title: TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women.
abstract: The aim of the study was to determine an association of TP53 codon 72 (Arg72Pro, G>C transversion, rs1042522) and MDM2 SNP309 (T>G change, rs2279744) polymorphisms in endometrial cancer (EC) of postmenopausal women, regarding grading and staging of EC. In the study, endometrial samples from 202 postmenopausal female patients (the study group, n = 152, was women with EC; the control group, n = 50, cancer-free patients) were taken for the evaluation of two gene polymorphisms: TP53 codon 72 and MDM2 SNP309, respectively. Genotypic analyses were performed using the PCR-RFLP technique. There were significant differences in the frequency of TP53 and MDM2 genotypes in EC patients-increased EC occurrence was observed with the presence of MDM2 G/G and TP53 Arg/Arg genotypes, while allele Pro of TP53 decreased cancer risk. Analysis of combined MDM2/TP53 polymorphisms revealed that T/T-Pro/Arg genotype decreased EC risk, whereas G/G-Arg/Arg genotype increased it. Association of these genetic polymorphisms with histological grading showed increased MDM2 G/G homozygote and TP53 Arg/Arg homozygote frequencies in grading 2 as well as allele G overrepresentation in G1 and G3 EC patients. Finally, with clinical FIGO staging under evaluation, an increase in MDM2 G/G and TP53 Arg/Arg homozygote frequencies in staging I and TP53 Arg/Arg homozygote frequencies in staging II were observed. Co-occurrence of some MDM2 SNP309 and TP53 codon 72 polymorphisms seems to influence EC risk, involving grading and staging of this neoplasm at the same time.
authors.affiliation: Department of Gynecology and Gynecologic Oncology, Polish Mother's Memorial Hospital, Research Institute, 281/289 Rzgowska St., 93-338, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zając
authors.forename: Beata
authors.initials: B
authors.lastname: Smolarz
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Stachowiak
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wilczyński
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2