PLoS ONE (Jan 2013)

Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.

  • Christian M Lange,
  • Daiki Miki,
  • Hidenori Ochi,
  • Hans-Dieter Nischalke,
  • Jörg Bojunga,
  • Stéphanie Bibert,
  • Kenichi Morikawa,
  • Jérôme Gouttenoire,
  • Andreas Cerny,
  • Jean-François Dufour,
  • Meri Gorgievski-Hrisoho,
  • Markus H Heim,
  • Raffaele Malinverni,
  • Beat Müllhaupt,
  • Francesco Negro,
  • David Semela,
  • Zoltan Kutalik,
  • Tobias Müller,
  • Ulrich Spengler,
  • Thomas Berg,
  • Kazuaki Chayama,
  • Darius Moradpour,
  • Pierre-Yves Bochud,
  • Hiroshima Liver Study Group,
  • Swiss Hepatitis C Cohort Study Group

DOI
https://doi.org/10.1371/journal.pone.0064053
Journal volume & issue
Vol. 8, no. 5
p. e64053

Abstract

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Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99-1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12-2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13-1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP) or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis.Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.