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Published in: Tumor Biology 3/2015

01-03-2015 | Research Article

Impact of MDM2 gene polymorphism on sarcoma risk

Authors: Dawei Zhang, Yuanyuan Ding, Zhenlin Wang, Yan Wang, Guangyue Zhao

Published in: Tumor Biology | Issue 3/2015

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Abstract

A T>G single nucleotide polymorphism (SNP, rs2279744) of the MDM2 gene has been investigated in sarcoma community, but the findings are conflicting. This study was designed to well define the relationship between SNP rs2279744 and sarcoma risk. We did a systematic computerized search of the PubMed, Web of Science, and Science Direct databases to identify the human case–control studies investigating the relationship between SNP rs2279744 and sarcoma risk with complete genetic data. Pooled odds ratios (ORs) were calculated with the Mantel–Haenszel fixed-effect model or the DerSimonian and Laird random effects model to estimate the risk of sarcoma. Overall analysis included five independent studies. On the whole, the T/G genotype or the combined G/G and T/G genotypes appeared to be associated with approximately 1.40-fold higher risk of sarcoma relative to the T/T genotype (T/G vs. T/T: OR 1.33, 95 % CI 1.00–1.77; G/G + T/G vs. T/T: OR 1.42, 95 % CI 1.08–1.85). We noted that the Caucasian populations showed a similarly increased risk of sarcoma ascribed to the carriage of the same genotypes (T/G vs. T/T: OR 1.41, 95 % CI 1.05–1.90; G/G + T/G vs. T/T: OR 1.49, 95 % CI 1.13–1.97). This meta-analysis provides evidence that MDM2 SNP rs2279744 may be significantly associated with increased risk of sarcoma in Caucasian individuals.
Literature
2.
go back to reference Borden EC et al. Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res. 2003;9(6):1941–56.PubMed Borden EC et al. Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res. 2003;9(6):1941–56.PubMed
4.
go back to reference Grady WM, Markowitz SD. Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet. 2002;3:101–28.CrossRefPubMed Grady WM, Markowitz SD. Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet. 2002;3:101–28.CrossRefPubMed
5.
go back to reference Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003;1(14):1001–8.PubMed Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003;1(14):1001–8.PubMed
6.
go back to reference Whibley C, Pharoah PD, Hollstein M. p53 polymorphisms: cancer implications. Nat Rev Cancer. 2009;9(2):95–107.CrossRefPubMed Whibley C, Pharoah PD, Hollstein M. p53 polymorphisms: cancer implications. Nat Rev Cancer. 2009;9(2):95–107.CrossRefPubMed
7.
go back to reference Huang SF et al. Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing. Oral Oncol. 2009;45(1):16–22.CrossRefPubMed Huang SF et al. Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing. Oral Oncol. 2009;45(1):16–22.CrossRefPubMed
8.
go back to reference Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003;13(1):49–58.CrossRefPubMed Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003;13(1):49–58.CrossRefPubMed
9.
go back to reference Poyurovsky MV, Prives C. Unleashing the power of p53: lessons from mice and men. Genes Dev. 2006;20(2):125–31.CrossRefPubMed Poyurovsky MV, Prives C. Unleashing the power of p53: lessons from mice and men. Genes Dev. 2006;20(2):125–31.CrossRefPubMed
10.
go back to reference Greenblatt MS et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54(18):4855–78.PubMed Greenblatt MS et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54(18):4855–78.PubMed
11.
go back to reference Jones SN et al. Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc Natl Acad Sci U S A. 1998;95(26):15608–12.CrossRefPubMedPubMedCentral Jones SN et al. Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc Natl Acad Sci U S A. 1998;95(26):15608–12.CrossRefPubMedPubMedCentral
12.
go back to reference Freedman DA, Levine AJ. Regulation of the p53 protein by the MDM2 oncoprotein–thirty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1999;59(1):1–7.PubMed Freedman DA, Levine AJ. Regulation of the p53 protein by the MDM2 oncoprotein–thirty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1999;59(1):1–7.PubMed
13.
go back to reference Bond GL et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004;119(5):591–602.CrossRefPubMed Bond GL et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004;119(5):591–602.CrossRefPubMed
14.
go back to reference Bond GL, Hu W, Levine A. A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res. 2005;65(13):5481–4.CrossRefPubMed Bond GL, Hu W, Levine A. A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res. 2005;65(13):5481–4.CrossRefPubMed
15.
