Association between Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to cervical cancer: a meta-analysis

PLoS One. 2013;8(2):e55835. doi: 10.1371/journal.pone.0055835. Epub 2013 Feb 19.


Background: To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Methods: Based on comprehensive searches of the PubMed, Embase, and Web of Science databases, we identified outcome data from all articles estimating the association between MTHFR polymorphism and cervical cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results: A total of 12 studies with 2,924 cases (331 cervical intraepithelial neoplasia (CIN) I, 742 CIN II/III, 1851 invasive cervical cancer) and 2,581 controls were identified. There was no significant association between MTHFR C677T polymorphism and CIN I risk (T vs. C, OR = 1.10, 95% CI = 0.92-1.31; TT vs. CC, OR = 1.14, 95% CI = 0.78-1.68; TT+CT vs. CC, OR = 1.22, 95% CI = 0.94-1.58; TT vs. CT+CC, OR = 0.99, 95% CI = 0.70-1.40). For the CIN II/III, lack of an association was also found (T vs. C, OR = 1.08, 95% CI = 0.95-1.23; TT vs. CC, OR = 1.15, 95% CI = 0.87-1.52; TT+CT vs. CC, OR = 1.13, 95% CI = 0.94-1.35; TT vs. CT+CC, OR = 1.07, 95% CI = 0.83-1.38). The T allele had significant association to susceptibility of invasive cervical cancer in recessive model (TT vs. CT+CC, OR = 1.23, 95% CI = 1.02-1.49). On subgroup analysis by ethnicity, similarly significant differences in T vs. C, TT vs. CC, and recessive model were found in Asians.

Conclusion: The present meta-analysis suggested that MTHFR C677T polymorphism were to substantially contribute to invasive cervical cancer in recessive model.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Neoplasm Invasiveness
  • Polymorphism, Single Nucleotide*
  • Risk
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology


  • Methylenetetrahydrofolate Reductase (NADPH2)

Grant support

This study was supported by the Chinese National Natural Science Foundation (No. 81071428, 81070505). The authors have declared that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.