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Impact of MDM2 Single Nucleotide Polymorphism on Oral Squamous Cell Carcinoma Risk

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Abstract

Mouse Double Minute 2 (MDM2) has emerged as a pivotal cellular antagonist of p53 by destructing the suppressive function of p53 against tumorigenesis. The MDM2 309 T > G polymorphism has been studied for its association with oral squamous cell carcinoma (OSCC) susceptibility, but the evidence was confusing and inconclusive. Here, we performed a meta-analysis to estimate the effects of the 309 T > G polymorphism on the development of OSCC. The relevant studies were searched on both PubMed and Embase. We estimated the risk of OSCC using odds ratio (OR) and 95 % confidence interval (CI). In addition, between-study heterogeneity was measured by the χ 2-based statistic test; sensitivity analysis, and the funnel plots and Egger’s test were also performed in this meta-analysis. Based on five case–control studies with a total of 1,369 OSCC cases and 2,167 control subjects, the meta-analysis result showed neither increased nor decreased risk of OSCC associated with any genetic model of the 309 T > G polymorphism. Similar results were observed in the subgroup of Asians. No significant heterogeneity and publication bias were detected in the meta-analysis. The evidence provided in our study indicated that the 309 T > G polymorphism might have no significant contribution to susceptibility toward OSCC.

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References

  1. Vogelstein, B., Lane, D., & Levine, A. J. (2000). Surfing the p53 network. Nature, 408(6810), 307–310.

    Article  CAS  PubMed  Google Scholar 

  2. Hollstein, M., et al. (1991). p53 mutations in human cancers. Science, 253(5015), 49–53.

    Article  CAS  PubMed  Google Scholar 

  3. Grady, W. M., & Markowitz, S. D. (2002). Genetic and epigenetic alterations in colon cancer. Annual Review of Genomics and Human Genetics, 3, 101–128.

    Article  CAS  PubMed  Google Scholar 

  4. Moll, U. M., & Petrenko, O. (2003). The MDM2-p53 interaction. Molecular Cancer Research, 1(14), 1001–1008.

    CAS  PubMed  Google Scholar 

  5. Momand, J., et al. (1992). The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69(7), 1237–1245.

    Article  CAS  PubMed  Google Scholar 

  6. Finlay, C. A. (1993). The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Molecular and Cellular Biology, 13(1), 301–306.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Chen, J., et al. (1996). mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Molecular and Cellular Biology, 16(5), 2445–2452.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Kussie, P. H., et al. (1996). Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science, 274(5289), 948–953.

    Article  CAS  PubMed  Google Scholar 

  9. Honda, R., Tanaka, H., & Yasuda, H. (1997). Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Letters, 420(1), 25–27.

    Article  CAS  PubMed  Google Scholar 

  10. Tao, W., & Levine, A. J. (1999). Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53. Proceedings of the National Academy of Sciences of U S A, 96(6), 3077–3080.

    Article  CAS  Google Scholar 

  11. Oliner, J. D., et al. (1992). Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature, 358(6381), 80–83.

    Article  CAS  PubMed  Google Scholar 

  12. Onel, K., & Cordon-Cardo, C. (2004). MDM2 and prognosis. Molecular Cancer Research, 2(1), 1–8.

    CAS  PubMed  Google Scholar 

  13. Tachibana, M., et al. (2004). Dysfunction of p53 pathway in human colorectal cancer: analysis of p53 gene mutation and the expression of the p53-associated factors p14ARF, p33ING1, p21WAF1 and MDM2. International Journal of Oncology, 25(4), 913–920.

    CAS  PubMed  Google Scholar 

  14. Ries, S., et al. (2000). Opposing effects of Ras on p53: transcriptional activation of mdm2 and induction of p19ARF. Cell, 103(2), 321–330.

    Article  CAS  PubMed  Google Scholar 

  15. Bond, G. L., et al. (2004). A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell, 119(5), 591–602.

    Article  CAS  PubMed  Google Scholar 

  16. Gillison, M. L. (2007). Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head and Neck, 29(8), 779–792.

    Article  PubMed  Google Scholar 

  17. Misra, C., et al. (2009). Polymorphisms at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer. Molecular Carcinogenesis, 48(9), 790–800.

    Article  CAS  PubMed  Google Scholar 

  18. Chen, X., et al. (2010). Human papillomavirus seropositivity synergizes with MDM2 variants to increase the risk of oral squamous cell carcinoma. Cancer Research, 70(18), 7199–7208.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Lau, J., Ioannidis, J. P., & Schmid, C. H. (1997). Quantitative synthesis in systematic reviews. Annals of Internal Medicine, 127(9), 820–826.

    Article  CAS  PubMed  Google Scholar 

  20. Mantel, N., & Haenszel, W. (1959). Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute, 22(4), 719–748.

    CAS  PubMed  Google Scholar 

  21. DerSimonian, R., & Laird, N. (1986). Meta-analysis in clinical trials. Controlled Clinical Trials, 7(3), 177–188.

    Article  CAS  PubMed  Google Scholar 

  22. Egger, M., et al. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315(7109), 629–634.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Tu, H. F., et al. (2008). MDM2 SNP 309 and p53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation. Radiotherapy and Oncology, 87(2), 243–252.

    Article  CAS  PubMed  Google Scholar 

  24. Hamid, S., et al. (2009). MDM2 SNP309 does not confer an increased risk to oral squamous cell carcinoma but may modulate the age of disease onset. Oral Oncology, 45(6), 496–500.

    Article  CAS  PubMed  Google Scholar 

  25. Huang, S. F., et al. (2009). Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing. Oral Oncology, 45(1), 16–22.

    Article  CAS  PubMed  Google Scholar 

  26. Levine, A. J. (1997). p53, the cellular gatekeeper for growth and division. Cell, 88(3), 323–331.

    Article  CAS  PubMed  Google Scholar 

  27. Alt, J. R., et al. (2003). Mdm2 haplo-insufficiency profoundly inhibits Myc-induced lymphomagenesis. EMBO Journal, 22(6), 1442–1450.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Eymin, B., et al. (2002). Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors. Oncogene, 21(17), 2750–2761.

    Article  CAS  PubMed  Google Scholar 

  29. Sheikh, M. S., et al. (1993). The p53-binding protein MDM2 gene is differentially expressed in human breast carcinoma. Cancer Research, 53(14), 3226–3228.

    CAS  PubMed  Google Scholar 

  30. Imyanitov, E. N. (2009). Gene polymorphisms, apoptotic capacity and cancer risk. Human Genetics, 125(3), 239–246.

    Article  PubMed  Google Scholar 

  31. Post, S. M., et al. (2010). A high-frequency regulatory polymorphism in the p53 pathway accelerates tumor development. Cancer Cell, 18(3), 220–230.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Zhuo, W., et al. (2012). Association of MDM2 SNP309 variation with lung cancer risk: evidence from 7196 cases and 8456 controls. PLoS ONE, 7(7), e41546.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Chen, T., et al. (2012). Meta-analysis of associations between the MDM2-T309G polymorphism and prostate cancer risk. Asian Pacific Journal of Cancer Prevention, 13(9), 4327–4330.

    Article  PubMed  Google Scholar 

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The authors have not declared any conflicts of interest.

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Correspondence to Ping Ji.

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The authors Jian-Li Xie and Jing-Lei Yang are contributed equally to this study.

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Xie, JL., Yang, JL., Liu, DS. et al. Impact of MDM2 Single Nucleotide Polymorphism on Oral Squamous Cell Carcinoma Risk. Cell Biochem Biophys 71, 993–998 (2015). https://doi.org/10.1007/s12013-014-0298-5

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