title: MDM2 SNP309 modifies the prognostic significance of the p53 mutational             status in patients with ovarian cancer.
abstract: A single nucleotide polymorphism (SNP309) of MDM2 causes elevated MDM2 levels             and an attenuation of p53 function. The aim of the present study was to examine             the clinical relevance of the MDM2 SNP309 in ovarian cancer.MDM2 SNP309 genotype             was analyzed in 198 patients with primary ovarian cancer. MDM2 expression was             investigated using immunohistochemistry. A functional yeast-based assay and subsequent             sequencing were performed to determine p53 mutational status. Of the patients,             44.4% (88 of 198) exhibited the common variant (T/T), 40.9% (81 of 198) the heterozygous             variant (T/G) and 14.7% (29 of 198) the homozygous variant (G/G) MDM2 SNP309 genotype.             MDM2 SNP309 was not associated with p53 mutational status, MDM2 expression, clinicopathological             parameters or prognosis. In patients with the T allele (T/T and T/G genotype),             p53 wild type carcinomas were associated with significantly improved recurrence-free             (p<0.001) and overall survival (p<0.001) as compared to p53 mutant carcinomas.             In contrast, p53 mutational status did not possess prognostic relevance in G/G             carriers. A possible functional impairment of the p53 pathway caused by the G/G             genotype of the MDM2 SNP309 may modify the association between p53 mutational             status and prognosis in ovarian cancer.
authors: Department of Gynecology and Obstetrics, Medical University Innsbruck,                     A-6020 Innsbruck, Austria.
authors: Gerda
authors: G
authors: Hofstetter
authors: Astrid
authors: A
authors: Berger
authors: Eva-Maria
authors: EM
authors: Bauer
authors: Eva
authors: E
authors: Schuster
authors: Andrea
authors: A
authors: Wolf
authors: Martina
authors: M
authors: Chamson
authors: Elisabeth
authors: E
authors: Müller-Holzner
authors: Daniel
authors: D
authors: Reimer
authors: Elena I
authors: EI
authors: Braicu
authors: Jalid
authors: J
authors: Sehouli
authors: Hanno
authors: H
authors: Ulmer
authors: Dan
authors: D
authors: Cacsire Castillo-Tong
authors: Robert
authors: R
authors: Zeillinger
authors: Nicole
authors: N
authors: Concin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2