title: Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas.
abstract: The importance of somatic TP53 mutations and germline TP53 codon 72 genotype in the survival of women with epithelial ovarian cancer is controversial. Recent data suggest that a promoter polymorphism in the MDM2 gene may influence age of cancer onset in a gender-specific fashion. We sought to determine the relationship between somatic TP53 mutations, germline genotypes at TP53 codon 72 and MDM2 SNP309, and overall survival and response to chemotherapy in a large series of patients with ovarian and peritoneal carcinomas. Of the 188 cancers, 103 (54.8%) had a TP53 mutation, of which 71% were missense mutations and 29% were null mutations. TP53 mutation status and mutation type (null vs. missense) did not influence response to therapy or overall survival. Women with the codon 72 Pro/Pro had a decreased overall survival (median, 29 months) compared with women with one or two arginine alleles (median, 49 months; P=0.04). Somatic mutation or deletion was equally common for either codon 72 allele. Age of diagnosis was not influenced by codon 72 but showed a trend for younger age in women with somatic TP53 mutations and the MDM2 G/G genotype.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Galic
authors.forename: Julia
authors.initials: J
authors.lastname: Willner
authors.forename: Melissa
authors.initials: M
authors.lastname: Wollan
authors.forename: Ruchi
authors.initials: R
authors.lastname: Garg
authors.forename: Rochelle
authors.initials: R
authors.lastname: Garcia
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Goff
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Gray
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Swisher
mesh_terms: D000483:Alleles; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2