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Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Cancer Causes & Control volume 18, pages 665–675 (2007)Cite this article

Abstract

Objectives

Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective of this study was to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary liver cancer and their possible effect modifications on various environmental risk factors.

Methods

A population-based case–control study was conducted in Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques.

Results

The frequency of MTHFR 677 C/C wild homozygotes genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratios (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06–2.61), 1.21(95% CI: 0.65–2.28) respectively when compared with the MTHFR 677 C/C genotype. Subjects carrying any T genotype have the increased risk of 1.55(95% CI: 1.01–2.40) for development of primary hepatocellular carcinoma. A high degree of linkage disequilibrium was observed between the C677T and A1298C polymorphisms, with the D′ of 0.887 and p < 0.01. The MTHFR 677 any T genotype was suggested to have potentially more than multiplicative interactions with raw water drinking with p-value for adjusted interaction of 0.03.

Conclusion

We observed that the MTHFR 677 C/T genotype was associated with an increased risk of primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might modify the effects of raw water drinking on the risk of primary hepatocellular carcinoma.

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Acknowledgments

This work is supported in part by the International Union Against Cancer (UICC) Technology Transfer fellowship (ICRETT) awarded to Dr. Li-Na Mu and by the Foundation for the Author of National Excellent Doctoral Dissertation of P.R. China, No. 200157, awarded to Dr. Lin Cai. The study was also partially supported by the NIH National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services, Grants ES06718, ES 011667, CA77954, CA09142, CA16042, CA42710, and AT00151, as well as the Alper Research Program of Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center and UCLA Center for Occupational and Environmental Health.

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Affiliations

  1. Department of Epidemiology, Fudan University School of Public Health, Shanghai, China

    Li-Na Mu, Qing-Wu Jiang, Guo-Rong Wei, Chuan-Wei Chen & Shun-Zhang Yu

  2. Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, 90095, USA

    Wei Cao, Zuo-Feng Zhang, Nai-Chieh You & Binh Yang Goldstein

  3. Department of Epidemiology, Fujian Medical University, Fuzhou, Fujian, China

    Lin Cai

  4. UCLA Center for Human Nutrition, School of Medicine, Los Angeles, CA, 90095, USA

    Qing-Yi Lu

  5. Taixing Center of Disease Control & Prevention, Taixing, Jiangsu, China

    Xue-Fu Zhou, Bao-Guo Ding & Jun Chang

  6. Department of Epidemiology and Public Health, School of Medicine, Yale University, 60 College Street, LEPH 400, New Haven, CT, 06520-8034, USA

    Li-Na Mu

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  1. Li-Na Mu
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  2. Wei Cao
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Correspondence to Li-Na Mu.

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Mu, LN., Cao, W., Zhang, ZF. et al. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population. Cancer Causes Control 18, 665–675 (2007). https://doi.org/10.1007/s10552-007-9012-x

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Keywords

  • MTHFR (5, 10-methylenetetralydrofolate reductase)
  • Genetic polymorphism
  • Primary liver cancer
  • Case–control study
  • Effect modification