Association between the MDM2 T309G Polymorphism and Leukemia Risk: a Meta-analysis

  • Yan, Yu-Lan (Department of Clinical Laboratory, Affiliated Hospital of Hainan Medical College) ;
  • Han, Feng (Department of Clinical Laboratory, Affiliated Hospital of Hainan Medical College) ;
  • Tan, Wen-Min (Department of Clinical Laboratory, Affiliated Hospital of Hainan Medical College) ;
  • Wu, Cui-Ping (Department of Clinical Laboratory, Affiliated Hospital of Hainan Medical College) ;
  • Qin, Xi (Department of Clinical Laboratory, Affiliated Hospital of Hainan Medical College)
  • Published : 2014.08.30


Several studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and leukemia risk, but they reported contradictory results. For better understanding of the effect of MDM2 T309G polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature (CBM) databases before May 2014. Assessment of associations between the MDM2 T309G polymorphism and leukemia risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of 11 publications covering 12 case-control studies with 2, 362 cases and 5, 562 controls concerning MDM2 T309G polymorphism with respect to leukemia were included in the meta-analysis. Significant associations were found between MDM2 T309G polymorphism and leukemia risk in four models in overall populations (G vs T: OR=1.29, 95% CI=1.11-1.49, p=0.001; GG vs TT: OR=1.67, 95% CI=1.21-2.30, p=0.002; GG vs TG/TT: OR=1.56, 95% CI=1.21-2.00, p=0.001; GG/TG vs TT: OR=1.28, 95% CI=1.05-1.57, p=0.015). In the sub-group analysis according to ethnicity, increased leukemia risks were observed in three genetic models among Asians but not Caucasians. In conclusion, the results of our meta-analysis suggest that the MDM2 T309G polymorphism can increase the risk of leukemia, especially among Asian populations.




