MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

A single nucleotide polymorphism (SNP309) of MDM2 causes elevated MDM2 levelsand an attenuation of p53 function. The aim of the present study was to examinethe clinical relevance of the MDM2 SNP309 in ovarian cancer.MDM2 SNP309 genotypewas analyzed in 198 patients with primary ovarian cancer. MDM2 expression wasinvestigated using immunohistochemistry. A functional yeast-based assay and subsequentsequencing 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 heterozygousvariant (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, clinicopathologicalparameters 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/Gcarriers. A possible functional impairment of the p53 pathway caused by the G/Ggenotype of the MDM2 SNP309 may modify the association between p53 mutationalstatus and prognosis in ovarian cancer.