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Tumor Biology

, Volume 35, Issue 5, pp 4943–4948 | Cite as

Positive association between MTHFR C677T polymorphism and oral cancer risk: a meta-analysis

Research Article

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a central enzyme involved in regulating the metabolic function of folate, which plays a pivotal role in DNA synthesis, repair, and methylation. The role of MTHFR C677T polymorphism in oral cancer risk has been reported with conflicting evidence. We conducted this study to appropriately estimate the effect size. We searched eligible studies in medicine-specific databases (PubMed, EMBASE, and Web of Knowledge) using (polymorphism) OR (polymorphisms) AND (methylenetetrahydrofolate reductase) OR (MTHFR) AND (oral cancer). A total of seven studies were summarized. This meta-analysis of the combined data showed a marginal association of MTHFR C677T polymorphism with oral cancer risk [odds ratio (OR) = 0.86, 95 % confidence interval (CI) = 0.73–1.00 for CT vs. CC]. We also found decreased oral cancer risk in Asian population and hospital-based studies. Moreover, heavy drinkers were found to have a significantly higher risk of developing such cancer as compared to the non-heavy drinkers. These results suggest that MTHFR C677T polymorphism may play a role in oral cancer carcinogenesis in Asian population and heavy drinkers.

Keywords

Meta-analysis MTHFR C677T polymorphism Oral cancer 

References

  1. 1.
    Blot WJ et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988;48(11):3282–7.PubMedGoogle Scholar
  2. 2.
    Hayes RB et al. Tobacco and alcohol use and oral cancer in Puerto Rico. Cancer Causes Control. 1999;10(1):27–33.CrossRefPubMedGoogle Scholar
  3. 3.
    Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Glade MJ. Food, nutrition, and the prevention of cancer: a global perspective. Nutrition. 1999;15(6):523–6. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997.CrossRefPubMedGoogle Scholar
  5. 5.
    Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000;130(2):129–32.PubMedGoogle Scholar
  6. 6.
    Giovannucci E et al. Alcohol, low-methionine–low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst. 1995;87(4):265–73.CrossRefPubMedGoogle Scholar
  7. 7.
    Jaskiewicz K et al. Association of esophageal cytological abnormalities with vitamin and lipotrope deficiencies in populations at risk for esophageal cancer. Anticancer Res. 1988;8(4):711–5.PubMedGoogle Scholar
  8. 8.
    Tseng M et al. Micronutrients and the risk of colorectal adenomas. Am J Epidemiol. 1996;144(11):1005–14.CrossRefPubMedGoogle Scholar
  9. 9.
    Blount BC et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997;94(7):3290–5.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kingsley K et al. Analysis of oral cancer epidemiology in the US reveals state-specific trends: implications for oral cancer prevention. BMC Public Health. 2008;8:87.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Marney AM et al. Endogenous bradykinin contributes to increased plasminogen activator inhibitor 1 antigen following hemodialysis. J Am Soc Nephrol. 2009;20(10):2246–52.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Masuda J, Nabika T, Notsu Y. Silent stroke: pathogenesis, genetic factors and clinical implications as a risk factor. Curr Opin Neurol. 2001;14(1):77–82.CrossRefPubMedGoogle Scholar
  13. 13.
    Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Zetterberg H et al. Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos. Eur J Hum Genet. 2002;10(2):113–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J. 2003;146(6):948–57.CrossRefPubMedGoogle Scholar
  16. 16.
    Galbiatti AL et al. Head and neck cancer: genetic polymorphisms and folate metabolism. Braz J Otorhinolaryngol. 2012;78(1):132–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee JE et al. Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case–control studies. Cancer Causes Control. 2012;23(4):537–45.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kiyohara C et al. Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case–control study in a Japanese population. BMC Cancer. 2011;11:459.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Gao CM et al. [MTHFR polymorphisms, dietary folate intake and risks to breast cancer]. Zhonghua Yu Fang Yi Xue Za Zhi. 2009;43(7):576–80.PubMedGoogle Scholar
  20. 20.
    Weinstein SJ et al. Folate intake, serum homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T genotype are not associated with oral cancer risk in Puerto Rico. J Nutr. 2002;132(4):762–7.PubMedGoogle Scholar
  21. 21.
    Solomon PR, Selvam GS, Shanmugam G. Polymorphism in ADH and MTHFR genes in oral squamous cell carcinoma of Indians. Oral Dis. 2008;14(7):633–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Higgins JP et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMedGoogle Scholar
  24. 24.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMedGoogle Scholar
  25. 25.
    Egger M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Liao, G., et al., Host genetic susceptibility to oral cancer: evidence from meta-analyses and pooled analyses. Oral Dis, 2013Google Scholar
  27. 27.
    Vairaktaris E et al. Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer. J Cancer Res Clin Oncol. 2006;132(4):219–22.CrossRefPubMedGoogle Scholar
  28. 28.
    Tsai CW et al. Methylenetetrahydrofolate reductase (MTHFR) genotype, smoking habit, metastasis and oral cancer in Taiwan. Anticancer Res. 2011;31(6):2395–9.PubMedGoogle Scholar
  29. 29.
    Supic G, Jovic N, Kozomara R, Zeljic K, Magic Z. Interaction between the MTHFR C677T polymorphism and alcohol—impact on oral cancer risk and multiple DNA methylation of tumor-related genes. J Dent Res. 2011;90(1):65–70.CrossRefPubMedGoogle Scholar
  30. 30.
    Sailasree R et al. Influence of methylenetetrahydrofolate reductase polymorphisms in oral cancer patients. J Oral Pathol Med. 2011;40(1):61–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Galbiatti AL et al. Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk. Mol Biol Rep. 2012;39(1):635–43.CrossRefPubMedGoogle Scholar
  32. 32.
    Vylliotis A et al. Effect of thrombosis-related gene polymorphisms upon oral cancer: a regression analysis. Anticancer Res. 2013;33(9):4033–9.PubMedGoogle Scholar
  33. 33.
    Duthie SJ et al. Folate, DNA stability and colo-rectal neoplasia. Proc Nutr Soc. 2004;63(4):571–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost. 1997;78(1):523–6.PubMedGoogle Scholar
  35. 35.
    Zhuo X et al. Polymorphisms of MTHFR C677T and A1298C association with oral carcinoma risk: a meta-analysis. Cancer Invest. 2012;30(6):447–52.CrossRefPubMedGoogle Scholar
  36. 36.
    Suzuki T, Matsuo K, Hasegawa Y, Hiraki A, Wakai K, Hirose K, et al. One-carbon metabolism-related gene polymorphisms and risk of head and neck squamous cell carcinoma: case–control study. Cancer Sci. 2007;98:1439–46.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Maxillofacial SurgeryAffiliated Hospital of Luzhou Medical CollegeLuzhouChina

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