Skip to main content
Top
Published in: Medical Oncology 11/2014

Open Access 01-11-2014 | Original Paper

TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women

Authors: Agnieszka Zając, Beata Smolarz, Grzegorz Stachowiak, Jacek R. Wilczyński

Published in: Medical Oncology | Issue 11/2014

Login to get access

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.
Literature
2.
go back to reference Grosman-Dziewiszek P, Dziegiel P, Zabel M. Disturbance of gene expression in endometrial cancer as therapy aim. Ginekol Pol. 2011;82:276–80.PubMed Grosman-Dziewiszek P, Dziegiel P, Zabel M. Disturbance of gene expression in endometrial cancer as therapy aim. Ginekol Pol. 2011;82:276–80.PubMed
3.
go back to reference Hu W, Feng Z, Ma L, Wagner J, Rice JJ, Stolovitzky G, et al. A single nucleotide polymorphism in the MDM2 gene disrupts the oscillation of p53 and MDM2 levels in cells. Cancer Res. 2007;67:2757–65.PubMedCrossRef Hu W, Feng Z, Ma L, Wagner J, Rice JJ, Stolovitzky G, et al. A single nucleotide polymorphism in the MDM2 gene disrupts the oscillation of p53 and MDM2 levels in cells. Cancer Res. 2007;67:2757–65.PubMedCrossRef
4.
go back to reference Zając A, Stachowiak G, Pertyński T, Romanowicz H, Wilczyński J, Smolarz B. Association between MDM2 SNP309 polymorphism and endometrial cancer risk in Polish women. Pol J Pathol. 2012;63:278–83.PubMedCrossRef Zając A, Stachowiak G, Pertyński T, Romanowicz H, Wilczyński J, Smolarz B. Association between MDM2 SNP309 polymorphism and endometrial cancer risk in Polish women. Pol J Pathol. 2012;63:278–83.PubMedCrossRef
5.
go back to reference Dobrzycka B, Terlikowski SJ, Garbowicz M, Niklinski J, Chyczewski L, Kulikowski M. The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer. Folia Histochem Cytobiol. 2011;49:631–5.PubMedCrossRef Dobrzycka B, Terlikowski SJ, Garbowicz M, Niklinski J, Chyczewski L, Kulikowski M. The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer. Folia Histochem Cytobiol. 2011;49:631–5.PubMedCrossRef
6.
go back to reference Wang X, Yang J, Ho B, Yang Y, Huang Z, Zhang Z, et al. Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter is associated with gastric cancer susceptibility in Chinese patients. Helicobacter. 2009;13:114–9. Wang X, Yang J, Ho B, Yang Y, Huang Z, Zhang Z, et al. Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter is associated with gastric cancer susceptibility in Chinese patients. Helicobacter. 2009;13:114–9.
7.
go back to reference Pan X, Li Y, Feng J, Wang X, Hao B, Shi R, et al. A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients. BMC Cancer. 2013;18:126.CrossRef Pan X, Li Y, Feng J, Wang X, Hao B, Shi R, et al. A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients. BMC Cancer. 2013;18:126.CrossRef
8.
go back to reference Chattopadhyay P, Rathore A, Mathur M, Sarkar C, Mahapatra AK, Sinha S. Loss of heterozygosity of a locus on 17p13.3, independent of p53, is associated with higher grades of astrocytic tumors. Oncogene. 1997;15:871–4.PubMedCrossRef Chattopadhyay P, Rathore A, Mathur M, Sarkar C, Mahapatra AK, Sinha S. Loss of heterozygosity of a locus on 17p13.3, independent of p53, is associated with higher grades of astrocytic tumors. Oncogene. 1997;15:871–4.PubMedCrossRef
9.
go back to reference Chosdol K, Ahuja A, Rathore A, Misra A, Mir SH, Chattopadhyay P, et al. Study of p53 codon 72 polymorphism in various ethnic groups of North India. Curr Sci. 2002;82:1253–5. Chosdol K, Ahuja A, Rathore A, Misra A, Mir SH, Chattopadhyay P, et al. Study of p53 codon 72 polymorphism in various ethnic groups of North India. Curr Sci. 2002;82:1253–5.
10.
