Donor one‑carbon metabolism gene single nucleotide polymorphisms predict the susceptibility of cancer recurrence after liver transplantation

Gene. 2019 Mar 20;689:97-101. doi: 10.1016/j.gene.2018.11.035. Epub 2018 Dec 7.

Abstract

Background: Many enzymes involved in one‑carbon metabolism (OCM) are considered to have important roles in carcinogenesis, especially in hepatocellular carcinoma (HCC). However, the influence of polymorphisms in OCM genes on recurrence in HCC patients with liver transplantation has yet not been reported. The aim of this study was to explore the impact of donor liver graft OCM gene polymorphism on the prognosis of liver transplant recipients with HCC.

Methods: This study enrolled 100 liver transplantation patients from a Chinese Han population to detect the association between donor OCM genes polymorphisms and post-transplant HCC recurrence. Nine SNPs from seven OCM genes (MTHFD1, MTR, MTRR, DHFR, ALDH1L1, SHMT1, and CBS) were evaluated by Chi-square test and Kaplan-Meier survival analysis.

Result: None of the nine SNPs were significantly associated with cancer recurrence after liver transplantation. However, tumor-free survival for recipients with the AA genotype of rs1801394 polymorphism was significantly shorter than patients with AG/GG genotype (1097 ± 155 vs. 1657 ± 173 days, P < 0.05) among patients with alpha-fetoprotein < 400 ng/ml. Kaplan-Meier survival curves showed that recipients with donor rs1127717 homozygous TT had a significantly longer tumor-free survival and overall survival than heterozygous CT/CC recipients (tumor-free survival 1395 ± 128 vs. 671 ± 233 days, P < 0.05; overall survival 1540 ± 114 vs. 925 ± 242 days, P < 0.05) in the patient subgroup with well or moderately differentiated HCC.

Conclusion: This is the first genetic study to examine the relation between donor liver graft OCM gene polymorphisms and the risk of HCC recurrence after liver transplantation. Our findings support the hypothesis that polymorphisms of donor genes related to OCM play important roles in post-transplant HCC recurrence. Furthermore, donor rs1801394 and rs1127717 polymorphism may serve as promising prognostic biomarkers for HCC recurrence in liver transplant recipients.

Keywords: Cancer recurrence; Hepatocellular carcinoma; Liver transplantation; One‑carbon metabolism; Single nucleotide polymorphism.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carbon / metabolism*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Liver Transplantation*
  • Male
  • Metabolic Networks and Pathways / genetics
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Tissue Donors*

Substances

  • Biomarkers, Tumor
  • Carbon