The genetic variants predisposing to familial myeloproliferative neoplasms (MPN) are still to be defined. Germline TP53 mutations are involved in genetic predisposition to cancer. Inactivation of the p53 pathway may occur by up regulation of the MDM2 protein. A single nucleotide polymorphisms (SNP 309 T/G) in the MDM2 promoter was shown to increase the affinity of the transcriptional factor Sp1, resulting in higher levels of MDM2 RNA and protein and subsequent attenuation of the p53 pathway. We investigated the distribution of MDM2 SNP 309 in 71 familial MPN to evaluate its influence on disease susceptibility and age of disease onset, the association with the JAK2 (V617F) mutation and the impact on disease progression. The distribution of the high risk MDM2 SNP 309 (G allele) did not differ between patients with familial MPN and healthy relatives belonging to the same pedigree or to a control population. MDM2 SNP 309 did not affect age of MPN onset and was not associated with the JAK2 (V617F) mutation. Disease progression-free survival did not significantly differ between patients carrying the MDM2 SNP 309 G allele and those carrying the MDM2 SNP 309 T allele. MDM2 SNP 309 shows no clinical relevance in familial MPN.
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