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The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case–control studies

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Abstract

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to cancer. As the most extensively studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer susceptibility but the results were inconsistent. The authors performed a meta-analysis including 134 studies (46,207 cases and 69,160 controls) to address the issue. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of cancer was associated with the MTHFR C677T polymorphism in T-allele versus C-allele comparison (OR = 1.06, 95 % CI 1.02–1.11, P heterogeneity  < 0.001), homozygote model (OR = 1.08, 95 % CI 1.01–1.17, P heterogeneity  < 0.001) and dominant model (OR = 1.05, 95 % CI 1.00–1.10, P heterogeneity  < 0.001). In the stratified analyses, significantly increased cancer risks were indicated among Asians in all genetic models except for heterozygote model. Further analysis revealed that C677T was significantly associated with an increased risk of esophageal and stomach cancer. This meta-analysis supports an association between the MTHFR C677T polymorphism and increased risk of esophageal and stomach cancer, especially among Asians. Additionally, more high-quality studies and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of MTHFR C677T in cancer.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Numbers: 81170612 and 81201571), by the Program for Development of Innovative Research Team in the First Affiliated Hospital of Nanjing Medical University, Provincial Initiative Program for Excellency Disciplines of Jiangsu Province.

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  1. Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Min Tang, Shang-Qian Wang, Bian-Jiang Liu, Qiang Cao, Peng-Chao Li, Yong-Fei Li, Chao Qin & Wei Zhang

  2. Division of Epidemiology, University of Texas Health Science Center, Houston, TX, USA

    Bing-Jie Li

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  1. Min Tang
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Correspondence to Chao Qin or Wei Zhang.

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Min Tang, Shang-Qian Wang and Bian-Jiang Liu have contributed equally to this study.

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Tang, M., Wang, SQ., Liu, BJ. et al. The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case–control studies. Mol Biol Rep 41, 4659–4673 (2014). https://doi.org/10.1007/s11033-014-3337-9

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