DOI QR코드

DOI QR Code

MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions

  • Published : 2015.09.02

Abstract

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also strongly associated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthy controls was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing. Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to those with the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in females by ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone; however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95% CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dose-dependent increase in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India.

References

  1. Cai K, Wang Y, Zhao X, et al (2014). Association between the P53 codon 72 polymorphism and nasopharyngeal cancer risk. Tumour Biol, 35, 1891-7. https://doi.org/10.1007/s13277-013-1254-5
  2. Cancer IAfRo, Humans IWGotEoCRt 2004. IARC monographs on the evaluation of carcinogenic risks to humans, IARC.
  3. Chakrobarty B, Roy JG, Majumdar S, et al (2014). Relationship among tobacco habits, human papilloma virus (HPV) infection, p53 polymorphism/mutation and the risk of oral squamous cell carcinoma. J Oral Maxillofac Pathol, 18, 211-6. https://doi.org/10.4103/0973-029X.140752
  4. Choudhury JH, Ghosh SK (2014). Gene-environment interaction and susceptibility in head and neck cancer patients and in their first-degree relatives: a study of Northeast Indian population. J Oral Pathol Med, [Epub ahed of print].
  5. Dikshit R, Gupta PC, Ramasundarahettige C, et al (2012). Cancer mortality in India: a nationally representative survey. Lancet, 379, 1807-16. https://doi.org/10.1016/S0140-6736(12)60358-4
  6. 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.
  7. Joshi P, Dutta S, Chaturvedi P, et al (2014). Head and neck cancers in developing countries. Rambam Maimonides Med J, 5, 9.
  8. 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. https://doi.org/10.7314/APJCP.2012.13.6.2841
  9. Macha MA, Rachagani S, Pai P, et al (2014). MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway. Oncogene, [Epub ahead of print].
  10. Moradi MT, Salehi Z, Aminian K, et al (2014). Effects of p53 codon 72 and MDM2 SNP309 polymorphisms on gastric cancer risk among the Iranian population. Asian Pac J Cancer Prev, 15, 7413-7. https://doi.org/10.7314/APJCP.2014.15.17.7413
  11. Nagata T, Shirakawa K, Kobayashi N, et al (2014). Structural basis for inhibition of the MDM2:p53 interaction by an optimized MDM2-binding peptide selected with mRNA display. PLoS One, 9, 109163. https://doi.org/10.1371/journal.pone.0109163
  12. Riaz N, Morris LG, Lee W, et al (2014). Unraveling the molecular genetics of head and neck cancer through genomewide approaches. Genes Dis, 1, 75-86. https://doi.org/10.1016/j.gendis.2014.07.002
  13. Rothenberg SM, Ellisen LW (2012). The molecular pathogenesis of head and neck squamous cell carcinoma. J Clin Invest, 122, 1951-7. https://doi.org/10.1172/JCI59889
  14. Song B, Duan ZY, Zhong YH, et al (2014). Meta-analysis of the MDM2 T309G polymorphism and gastric cancer risk. Asian Pac J Cancer Prev, 14, 6649-51.
  15. Suresh K, Chandirasekar R, Kumar BL, et al (2010). No association between the Trp53 codon 72 polymorphism and head and neck cancer: a case-control study in a South Indian population. Asian Pac J Cancer Prev, 11, 1749-53.
  16. Talukdar FR, Ghosh SK, Laskar RS, et al (2013). Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. PLoS One, 8, 60996. https://doi.org/10.1371/journal.pone.0060996
  17. Tang T, Song X, Yang Z, et al (2014). Association between murine double minute 2 T309G polymorphism and risk of liver cancer. Tumour Biol, 35, 11353-7. https://doi.org/10.1007/s13277-014-2432-9
  18. Wan Y, Wu W, Yin Z, et al (2011). MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated metaanalysis. BMC Cancer, 11, 208. https://doi.org/10.1186/1471-2407-11-208
  19. Wang W, Du M, Gu D, et al (2014). MDM2 SNP309 polymorphism is associated with colorectal cancer risk. Sci Rep, 4, 4851.
  20. Xiao M, Zhang L, Zhu X, et al (2010). Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population. BMC Cancer, 10, 147. https://doi.org/10.1186/1471-2407-10-147
  21. Yan YL, Han F, Tan WM, et al (2014). Association between the MDM2 T309G polymorphism and leukemia risk: a metaanalysis. Asian Pac J Cancer Prev, 15, 6767-72. https://doi.org/10.7314/APJCP.2014.15.16.6767

Cited by

  1. BRCA1 and MDM2 as independent blood-based biomarkers of head and neck cancer vol.37, pp.12, 2016, https://doi.org/10.1007/s13277-016-5359-5
  2. Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis vol.5, pp.1, 2016, https://doi.org/10.1186/s40064-016-1858-5
  3. Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients vol.39, pp.5, 2017, https://doi.org/10.1177/1010428317699113