risk of breast cancer in north-west of Iran. Conclusion: As our study is the first report of these polymorphisms in breast cancer in north-west of Iran, independent studies with massive samples are needed to verify our findings. In future studies, effect of different factors such as smoking or interaction of MDM2 with other genes such as P53 and AKT, should be count