Skip to main content
Log in

Association between MTHFR C677T polymorphism and thyroid cancer risk: a meta-analysis

  • Research Article
  • Published:
Tumor Biology

Abstract

In the light of the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and thyroid cancer (TC) exist objection, a meta-analysis of the MTHFR C677T polymorphism with thyroid cancer risk was performed. All the available studies were identified through a search of the PubMed, Embase, Web of Science, and Chinese Biomedical Literature Database (CBM) up to March 2014. The association between the MTHFR C677T polymorphism and thyroid cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of five independent studies with 2,554 cases and 2,671 controls were included in our meta-analysis. Significant association was found between MTHFR C677T polymorphism and thyroid cancer risk in recessive model in overall populations (TT vs. TC/CC: OR = 1.88, 95 % CI = 1.59–2.21, P = 0.00), but there was no association between MTHFR C677T polymorphism and thyroid cancer risk found in other four models in overall populations (T vs. C: OR = 1.25, 95 % CI = 0.96–1.62, P = 0.10; TT vs. CC: OR = 1.11, 95 % CI = 0.93–1.33, P = 0.26; TC vs. CC: OR = 1.23, 95 % CI = 0.84–1.82, P = 0.29; TT/TC vs. CC: OR = 1.28, 95 % CI = 0.89–1.84, P = 0.19). In the subgroup analysis base on the ethnicity, the results suggested that MTHFR C677T polymorphism was significantly associated with thyroid cancer risk both in Caucasian and Asian populations in recessive model: (Caucasians: TT vs. TC/CC: OR = 2.28, 95 % CI = 1.11–4.67, P = 0.025; Asians: TT vs. TC/CC: OR = 1.86, 95 % CI = 1.57–2.20, P = 0.00). In conclusions, our meta-analysis suggested that the MTHFR C677T polymorphism is associated with thyroid cancer both in Caucasians and Asians.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295(18):2164–7.

    Article  CAS  PubMed  Google Scholar 

  3. Kilfoy BA, Devesa SS, Ward MH, Zhang Y, Rosenberg PS, et al. Gender is an age-specific effect modifier for papillary cancers of the thyroid gland. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1092–100.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.

    Article  CAS  PubMed  Google Scholar 

  5. Akslen LA, Haldorsen T, Thoresen SO, Glattre E. Survival and causes of death in thyroid cancer: a population-based study of 2,479 cases from Norway. Cancer Res. 1991;51(4):1234–41.

    CAS  PubMed  Google Scholar 

  6. Gilfillan CP. Review of the genetics of thyroid tumours: diagnostic and prognostic implications. ANZ J Surg. 2010;80(1–2):33–40.

    Article  PubMed  Google Scholar 

  7. Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid. 2011;21(2):125–34.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Imaizumi M, Usa T, Tominaga T, Neriishi K, Akahoshi M, et al. Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55–58 years after radiation exposure. JAMA. 2006;295(9):1011–22.

    Article  CAS  PubMed  Google Scholar 

  9. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569–80.

    Article  CAS  PubMed  Google Scholar 

  10. Landa I, Ruiz-Llorente S, Montero-Conde C, Inglada-Perez L, Schiavi F, et al. The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. PLoS Genet. 2009;5(9):e1000637.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Du Y, Han LY, Li DD, Liu H, Gao YH, et al. Associations between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and risk of differentiated thyroid carcinoma: a meta-analysis. Asian Pac J Cancer Prev. 2013;14(9):5483–7.

    Article  PubMed  Google Scholar 

  12. Yamada K, Chen Z, Rozen R, Matthews RG. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci U S A. 2001;98(26):14853–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Hasoun LZ, Bailey SW, Outlaw KK, Ayling JE. Effect of serum folate status on total folate and 5-methyltetrahydrofolate in human skin. Am J Clin Nutr. 2013;98(1):42–8.

    Article  CAS  PubMed  Google Scholar 

  14. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111–3.

    Article  CAS  PubMed  Google Scholar 

  15. Bagley PJ, Selhub J. 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. 1998;95(22):13217–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93(1):7–9.

    Article  CAS  PubMed  Google Scholar 

  17. Kweon S-S, Shin M-H, Kim H-N, Kim S-H, Kang H-C. Polymorphisms of methylenetetrahydrofolate reductase and glutathione S- transferase are not associated with the risk of papillary thyroid cancer in Korean population. Mol Biol Rep. 2014. doi:10.1007/s11033-11014-13245-z.

    PubMed  Google Scholar 

  18. Ozdemir S, Silan F, Hasbek Z, Uludag A, Atik S, et al. Increased T-allele frequency of 677 C > T polymorphism in the methylenetetrahydrofolate reductase gene in differentiated thyroid carcinoma. Genet Test Mol Biomark. 2012;16(7):780–4.

    Article  CAS  Google Scholar 

  19. Prasad VV, Wilkhoo H. Association of the functional polymorphism C677T in the methylenetetrahydrofolate reductase gene with colorectal, thyroid, breast, ovarian, and cervical cancers. Onkologie. 2011;34(8–9):422–6.

    Article  CAS  PubMed  Google Scholar 

  20. Fard-Esfahani P, Fard-Esfahani A, Saidi P, Fayaz S, Mohabati R, et al. An increased risk of differentiated thyroid carcinoma in Iran with the 677C–T homozygous polymorphism in the MTHFR Gene. Cancer Epidemiol. 2011;35(1):56–8.

    Article  CAS  PubMed  Google Scholar 

  21. Siraj AK, Ibrahim M, Al-Rasheed M, Abubaker J, Bu R, et al. Polymorphisms of selected xenobiotic genes contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. BMC Med Genet. 2008;9:61.

    Article  PubMed Central  PubMed  Google Scholar 

  22. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.

    Article  PubMed  Google Scholar 

  25. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xi Qin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yan, Y., Han, F., Fu, H. et al. Association between MTHFR C677T polymorphism and thyroid cancer risk: a meta-analysis. Tumor Biol. 35, 7707–7712 (2014). https://doi.org/10.1007/s13277-014-2038-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2038-2

Keywords

Navigation