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As a whole, DNA for MDM2 SNP309 analysis was available in 116 MPN patients and 84 healthy relatives. The study was approved by the Local Ethics Committee. The procedures followed were in accordance with the Declaration of Helsinki of 1975, as revised in 2000, and samples were obtained after patients provided written informed consent. We assumed heterozygosity and homozygosity for the G http://www.selleckchem.com/products/byl719.html variant of MDM2 SNP 309 as ��high risk condition�� because associated with a major inhibition of the p53 pathway, while homozygosity for the T variant was considered as ��low risk condition��. To test whether the MDM2 SNP309 G contributes to familial occurrence of MPN, two different statistical analyses were carried out. First, we analyzed the subgroup of 25 pedigrees for which both patients and healthy subjects within the same pedigree were available and we compared the distribution of the high-risk SNP309 G variant between patients and healthy relatives. Among 45 patients, 28 (62.2%) carried the high-risk G allele, whereas 40 of 84 healthy relatives (47.6%) displayed the G variant. Although the high risk G variant seemed to be more represented in patients than in healthy relatives (62.2 vs. 47.6%) the association was not statistically significant (Fisher's exact test P = 0.14). Next, the same analysis was conducted considering all familial patients from the 71 families and a control population (n = 151) consisting of subjects with normal hemogram or a hematological http://www.selleck.cn/products/gsk-j4-hcl.html reactive condition. The high-risk G variant was observed in 74 of 116 (63.8%) familial MPN patients and in 99 of 151 (65.5%) reactive conditions. The distribution of the high risk MDM2 SNP 309 did not differ between patients with familial MPN and the control population (Fisher's exact test P = 0.79). Taken together these results exclude an influence of MDM2 SNP 309 on susceptibility to familial MPN. Disease anticipation has been reported in familial MPN with a significantly younger age at diagnosis for patients in the second http://www.selleckchem.com/products/BEZ235.html generation than those in the first generation [ 3]. As the MDM2 SNP 309 G allele has been shown to impact on the age of tumor onset in patients with Li-Fraumeni syndrome carrying germline p53 mutation [11], we evaluated whether the G variant might contribute to the disease anticipation observed in familial MPN. To test this hypothesis, we considered the 36 families with two successive generations of affected individuals. The median age at diagnosis of familial MPN was significantly higher in first-generation patients (median 66 years, range 43�C85) than in second-generation patients (median 36 years; range 16�C57; P