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Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 Genes in Combination with the MTHFR C677T Genetic Polymorphism in Gastric Cancer

  • Xiong, Hai-Lin (Department of Medical Oncology, Huizhou Municipal Central Hospital) ;
  • Liu, Xun-Qi (Department of Medical Oncology, Huizhou Municipal Central Hospital) ;
  • Sun, Ai-Hua (Department of Medical Oncology, Huizhou Municipal Central Hospital) ;
  • He, Ying (Department of Medical Oncology, Huizhou Municipal Central Hospital) ;
  • Li, Jun (Department of Medical Oncology, Huizhou Municipal Central Hospital) ;
  • Xia, Yuan (Department of Medical Oncology, Huizhou Municipal Central Hospital)
  • Published : 2013.05.30

Abstract

Associations of P16, MGMT, hMLH1 and hMLH2 with gastric cancer and their relation with MTHFR status in gastric patients who were confirmed with pathological diagnosis were assessed. Aberrant DNA methylation of P16, MGMT, hMLH1 and hMLH2 and polymorphisms of MTHFR C677T were assayed. The proportional DNA hypermethylation in P16, MGMT, hMLH1 and hMLH2 in cancer tissues was significantly higher than in remote normal-appearing tissues. DNA hypermethylation of P16 and MGMT was correlated with the T and N stages. Individuals with homozygotes (TT) of MTHFR C677T had significant risk of hypermethylation of MGMT in cancer tissues [OR (95% CI)= 3.47(1.41-7.93)]. However, we did not find association between polymorphism in MTHFR C677T and risk of hypermethylation in P16, MGMT, hMLH1 and hMLH2 genes either in cancer or remote normal-appearing tissues. Aberrant hypermethylation of P16, MGMT, hMLH1 and hMLH2 could be predictive of gastric cancer.

Keywords

Aberrant DNA methylation;P16;MGMT;hMLH1;hMLH2;gastric cancer

References

  1. Aune D, Deneo-Pellegrini H, Ronco AL, et al (2011). Dietary folate intake and the risk of 11 types of cancer: a case-control study in Uruguay. Ann Oncol, 22, 444-51. https://doi.org/10.1093/annonc/mdq356
  2. Bagley PJ, Selhub J (1998). A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci U S A, 95, 13217-20. https://doi.org/10.1073/pnas.95.22.13217
  3. Chen J, Huang ZJ, Duan YQ, et al (2012). Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism and folate intake in esophageal squamous cell carcinoma. Asian Pac J Cancer Prev, 13, 5303-6. https://doi.org/10.7314/APJCP.2012.13.10.5303
  4. Cheng H, Lu M, Mao LJ, et al (2012). Relationships among MTHFR a1298c gene polymorphisms and methylation status of Dact1 gene in transitional cell carcinomas. Asian Pac J Cancer Prev, 13, 5069-74. https://doi.org/10.7314/APJCP.2012.13.10.5069
  5. de Cassia Carvalho Barbosa R, da Costa DM, Cordeiro DE, et al (2012). Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil. Anticancer Res, 32, 4805-11.
  6. Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 10, 111-3. https://doi.org/10.1038/ng0595-111
  7. Gao S, Ding LH, Wang JW, et al (2013). Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate reductase in association with the susceptibility to gastric cancer. Asian Pac J Cancer Prev, 14, 299-302. https://doi.org/10.7314/APJCP.2013.14.1.299
  8. Gius D, Bradbury CM, Sun L, et al (2005). The epigenome as a molecular marker and target. Cancer, 104, 1789-93. https://doi.org/10.1002/cncr.21395
  9. Gomes MV, Toffoli LV, Arruda DW, et al (2012). Age-related changes in the global DNA methylation profile of leukocytes are linked to nutrition but are not associated with the MTHFR C677T genotype or to functional capacities. PLoS One, 7,e52570. https://doi.org/10.1371/journal.pone.0052570
  10. Gotze T, Rocken C, Rohl FW, et al (2007). Gene polymorphisms of folate metabolizing enzymes and the risk of gastric cancer. Cancer Lett, 251, 228-36. https://doi.org/10.1016/j.canlet.2006.11.021
  11. International Agency for Research on Cancer (2008). Globocan 2008: Stomach Cancer incidence, Mortality and Prevalence Worldwide in 2008. IARC.
  12. International Agency for Research on Cancer (1994). IARC working group on the evaluation of carcinogenic risks to humans, schistosomes, liver flukes, Helicobacter pylori. IARC monographs on the evaluation of carcinogenic risks to humans, vol 61. International Agency for Research on Cancer, Lyon. 1-241.
  13. Issa JP, Garcia-Manero G, Giles FJ, et al (2004). Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. Blood, 103, 1635-40. https://doi.org/10.1182/blood-2003-03-0687
  14. Jones PA, Baylin SB (2007). The epigenomics of cancer. Cell, 128, 683-92. https://doi.org/10.1016/j.cell.2007.01.029
  15. Miao X, Xing D, Tan W, et al (2002). Susceptibility to gastric cardia adenocarcinoma and genetic polymorphism in methylenetetrahydrofolate reductase in an at-risk Chinese population. Cancer Epidemiol Biomarkers Prev, 11, 1454-8.
  16. Neves Filho EH, Alves MK, Lima VP, et al (2010). MTHFR C677T polymorphism and differential methylation status in gastric cancer: an association with Helicobacter pylori infection. Virchows Arch, 457, 627-33. https://doi.org/10.1007/s00428-010-0996-3
  17. Momparler RL, Bovenzi V (2000). DNA methylation and cancer. J Cell Physiol, 183, 145-54. https://doi.org/10.1002/(SICI)1097-4652(200005)183:2<145::AID-JCP1>3.0.CO;2-V
  18. Sato F, Meltzer SJ (2006). CpG island hypermethylation in progression of esophageal and gastric cancer. Cancer, 106, 483-93. https://doi.org/10.1002/cncr.21657
  19. Saberi S, Zendehdel K, Jahangiri S, et al (2012). Impact of methylenetetrahydrofolate reductase C677T polymorphism on the risk of gastric cancer and its interaction with Helicobacter pylori infection. Iran Biomed J, 16, 179-84.
  20. Wang J, Sasco AJ, Fu C, et al (2008). Aberrant DNA Methylation of P16, MGMT, and hMLH1 Genes in Combination with MTHFR C677T Genetic Polymorphism in Esophageal Squamous Cell Carcinoma. Cancer Epidemiol Biomarkers Prev, 17, 118-25. https://doi.org/10.1158/1055-9965.EPI-07-0733

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