Effects of p53 Codon 72 and MDM2 SNP309 Polymorphisms on Gastric Cancer Risk among the Iranian Population

  • Published : 2014.09.15


Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.


  1. Atrkar-Roushan Z, Kazemnejad A, Mansour-Ghanaei F, et al (2013). Trend analysis of gastrointestinal cancer incidences in guilan province: comparing rates over 15 years. Asian Pac J Cancer Prev, 14, 7587-93.
  2. Bond GL, Hu W, Bond EE, et al (2004). A single nucleotide polymorphism in the< i> 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 (2005a). A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res, 65, 5481-4.
  4. Bond GL, Hu W, Levine AJ (2005b). MDM2 is a central node in the p53 pathway: 12 years and counting. Current Cancer Drug Targets, 5, 3-8.
  5. Fakharzadeh S, Trusko S, George D (1991). Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J, 10, 1565.
  6. Fallah M (2007). Cancer incidence in five provinces of Iran: Ardebil, Gilan, Mazandaran, Golestan and Kerman, 1996-2000.
  7. Hamajima N, Matsuo K, Suzuki T, et al (2002). No associations of< i> p73 G4C14-to-A4T14 at exon 2 and< i> p53 Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese. Cancer letters, 181, 81-5.
  8. Harris CC, Hollstein M (1993). Clinical implications of the p53 tumor-suppressor gene. New Engl J Med, 329, 1318-27.
  9. Harris N, Brill E, Shohat O, et al (1986). Molecular basis for heterogeneity of the human p53 protein. Molecular Cellular Biol, 6, 4650-6.
  10. Ko LJ, Prives C (1996). p53: puzzle and paradigm. Genes Development, 10, 1054-72.
  11. Liu K-J, Qi H-Z, Yao H-L, et al (2012). An updated meta-analysis of the p53 codon 72 polymorphism and gastric cancer risk. Molecular Biology Reports, 39, 8265-75.
  12. Marine J-C, Francoz S, Maetens M, et al (2006). Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4. Cell Death Differentiation, 13, 927-34.
  13. Matlashewski G, Tuck S, Pim D, et al (1987). Primary structure polymorphism at amino acid residue 72 of human p53. Molecular Cellular Biol, 7, 961-3.
  14. Menin C, Scaini MC, De Salvo GL, et al (2006). Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer Inst, 98, 285-8.
  15. Mojtahedi Z, Haghshenas M, Hosseini S, et al (2010). p 53 codon 72 polymorphism in stomach and colorectal adenocarcinomas in Iranian patients. Indian J Cancer, 47, 31.
  16. Momand J, Zambetti GP, Olson DC, et al (1992). The< i> mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69, 1237-45.
  17. Moradi MT, Salehi Z, Asl SF, et al (2013). Helicobacter pylori infection and MDM2 SNP309 association with gastric cancer susceptibility. Genet Test Mol Biomarkers, 17, 794-8.
  18. Oh MG, Kim JH, Han MA, et al (2014). Family history and survival of patients with gastric cancer: a meta-analysis. Asian Pac J Cancer Prev, 15, 3465-70.
  19. 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.
  20. Pei D, Zhang Y, Zheng J (2012). Regulation of p53: a collaboration between Mdm2 and Mdmx. Oncotarget, 3, 228.
  21. Poyurovsky MV, Prives C (2006). Unleashing the power of p53: lessons from mice and men. Genes Development, 20, 125-31.
  22. Ren Y-W, Yin Z-H, Wan Y, et al (2013). P53 Arg72Pro and MDM2 SNP309 polymorphisms cooperate to increase lung adenocarcinoma risk in Chinese female non-smokers: A Case Control Study. Asian Pac J Cancer Prev, 14, 5415-20.
  23. Sadeghi RN, Damavand B, Vahedi M, et al (2013). Detection of p53 common intron polymorphisms in patients with gastritis lesions from Iran. Asian Pac J Cancer Prev, 14, 91-6.
  24. Sakamuro D, Sabbatini P, White E, et al (1997). The polyproline region of p53 is required to activate apoptosis but not growth arrest. Oncogene, 15, 887-98.
  25. Somi MH, Golzari M, Farhang S, et al (2014). Gastrointestinal cancer incidence in East Azerbaijan, Iran: update on 5 year incidence and trends. Asian Pac J Cancer Prev, 15, 3945.
  26. Song B, Duan Z-Y, Zhong Y-H, et al (2013). Meta-analysis of the MDM2 T309G polymorphism and gastric cancer risk. Asian Pac J Cancer Prev: APJCP, 14, 6649-51.
  27. Storey A, Thomas M, Kalita A, et al (1998). Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature, 393, 229-34.
  28. Tahara E (1993). Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol, 119, 265-72.
  29. Tian X, Tian Y, Ma P, et al (2013). Association between MDM2 SNP309 T> G and risk of gastric cancer: a meta-analysis. Asian Pac J Cancer Prev, 14, 1925-9.
  30. Vogelstein B, Lane D, Levine AJ (2000). Surfing the p53 network. Nature, 408, 307-10.
  31. Wade M, Wang YV, Wahl GM (2010). The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol, 20, 299-309.
  32. Walker KK, Levine AJ (1996). Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Academy of Sciences, 93, 15335-40.
  33. Whibley C, Pharoah PD, Hollstein M (2009). p53 polymorphisms: cancer implications. Nature Reviews Cancer, 9, 95-107.
  34. Wo X, Han D, Sun H, et al (2011). < i> MDM2 SNP309 contributes to tumor susceptibility: A meta-analysis. J Genetics Genomics, 38, 341-50.
  35. Zhou Y, Li N, Zhuang W, et al (2010). p53 Codon 72 polymorphism and gastric cancer risk in a Chinese Han population. Genetic Testing Molecular Biomarkers, 14, 829-33.

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. Genetic Polymorphism of MDM2 SNP309 in Patients with Helicobacter Pylori-Associated Gastritis vol.16, pp.16, 2015,
  3. Correlation between Patterns of Mdm2 SNIP 309 and Histopathological Severity of Helicobacter pylori Associated Gastritis in Thailand vol.16, pp.17, 2015,
  4. Role of the Mdm2 SNIP 309 Polymorphism in Gastric Mucosal Morphologic Patterns of Patients with Helicobacter pylori Associated Gastritis vol.17, pp.3, 2016,
  5. No association of TP53 codon 72 and intron 3 16-bp duplication polymorphisms with breast cancer risk in Chinese Han women: new evidence from a population-based case–control investigation vol.23, pp.1, 2018,
  6. Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation vol.120, pp.3, 2018,