go back to reference Thurow HS et al. Ewing sarcoma: influence of TP53 Arg72Pro and MDM2 T309G SNPs. Mol Biol Rep. 2013;40(8):4929–34.CrossRefPubMed Thurow HS et al. Ewing sarcoma: influence of TP53 Arg72Pro and MDM2 T309G SNPs. Mol Biol Rep. 2013;40(8):4929–34.CrossRefPubMed
16.
go back to reference Tornesello ML et al. MDM2 and CDKN1A gene polymorphisms and risk of Kaposi’s sarcoma in African and Caucasian patients. Biomarkers. 2011;16(1):42–50.CrossRefPubMed Tornesello ML et al. MDM2 and CDKN1A gene polymorphisms and risk of Kaposi’s sarcoma in African and Caucasian patients. Biomarkers. 2011;16(1):42–50.CrossRefPubMed
17.
go back to reference Toffoli G et al. Effect of TP53 Arg72Pro and MDM2 SNP309 polymorphisms on the risk of high-grade osteosarcoma development and survival. Clin Cancer Res. 2009;15(10):3550–6.CrossRefPubMed Toffoli G et al. Effect of TP53 Arg72Pro and MDM2 SNP309 polymorphisms on the risk of high-grade osteosarcoma development and survival. Clin Cancer Res. 2009;15(10):3550–6.CrossRefPubMed
18.
go back to reference Alhopuro P et al. The MDM2 promoter polymorphism SNP309T–>G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck. J Med Genet. 2005;42(9):694–8.CrossRefPubMedPubMedCentral Alhopuro P et al. The MDM2 promoter polymorphism SNP309T–>G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck. J Med Genet. 2005;42(9):694–8.CrossRefPubMedPubMedCentral
19.
go back to reference Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.CrossRefPubMed Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.CrossRefPubMed
20.
go back to reference Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. 1999;47:15–7. Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. 1999;47:15–7.
21.
go back to reference Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med. 2006;25(20):3443–57.CrossRefPubMed Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med. 2006;25(20):3443–57.CrossRefPubMed
22.
go back to reference Leach FS et al. p53 mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 1993;53(10 Suppl):2231–4.PubMed Leach FS et al. p53 mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 1993;53(10 Suppl):2231–4.PubMed
23.
go back to reference Freedman DA, Wu L, Levine AJ. Functions of the MDM2 oncoprotein. Cell Mol Life Sci. 1999;55(1):96–107.CrossRefPubMed Freedman DA, Wu L, Levine AJ. Functions of the MDM2 oncoprotein. Cell Mol Life Sci. 1999;55(1):96–107.CrossRefPubMed
24.
go back to reference Onel K, Cordon-Cardo C. MDM2 and prognosis. Mol Cancer Res. 2004;2(1):1–8.PubMed Onel K, Cordon-Cardo C. MDM2 and prognosis. Mol Cancer Res. 2004;2(1):1–8.PubMed
25.
go back to reference Oliner JD et al. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992;358(6381):80–3.CrossRefPubMed Oliner JD et al. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992;358(6381):80–3.CrossRefPubMed
26.
go back to reference Cordon-Cardo C et al. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res. 1994;54(3):794–9.PubMed Cordon-Cardo C et al. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res. 1994;54(3):794–9.PubMed
27.
go back to reference Birgander R et al. The codon 31 polymorphism of the p53-inducible gene p21 shows distinct differences between major ethnic groups. Hum Hered. 1996;46(3):148–54.CrossRefPubMed Birgander R et al. The codon 31 polymorphism of the p53-inducible gene p21 shows distinct differences between major ethnic groups. Hum Hered. 1996;46(3):148–54.CrossRefPubMed
28.
go back to reference Arva NC et al. A chromatin-associated and transcriptionally inactive p53-Mdm2 complex occurs in mdm2 SNP309 homozygous cells. J Biol Chem. 2005;280(29):26776–87.CrossRefPubMed Arva NC et al. A chromatin-associated and transcriptionally inactive p53-Mdm2 complex occurs in mdm2 SNP309 homozygous cells. J Biol Chem. 2005;280(29):26776–87.CrossRefPubMed
29.
go back to reference Ruijs MW et al. The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li-Fraumeni syndrome and related phenotypes. Eur J Hum Genet. 2007;15(1):110–4.CrossRefPubMed Ruijs MW et al. The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li-Fraumeni syndrome and related phenotypes. Eur J Hum Genet. 2007;15(1):110–4.CrossRefPubMed
30.
go back to reference Cai X, Yang M. The functional MDM2 T309G genetic variant but not P53 Arg72Pro polymorphism is associated with risk of sarcomas: a meta-analysis. J Cancer Res Clin Oncol. 2012;138(4):555–61.CrossRefPubMed Cai X, Yang M. The functional MDM2 T309G genetic variant but not P53 Arg72Pro polymorphism is associated with risk of sarcomas: a meta-analysis. J Cancer Res Clin Oncol. 2012;138(4):555–61.CrossRefPubMed
Metadata
Title
Impact of MDM2 gene polymorphism on sarcoma risk
Authors
Dawei Zhang
Yuanyuan Ding
Zhenlin Wang
Yan Wang
Guangyue Zhao
Publication date
01-03-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2781-4

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