go back to reference Walsh CS, Miller CW, Karlan BY, Koeffler HP. Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk. Gynecol Oncol. 2007;104:660–4.PubMedCrossRef Walsh CS, Miller CW, Karlan BY, Koeffler HP. Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk. Gynecol Oncol. 2007;104:660–4.PubMedCrossRef
11.
go back to reference Terry K, McGrath M, Lee IM, Buring J, De Vivo I. MDM2 SNP309 is associated with endometrial cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:983–6.PubMedCrossRefPubMedCentral Terry K, McGrath M, Lee IM, Buring J, De Vivo I. MDM2 SNP309 is associated with endometrial cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:983–6.PubMedCrossRefPubMedCentral
12.
go back to reference Ueda M, Yamamoto M, Nunobiki O, Toji E, Sato N, Izuma S, et al. Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of gynecologic cancer. Hum Cell. 2009;22:49–54.PubMedCrossRef Ueda M, Yamamoto M, Nunobiki O, Toji E, Sato N, Izuma S, et al. Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of gynecologic cancer. Hum Cell. 2009;22:49–54.PubMedCrossRef
13.
go back to reference Kudela M, Pilka R, Lubusky M, Hejtmanek P, Dzubak P, Brychtova S. Prognostic importance of selected molecular immunohistochemical markers and DNA ploidy in endometrial cancer. Eur J Gynaecol Oncol. 2012;33:159–63.PubMed Kudela M, Pilka R, Lubusky M, Hejtmanek P, Dzubak P, Brychtova S. Prognostic importance of selected molecular immunohistochemical markers and DNA ploidy in endometrial cancer. Eur J Gynaecol Oncol. 2012;33:159–63.PubMed
14.
go back to reference Tang W, He X, Chan Y, Luo Y. Lack of association between p53 codon 72 polymorphism and endometrial cancer: a meta-analysis. Cancer Epidemiol. 2012;36:153–7.CrossRef Tang W, He X, Chan Y, Luo Y. Lack of association between p53 codon 72 polymorphism and endometrial cancer: a meta-analysis. Cancer Epidemiol. 2012;36:153–7.CrossRef
15.
go back to reference Gu Y, Zhou X, Zhang SL. Meta-analysis of an association of codon 72 polymorphisms of the p53 gene with increased endometrial cancer risk. Genet Mol Res. 2011;10:3609–19.PubMedCrossRef Gu Y, Zhou X, Zhang SL. Meta-analysis of an association of codon 72 polymorphisms of the p53 gene with increased endometrial cancer risk. Genet Mol Res. 2011;10:3609–19.PubMedCrossRef
16.
go back to reference Ashton KA, Proietto A, Otton G, Symonds I, McEvoy M, Attia J, et al. Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer. Gynecol Oncol. 2009;113:109–14.PubMedCrossRef Ashton KA, Proietto A, Otton G, Symonds I, McEvoy M, Attia J, et al. Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer. Gynecol Oncol. 2009;113:109–14.PubMedCrossRef
17.
go back to reference Nunobiki O, Ueda M, Yamamoto M, Toji E, Sato N, Izuma S, et al. Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer. Hum Cell. 2009;22:101–6.PubMedCrossRef Nunobiki O, Ueda M, Yamamoto M, Toji E, Sato N, Izuma S, et al. Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer. Hum Cell. 2009;22:101–6.PubMedCrossRef
18.
go back to reference Yoneda T, Kuboyama A, Kato K, Ohgami T, Okamoto K, Saito T, et al. Association of MDM2 SNP309 and TP53 Arg72Pro polymorphisms with risk of endometrial cancer. Oncol Rep. 2013;30:25–34.PubMedPubMedCentral Yoneda T, Kuboyama A, Kato K, Ohgami T, Okamoto K, Saito T, et al. Association of MDM2 SNP309 and TP53 Arg72Pro polymorphisms with risk of endometrial cancer. Oncol Rep. 2013;30:25–34.PubMedPubMedCentral
Metadata
Title
TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women
Authors
Agnieszka Zając
Beata Smolarz
Grzegorz Stachowiak
Jacek R. Wilczyński
Publication date
01-11-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 11/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0286-z

Other articles of this Issue 11/2014

Medical Oncology 11/2014 Go to the issue