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The MTHFR polymorphism affect the susceptibility of HCC and the prognosis of HCC liver transplantation

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Abstract

Background

Methylenetetrahyfrofolate reductase (MTHFR) is the key enzyme for one carbon and folate metabolism. Previous studies have drawn different conclusions about the relationship between the mutation of MTHFR and hepatocellular carcinoma (HCC) occurrence. MTHFR polymorphisms' influence on liver transplantation for HCC recurrence has yet not been reported. Aim of this study was to clarify the impact of MTHFR polymorphism on hepatocarcinogenesis and the prognosis of liver transplant recipient with HCC.

Methods

This study enrolled 244 HCC patients and 487 healthy individuals in Chinese Han population to analyze the influence of MTHFR polymorphism on HCC susceptibility first. Furthermore, this research choose another 100 donors’ and 104 recipients’ specimens to detect the association between polymorphism of MTHFR and post-transplant HCC recurrence.

Result

rs1801131 polymorphism A to C was associated with the occurrence of HCC in Chinese Han population (p < 0.05), especially in age exceeding 50 years (p < 0.01). No association was observed with rs1801133 polymorphism and HCC occurrence. The mean tumor-free survival for recipients with donor liver graft rs1801133 C to T variants was shorter than CC type (12.63 ± 3.84 vs 22.43 ± 4.74 months, p < 0.05). Multivariate analysis revealed that Donor rs1801133 and Hangzhou criteria were two independent prognostic factors for tumor-free survival (p < 0.05). Neither donor rs1801131 polymorphism nor recipients’ MTHFR polymorphisms was associated with HCC recurrence.

Conclusion

This study demonstrated that MTHFR polymorphism was associated with HCC occurrence and post-transplant HCC recurrence. rs1801131 mutation A to C is a valuable molecular biomarker for predicting HCC occurrence in Chinese Han population. Donor MTHFR rs1801133 C to T polymorphism could present as a promising prognostic biomarkers for HCC recurrence in liver transplant recipients.

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Abbreviations

LT:

Liver transplantation

HCC:

Hepatocellular carcinoma

MTHFR:

Methylenetetrahyfrofolate reductase

SAM:

S-adenosylmethionine

HBV:

Hepatitis B virus

AFP:

Alpha fetoprotein

SNP:

Single nucleotide polymorphism

OS:

Overall survival

TFS:

Tumor-free survival

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Acknowledgements

This work was supported by the National High Technology Research and Development Program of China (863 Program 2012AA020204), the National Natural Science Foundation of China (81570589), National Natural Science Foundation of China (81470892), Major science and technology projects of Zhejiang province (2014C13G2010021), and Shenzhen Sanming Plan.

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Authors and Affiliations

  1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    C. Wang, H. Xie, D. Lu, Q. Ling, P. Jin, R. Zhuang, X. Xu & S. Zheng

  2. Shenzhen Key Laboratory of Hepatobiliary Disease, Shenzhen Third People’s Hospital, Shenzhen, China

    H. Li

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  1. C. Wang
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  2. H. Xie
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  3. D. Lu
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  4. Q. Ling
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Contributions

Chao Wang and Haiyang Xie participated in the design of the study and drafted the manuscript. Qi Ling and Hongchun Li participated in the specimen collection. Chao Wang and Di Lu carried out the molecular genetic studies, Pingbo Jin, Runzhou Zhuang collected clinical data and performed the statistical analysis. Xiao Xu and Shusen Zheng conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to S. Zheng.

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Conflict of interest

All of the authors indicate that we have no potential conflict of interest relevant to this article.

Ethics statement

Informed consent was obtained from each case and control. Every transplant was approved by the Institutional Review Board, First Affiliated Hospital, Zhejiang University School of Medicine, under the guidelines of the Ethics Committee of the hospital, and the Declaration of Helsinki.

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Wang, C., Xie, H., Lu, D. et al. The MTHFR polymorphism affect the susceptibility of HCC and the prognosis of HCC liver transplantation. Clin Transl Oncol 20, 448–456 (2018). https://doi.org/10.1007/s12094-017-1729-8

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  • DOI: https://doi.org/10.1007/s12094-017-1729-8

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