Tumor Biology

, Volume 35, Issue 4, pp 3431–3438 | Cite as

MDM2 SNP309 is an ethnicity-dependent risk factor for digestive tract cancers

  • Bo Chen
  • Lei Cao
  • Kong-Wang Hu
  • Jia-Wei Zhang
  • Xiang-Ling Meng
  • Mao-Ming Xiong
Research Article


Published data on the relationship between T309G polymorphism in the murine double minute 2 (MDM2) gene and susceptibility of digestive tract cancers (DTC) are inconclusive. Thus, the aim of this study is to determine whether MDM2 T309G polymorphism is associated with the risk of diverse DTC, including esophagus, stomach, liver, bile duct, pancreas, and colorectum cancers. Relevant studies were identified up to October 1, 2013. Crude odds ratio (OR) and 95 % confidence interval (CI) were used as a measure of the strength of the association. The pooled result based on all studies showed that there was a statistically significant link between MDM2 T309G polymorphism and DTC susceptibility (T vs. G: OR = 0.82, 95%CI = 0.76–0.88). When stratified by race, significant associations were observed for all genetic models among Asians (especially in Chinese population), but not among Caucasians. Subgroup analyses according to tumor location indicated that the genetic variant was associated with esophageal (OR = 0.88, 95%CI = 0.81–0.96 for T vs. G), hepatocellular (OR = 0.69, 95%CI = 0.57–0.84 for T vs. G) and pancreatic cancer risk but not associated with cholangiocarcinoma or colorectum cancer susceptibility. Meanwhile, the G allele was also suggested to be associated with increased gastric cancer risk (OR = 0.68, 95%CI = 0.54–0.87 for TT + TG vs. GG for intestinal type of gastric cancer and OR = 0.18, 95%CI = 0.06–0.50 for TT vs. GG for Helicobacter pylori infection positive stomach cancer). Our study indicates that the MDM2 T309G polymorphism may be an ethnicity-dependent risk factor for DTC, especially for the upper gastrointestinal tract malignancies.


Digestive tract cancer MDM2 Polymorphism Susceptibility Risk factor 


Conflicts of interest


Supplementary material

13277_2013_1453_MOESM1_ESM.doc (108 kb)
ESM 1 (DOC 107 kb)
13277_2013_1453_MOESM2_ESM.doc (126 kb)
ESM 2 (DOC 126 kb)


  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Wei WQ, Yang J, Zhang SW, Chen WQ, Qiao YL. Esophageal cancer mortality trends during the last 30 years in high risk areas in china: comparison of results from national death surveys conducted in the 1970's, 1990's and 2004–2005. Asian Pac J Cancer Prev. 2011;12:1821–6.PubMedGoogle Scholar
  4. 4.
    Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–87.PubMedCrossRefGoogle Scholar
  5. 5.
    Haas SL, Ye W, Lohr JM. Alcohol consumption and digestive tract cancer. Curr Opin Clin Nutr Metab Care. 2012;15:457–67.PubMedCrossRefGoogle Scholar
  6. 6.
    Pelucchi C, Bosetti C, Rossi M, Negri E, La Vecchia C. Selected aspects of Mediterranean diet and cancer risk. Nutr Cancer. 2009;61:756–66.PubMedCrossRefGoogle Scholar
  7. 7.
    Oren M, Damalas A, Gottlieb T, Michael D, Taplick J, Leal JF, et al. Regulation of p53: intricate loops and delicate balances. Biochem Pharmacol. 2002;64:865–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Bouska A, Lushnikova T, Plaza S, Eischen CM. MDM2 promotes genetic instability and transformation independent of p53. Mol Cell Biol. 2008;28:4862–74.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Lalonde ME, Ouimet M, Lariviere M, Kritikou EA, Sinnett D. Identification of functional DNA variants in the constitutive promoter region of MDM2. Hum Genomics. 2012;6:15.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Pan X, Li Y, Feng J, Wang X, Hao B, Shi R, et al. A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients. BMC Cancer. 2013;13:126.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Yang Y, Xia T, Li N, Zhang J, Cong W, Deng Q, et al. Combined effects of P53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis b virus-related hepatocellular carcinoma. Protein Cell. 2013;4:71–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Wroblewski LE, Peek Jr RM, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23:713–39.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Micel LN, Tentler JJ, Smith PG, Eckhardt GS. Role of ubiquitin ligases and the proteasome in oncogenesis: novel targets for anticancer therapies. J Clin Oncol. 2013;31:1231–8.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Di J, Zhang Y, Zheng J. Reactivation of p53 by inhibiting MDM2 E3 ligase: a novel antitumor approach. Curr Cancer Drug Targets. 2011;11:987–94.PubMedCrossRefGoogle Scholar
  15. 15.
    Acun T, Terzioglu-Kara E, Konu O, Ozturk M, Yakicier MC. MDM2 SNP309 G allele displays high frequency and inverse correlation with somatic p53 mutations in hepatocellular carcinoma. Mutat Res. 2010;684:106–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Qin X, Peng Q, Tang W, Lao X, Chen Z, Lai H, et al. An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk. PLoS One. 2013;8:e76031.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Yang J, Liu B, Li W, Xiong H, Qiu H, Fu Q, et al. Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC). Cancer Epidemiol. 2013;37:629–33.PubMedCrossRefGoogle Scholar
  18. 18.
    Jin L, Sturgis EM, Zhang Y, Huang Z, Wei P, Guo W, et al. Genetic variants in p53-related genes confer susceptibility to second primary malignancy in patients with index squamous cell carcinoma of head and neck. Carcinogenesis. 2013;34:1551–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Wang Z, Sturgis EM, Zhang Y, Huang Z, Zhou Q, Wei Q, et al. Combined p53-related genetic variants together with hpv infection increase oral cancer risk. Int J Cancer. 2012;131:E251–8.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Zhang Y, Bai Y, Guan J, Chen L. The MDM2 309 T/G polymorphism is associated with head and neck cancer risk especially in nasopharyngeal cancer: a meta-analysis. Onkologie. 2012;35:666–70.PubMedCrossRefGoogle Scholar
  21. 21.
    Li Y, Zhao H, Sun L, Huang L, Yang Q, Kong B. MDM2 SNP309 is associated with endometrial cancer susceptibility: a meta-analysis. Hum Cell. 2011;24:57–64.PubMedCrossRefGoogle Scholar
  22. 22.
    Chen B, Zhou Y, Yang P, Wu XT. Polymorphisms of xrcc1 and gastric cancer susceptibility: a meta-analysis. Mol Biol Rep. 2012;39:1305–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Zhang X, Zhang Y, Gu D, Cao C, Zhang Q, Xu Z, et al. Increased risk of developing digestive tract cancer in subjects carrying the plce1 rs2274223 A > G polymorphism: evidence from a meta-analysis. PLoS One. 2013;8:e76425.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Department of NeurologyThe Second Affiliated Hospital of Anhui Medical UniversityHefeiChina

Personalised recommendations