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Genetic variations in the one-carbon metabolism pathway genes and susceptibility to hepatocellular carcinoma risk: a case–control study

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Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common cause of cancer mortality worldwide. However, the exact molecular mechanism of HCC remains uncertain. Many enzymes are involved in one-carbon metabolism (OCM), and single nucleotide polymorphisms (SNPs) in the corresponding genes may play a role in liver carcinogenesis. In this study, we enrolled 1500 HCC patients and 1500 cancer-free controls, which were frequency-matched by age, gender, and HBV infection status. Then eight SNPs from seven OCM genes (MTHFR, MTR, MTRR, FTHFD, GART, SHMT, and CBS) were evaluated. Results showed that six SNPs (MTHFR rs1801133, MTRR rs2287780, MTRR rs10380, FTHFD rs1127717, GART rs8971, and SHMT rs1979277) were significantly associated with HCC risk in Chinese population, with P values range from 2.26 × 10−4 to 0.035). The most significant association was detected for GART rs8971. Compared with individuals with the TT genotype, the age- and sex-adjusted odds ratio (OR) for developing HCC was 1.44 (95 % confidence interval (CI): 1.03–2.02) among those with the CC genotype and 1.30 (95 % CI: 1.10–1.53) for those with CT genotype. Under the log-additive model, each additional copy of minor allele C was associated with a 1.28-fold increased risk of HCC (OR = 1.28, 95 % CI: 1.12–1.45). These findings indicated that genetic variants in OCM genes might contribute to HCC susceptibility.

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Acknowledgments

We thank all the staffs who were involved in the subject recruitment, telephone interviews, sample preparation, and laboratory assays for their hard works.

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Authors and Affiliations

  1. China Medical University, Shenyang, China

    Heng Zhang & Chunhe Liu

  2. Department of Pathology, Basic Science College, China Medical University, North Erma Road 92, Heping district, 110001, Shenyang, China

    Yu-chen Han, Haiyan Zhang, Yinan Ma & Xiaofang Liu

  3. Hepatobiliary Pancreatic Surgery, Tumor Hospital of Liaoning Province, Shenyang, China

    Zuohong Ma

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  1. Heng Zhang
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  2. Chunhe Liu
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  3. Yu-chen Han
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  4. Zuohong Ma
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  7. Xiaofang Liu
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Correspondence to Yu-chen Han.

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Zhang, H., Liu, C., Han, Yc. et al. Genetic variations in the one-carbon metabolism pathway genes and susceptibility to hepatocellular carcinoma risk: a case–control study. Tumor Biol. 36, 997–1002 (2015). https://doi.org/10.1007/s13277-014-2725-z

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  • DOI: https://doi.org/10.1007/s13277-014-2725-z

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