  1. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101.
  2. Bjork J, Johansson B, Broberg K, Albin M (2009). Smoking as a risk factor for myelodysplastic syndromes and acute myeloid leukemia and its relation to cytogenetic findings: a case-control study. Leuk Res, 33, 788-91.
  3. 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.
  4. Chen J, Zhu B, Li Y (2013). Genetic variations in MDM2 and P53 genes confer risk for adult acute lymphoblastic leukemia in a Chinese population. DNA Cell Biol, 32, 414-9.
  5. Chen QW, Chen H, Cheng JS, Meng ZQ (2014). MDM2 SNP309T>G polymorphism and hepatocellular carcinoma risk: a meta-analysis. Tumour Biol, 35, 4147-51.
  6. Chen W, Wu Q, Ren H (2014). Meta-analysis of associations between MDM2 SNP309 polymorphism and gastric cancer risk. Biomed Rep, 2, 105-11.
  7. Chen YL, Chang YS, Chang JG, Wu SM (2009). Genotyping of single nucleotide polymorphism in MDM2 genes by universal fluorescence primer PCR and capillary electrophoresis. Anal Bioanal Chem, 394, 1291-7.
  8. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  9. Do TN, Ucisik-Akkaya E, Davis CF, Morrison BA, Dorak MT (2009). TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility. Cancer Genet Cytogenet, 195, 31-6.
  10. Dong HJ, Fang C, Fan L, et al (2012). MDM2 promoter SNP309 is associated with an increased susceptibility to chronic lymphocytic leukemia and correlates with MDM2 mRNA expression in Chinese patients with CLL. Int J Cancer, 130, 2054-61.
  11. Ebid GT, Sedhom IA, El-Gammal MM, Moneer MM (2012). MDM2 T309G has a synergistic effect with P21 ser31arg single nucleotide polymorphisms on the risk of acute myeloid leukemia. Asian Pac J Cancer Prev, 13, 4315-20.
  12. Egger M, Davey Smith G, Schneider M, Minder C (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.
  13. Ellis NA, Huo D, Yildiz O, et al (2008). MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility. Blood, 112, 741-9.
  14. Estey EH (2001). Prognostic factors in acute myelogenous leukemia. Leukemia, 15, 670-2.
  15. Finch SC (2007). Radiation-induced leukemia: lessons from history. Best Pract Res Clin Haematol, 20, 109-18.
  16. Gamazon ER, Lamba JK, Pounds S, et al (2013). Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients. Blood, 121, 4366-76.
  17. Gao J, Kang AJ, Lin S, et al (2014). Association between MDM2 rs 2279744 polymorphism and breast cancer susceptibility: a meta-analysis based on 9, 788 cases and 11, 195 controls. Ther Clin Risk Manag, 10, 269-77.
  18. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21, 1539-58.
  19. Jiang D, Hong Q, Shen Y, et al (2014). The diagnostic value of DNA methylation in leukemia: a systematic review and metaanalysis. PLoS One, 9, e96822.
  20. Lichtman MA (2010). Obesity and the risk for a hematological malignancy: leukemia, lymphoma, or myeloma. Oncologist, 15, 1083-101.
  21. Liu J, Zheng Y, Lei D, et al (2011). MDM2 309T>G polymorphism and risk of squamous cell carcinomas of head and neck: a metaanalysis. Asian Pac J Cancer Prev, 12, 1899-903.
  22. Liu YC, Hsiao HH, Yang WC, et al (2013). MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: The association between MDM2 promoter genotype and disease susceptibility, age of onset, and blastfree survival in chronic phase patients receiving imatinib. Mol Carcinog, [Epub ahead of print].
  23. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  24. Mullighan CG (2010). Genetic variation and the risk of acute lymphoblastic leukemia. Leuk Res, 34, 1269-70.
  25. Peng Q, Mo C, Qin A, et al (2013). MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility: evidence from a meta-analysis. J Exp Clin Cancer Res, 32, 85.
  26. Phang BH, Linn YC, Li H, Sabapathy K (2008). MDM2 SNP309 G allele decreases risk but does not affect onset age or survival of Chinese leukaemia patients. Eur J Cancer, 44, 760-6.
  27. Phillips CL, Gerbing R, Alonzo T, et al (2010). MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer, 55, 248-53.
  28. Picksley SM, Lane DP (1993). The p53-mdm2 autoregulatory feedback loop: a paradigm for the regulation of growth control by p53? Bioessays, 15, 689-90.
  29. Poyurovsky MV, Katz C, Laptenko O, et al (2010). The C terminus of p53 binds the N-terminal domain of MDM2. Nat Struct Mol Biol, 17, 982-9.
  30. Qin X, Peng Q, Tang W, et al (2013). An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk. PLoS One, 8, e76031.
  31. Ross JA (2008). Environmental and genetic susceptibility to MLLdefined infant leukemia. J Natl Cancer Inst Monogr, 39, 83-6.
  32. Tang J, Shen L, Song S, An Z, Zhang C (2014). Polymorphisms in the MDM2 gene and risk of malignant bone tumors: a metaanalysis. Tumour Biol, 35, 779-84.
  33. Vardiman JW, Thiele J, Arber DA, et al (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937-51.
  34. Wang J, Yang YG, Zhou M, et al (2013). Meta-analysis of randomised clinical trials comparing idarubicin + cytarabine with daunorubicin + cytarabine as the induction chemotherapy in patients with newly diagnosed acute myeloid leukaemia. PLoS One, 8, e60699.
  35. Wang L, Liu Z, Jing P, et al (2014). Effects of murine double minute 2 polymorphisms on the risk and survival of osteosarcoma: a systemic review and meta-analysis. Tumour Biol, 35, 1649-52.
  36. Xiong X, Wang M, Wang L, et al (2009). Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. Leuk Res, 33, 1454-8.
  37. Yalcin A, Serin MS, Emekdas G, et al (2009). Promoter methylation of P15 (INK4B) gene is possibly associated with parvovirus B19 infection in adult acute leukemias. Int J Lab Hematol, 31, 407-19.
  38. Yan Y, Liang H, Li T, et al (2014). Association of XRCC3 Thr241Met polymorphism and leukemia risk: evidence from a meta-analysis. Leuk Lymphoma, 55, 2130-4.
  39. Yan Y, Liang H, Xie L, et al (2014). Association of MDR1 G2677T polymorphism and leukemia risk: evidence from a metaanalysis. Tumour Biol, 35, 2191-7.
  40. Zenz T, Habe S, Benner A, et al (2008). The MDM2 -309 T/G promoter single nucleotide polymorphism does not alter disease characteristics in chronic lymphocytic leukemia. Haematologica, 93, 1111-3.

Cited by

  1. MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions vol.16, pp.14, 2015,
  2. Role of the MDM2 Promoter Polymorphism (-309T>G) in Acute Myeloid Leukemia Development vol.16, pp.7, 2015,