Skip to main content
Log in

MDM2 309 T/G polymorphism is associated with colorectal cancer risk especially in Asians: a meta-analysis

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The murine double minute 2 (MDM2) gene encodes an important regulator which mainly functions as an E3 ligase. The role of the MDM2 protein in the P53 pathway has been especially well-studied. In this study, our aim was to explore the relationship between MDM2 gene 309 T/G polymorphism and colorectal cancer risk. Performing both the overall meta-analysis and the subgroup meta-analysis based on ethnicity and source of controls with a total of 7 eligible studies (2,543 cases and 2,115 controls in all), we detected a significant colorectal cancer risk variation for TG versus GG (OR = 0.73, 95% CI = 0.62–0.86) in the overall analysis and another significant colorectal cancer risk variation for TG versus GG (OR = 0.70, 95% CI = 0.59–0.83) in the population-based controls’ subgroup as well. Moreover, in the subgroup analysis based on ethnicity, significant associations were observed for all genetic models in Asians (OR = 0.51, 95% CI = 0.41–0.64 for TT versus GG; OR = 0.64, 95% CI = 0.53–0.78 for TG versus GG; OR = 0.59, 95% CI = 0.49–0.71 for dominant model; OR = 0.69, 95% CI = 0.57–0.82 for recessive model), while in Caucasians there was no obvious association. In summary, according to the results of our meta-analysis, the MDM2 309 G allele probably acts as a colorectal cancer risk factor, especially in Asians.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992;69:1237–45.

    Article  PubMed  CAS  Google Scholar 

  2. Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003;13:49–58.

    Article  PubMed  CAS  Google Scholar 

  3. 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;119:591–602.

    Article  PubMed  CAS  Google Scholar 

  4. Nunobiki O, et al. Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer. Hum Cell. 2009;22:101–6.

    Article  PubMed  Google Scholar 

  5. Economopoulos KP, Sergentanis TN. Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis. Breast Cancer Res Treat. 2010;120:211–6.

    Article  PubMed  Google Scholar 

  6. Kang S, et al. Association of p73 and MDM2 polymorphisms with the risk of epithelial ovarian cancer in Chinese women. Int J Gynecol Cancer. 2009;19:572–7.

    Article  PubMed  Google Scholar 

  7. Ueda M, et al. Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of gynecologic cancer. Hum Cell. 2009;22:49–54.

    Article  PubMed  Google Scholar 

  8. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–60.

    Article  PubMed  CAS  Google Scholar 

  9. Wilkening S, Bermejo JL, Hemminki K. MDM2 SNP309 and cancer risk: a combined analysis. Carcinogenesis. 2007;28:2262–7.

    Article  PubMed  CAS  Google Scholar 

  10. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–6.

    PubMed  CAS  Google Scholar 

  11. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    PubMed  CAS  Google Scholar 

  12. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  PubMed  CAS  Google Scholar 

  13. Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  PubMed  CAS  Google Scholar 

  14. 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;42:694–8.

    Article  PubMed  CAS  Google Scholar 

  15. Sotamaa K, et al. p53 codon 72 and MDM2 SNP309 polymorphisms and age of colorectal cancer onset in Lynch syndrome. Clin Cancer Res. 2005;11:6840–4.

    Article  PubMed  CAS  Google Scholar 

  16. Menin C, et al. Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer Inst. 2006;98:285–8.

    Article  PubMed  CAS  Google Scholar 

  17. Alazzouzi H, et al. Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells. J Med Genet. 2007;44:75–80.

    Article  PubMed  CAS  Google Scholar 

  18. Talseth BA, et al. MDM2 SNP309 T > G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patients. Int J Cancer. 2007;120:563–5.

    Article  PubMed  CAS  Google Scholar 

  19. Liu JN, et al. Genetic polymorphism in MDM2 is associated with susceptibility to colorectal cancer in a Chinese population. Zhonghua Zhong Liu Za Zhi. 2008;30:335–8.

    PubMed  CAS  Google Scholar 

  20. Chen YL, Chang YS, Chang JG, Wu SM. Genotyping of single nucleotide polymorphism in MDM2 genes by universal fluorescence primer PCR and capillary electrophoresis. Anal Bioanal Chem. 2009;394:1291–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by National 973 programs of China grants 2004CB518605 and the National 863 project of China grants 2006AA020501.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lei Yao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fang, F., Yu, XJ., Yu, L. et al. MDM2 309 T/G polymorphism is associated with colorectal cancer risk especially in Asians: a meta-analysis. Med Oncol 28, 981–985 (2011). https://doi.org/10.1007/s12032-010-9577-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9577-1

Keywords

Navigation