Meta-analysis of Associations between the MDM2-T309G Polymorphism and Prostate Cancer Risk

  • Chen, Tao (State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, School of Medicine, Shenzhen University) ;
  • Yi, Shang-Hui (Teaching and Research Section of Epidemiology, Hunan Normal University) ;
  • Liu, Xiao-Yu (State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, School of Medicine, Shenzhen University) ;
  • Liu, Zhi-Gang (State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, School of Medicine, Shenzhen University)
  • Published : 2012.09.30


The mouse double minute 2 (MDM2) gene plays a key role in the p53 pathway, and the SNP 309T/G single-nucleotide polymorphism in the promoter region of MDM2 has been shown to be associated with increased risk of cancer. However, no consistent results were found concerning the relationships between the polymorphism and prostate cancer risk. This meta-analysis, covering 4 independent case-control studies, was conducted to better understand the association between MDM2-SNP T309G and prostate cancer risk focusing on overall and subgroup aspects. The analysis revealed, no matter what kind of genetic model was used, no significant association between MDM2-SNP T309G and prostate cancer risk in overall analysis (GT/TT: OR = 0.84, 95%CI = 0.60-1.19; GG/TT: OR = 0.69, 95%CI = 0.43-1.11; dominant model: OR = 0.81, 95%CI= 0.58-1.13; recessive model: OR = 1.23, 95%CI = 0.95-1.59). In subgroup analysis, the polymorphism seemed more likely to be a protective factor in Europeans (GG/TT: OR = 0.52, 95%CI = 0.31-0.87; recessive model: OR = 0.58, 95%CI = 0.36-0.95) than in Asian populations, and a protective effect of the polymorphism was also seen in hospital-based studies in all models (GT/TT: OR = 0.74, 95%CI = 0.57-0.97; GG/TT: OR = 0.55, 95%CI = 0.38-0.79; dominant model: OR = 0.69, 95%CI = 0.54-0.89; recessive model: OR = 0.70, 95%CI = 0.51-0.97). However, more primary studies with a larger number of samples are required to confirm our findings.


  1. Boersma BJ, Howe TM, Goodman JE, et al (2006). Association of breast cancer outcome with status of p53 and MDM2 SNP309. J Natl Cancer Inst, 98, 911-9.
  2. Bond GL, Hu W, Bond EE, 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, 591-602.
  3. Bond GL, Hu W, Levine A (2005). A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res, 65, 5481-4.
  4. Bouska A & Eischen CM (2009). Mdm2 affects genome stability independent of p53. Cancer Res, 69, 1697-701.
  5. Detchokul S & Frauman AG (2011). Recent developments in prostate cancer biomarker research: therapeutic implications. Br J Clin Pharmacol, 71, 157-74.
  6. Eischen CM & Lozano G (2009). p53 and MDM2: antagonists or partners in crime? Cancer Cell, 15, 161-2.
  7. Jaboin JJ, Hwang M, Perez CA, et al (2011). No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes. Urol Oncol, 29, 319-23.
  8. Kibel AS, Jin CH, Klim A, et al (2008). Association between polymorphisms in cell cycle genes and advanced prostate carcinoma. Prostate, 68, 1179-86.
  9. Kruse JP & Gu W (2009) . Modes of p53 regulation. Cell, 137, 609-22.
  10. Liu J, Zheng Y, Lei D, et al (2011). MDM2 309T>G polymorphism and risk of squamous cell carcinomas of head and neck: a meta-analysis. Asian Pac J Cancer Prev, 12, 1899-903.
  11. Ma H, Hu Z, Zhai X, et al (2006). Polymorphisms in the MDM2 promoter and risk of breast cancer: a case-control analysis in a Chinese population. Cancer Lett, 240, 261-7.
  12. Ma HB, Huang T, Han F, et al (2012). Association Between MDM2 Promoter SNP309 T/G Polymorphism and Liver Cancer Risk - a Meta-analysis. Asian Pac J Cancer Prev, 13, 2841-6.
  13. Mandal RK, Mittal RD (2010). Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population? Urol Oncol, 30, 555-61.
  14. Nunobiki O, Ueda M, Yamamoto M, et al (2010). MDM2 SNP 309 human papillomavirus infection in cervical carcinogenesis. Gynecol Oncol, 118, 258-61.
  15. Ohmiya N, Taguchi A, Mabuchi N, et al (2006). MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis. J Clin Oncol, 24, 4434-40.
  16. Stoehr R, Hitzenbichler F, Kneitz B, et al (2008). Mdm2- SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics. Br J Cancer, 99, 78-82.
  17. Sun T, Lee GS, Oh WK, et al (2010). Single-nucleotide polymorphisms in p53 pathway and aggressiveness of prostate cancer in a Caucasian population. Clin Cancer Res, 16, 5244-51.
  18. Vassilev LT, Vu BT, Graves B, et al (2004). In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303, 844-8.
  19. Xu B, Xu Z, Cheng G, et al (2010). Association between polymorphisms of TP53 and MDM2 and prostate cancer risk in southern Chinese. Cancer Genet Cytogenet, 202, 76-81.
  20. Yoon YJ, Chang HY, Ahn SH, et al (2008). MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis, 29, 1192-6.

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