P0104MDM2 and P53 codon 72 polymorphisms in acute myeloid leukaemia

Abstract

Background Acute myeloid leukaemia (AML) is a heterogenous disease with numerous genetic abnormalities corresponding to a variety of subtypes. P53 is a principle mediator of multiple cellular functions including cell cycle arrest, senescence, and apoptosis in response to cellular stresses. The activity of P53 may either be inactivated or attenuated in a vast majority of human cancers through mutations in the P53 gene or aberrant expression of proteins acting in the P53 tumour suppression pathway, such as its key cellular regulator MDM2. Single nucleotide polymorphism (SNP) at codon 72 of the P53 gene (A-G exchange) alters the primary structure of the P53 protein. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the promoter of the MDM2 gene which increase the expression of MDM2, thereby impairing the tumour suppressor activity of P53. We aimed at defining the role of MDM2 SNP309 and P53 codon 72 polymorphisms in the risk of AML. Methods Genotyping for MDM2 SNP309 and P53 codon 72 polymorphisms was done by AS-PCR and PCR-RFLP techniques respectively, for 50 de-novo adult AML patients and 50 healthy age and sex matched controls. Findings We found a borderline significant statistical difference between cases and controls regarding combined MDM2 T/G and P53 genotypes. There was no significant correlation between either MDM2 SNP309 or P53 codon 72 polymorphisms alone and the risk of AML. MDM2 variant genotypes were significantly associated with lower age of onset of AML and lower haemoglobin level while P53 variants were significantly associated with lower CD117 expression. Interpretation An interactive effect between MDM2 SNP309 and P53 codon 72 polymorphisms may increase the risk of AML.