Vitamin D pathway gene polymorphisms and hepatocellular carcinoma in chronic hepatitis C-affected patients treated with new drugs

Cancer Chemother Pharmacol. 2018 Mar;81(3):615-620. doi: 10.1007/s00280-018-3520-0. Epub 2018 Jan 22.

Abstract

Purpose: Since HCV infection may lead to hepatocellular carcinoma (HCC) and vitamin D (deficiency) is related to cancer, we investigated if SNPs in genes involved in vitamin D pathway could predict HCV-related HCC presence in patients treated with new anti-HCV drugs.

Methods: Patients with chronic hepatitis C and treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1, CYP24A1 and GC genes were assessed through real-time PCR. 258 patients were analyzed.

Results: HCC was present in six patients, all taking sofosbuvir, all males and five/six had cirrhosis. HCV-RNA log levels at baseline were statistically different between patients with and without HCC. VDR FokI T > C SNP resulted associated with HCC: all the CC patients were free from HCC. An association between HCC presence and undetectable HCV-RNA at 1 month of therapy was suggested; cirrhosis was related to HCC. HCC risk factors were age, ribavirin administration, IL28Brs12979860CC and previous treatments; VDR FokICC, sex and insulin resistance were protective factors.

Conclusions: These data highlighted vitamin D pathway gene SNPs and HCC relationship in the Italian population; further studies are required.

Keywords: Hepatocellular carcinoma; Pharmacogenetics; SNP; Sofosbuvir; VDR; Viral hepatitis; Vitamin D.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Neoplasms / complications
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase / genetics

Substances

  • Antiviral Agents
  • Receptors, Calcitriol
  • Vitamin D
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase