title: p53 Arg72Pro and MDM2 309 SNPs in hereditary retinoblastoma.
abstract: The tumor suppressor p53 and its negative regulator MDM2 have crucial roles in a variety of cellular functions such as the control of the cell cycle, senescence, genome stability and apoptosis, and are frequently deregulated in carcinogenesis. Previous studies have highlighted the contribution of the common functional polymorphisms p53 p.Arg72Pro and MDM2 309SNP to the risk of both common cancers and Li-Fraumeni syndrome. Their possible role in retinoblastoma has recently been addressed by Castéra et al, who however only studied the MDM2 309SNP. Here, for the first time, we analyzed both single nucleotide polymorphisms (SNPs) in a case-control study of 111 Italian hereditary retinoblastoma patients. We found a significant association of the p53 Pro/Pro genotype with the disease (odds ratio=3.58, P=0.002). The MDM2 309SNP showed a weak negative association of allele G that deserves further investigation. These findings further support the hypothesis that genetic variability of the p53 pathway contributes to the individual susceptibility to retinoblastoma, as shown for Li-Fraumeni syndrome and a variety of non-hereditary cancers.
authors.affiliation: Medical Genetics, Department of Biotechnology, University of Siena, Siena, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Epistolato
authors.forename: Vittoria
authors.initials: V
authors.lastname: Disciglio
authors.forename: Gabriella
authors.initials: G
authors.lastname: Livide
authors.forename: Paola
authors.initials: P
authors.lastname: Berchialla
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Mencarelli
authors.forename: Annabella
authors.initials: A
authors.lastname: Marozza
authors.forename: Mariangela
authors.initials: M
authors.lastname: Amenduni
authors.forename: Theodora
authors.initials: T
authors.lastname: Hadjistilianou
authors.forename: Sonia
authors.initials: S
authors.lastname: De Francesco
authors.forename: Antonio
authors.initials: A
authors.lastname: Acquaviva
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Francesco
authors.initials: F
authors.lastname: Cetta
authors.forename: Francesca
authors.initials: F
authors.lastname: Ariani
authors.forename: Mario
authors.initials: M
authors.lastname: De Marchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Daniela
authors.initials: D
authors.lastname: Giachino
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007558:Italy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2