Genetic Analyses Reveal a Role for Vitamin D Insufficiency in HCV-Associated Hepatocellular Carcinoma Development
Open Access
- 29 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e64053
- https://doi.org/10.1371/journal.pone.0064053
Abstract
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.This publication has 20 references indexed in Scilit:
- A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis CPLOS ONE, 2012
- Genetic Variation in IL28B Is Associated With Chronic Hepatitis C and Treatment Failure: A Genome-Wide Association StudyGastroenterology, 2010
- Genome-wide association study of circulating vitamin D levelsHuman Molecular Genetics, 2010
- The Yin and Yang of vitamin D receptor (VDR) signaling in neoplastic progression: Operational networks and tissue-specific growth controlBiochemical Pharmacology, 2010
- Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis CHepatology, 2009
- Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis CJournal of Hepatology, 2009
- Vitamin D DeficiencyThe New England Journal of Medicine, 2007
- Cohort Profile: The Swiss Hepatitis C Cohort Study (SCCS)International Journal of Epidemiology, 2007
- A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinomaBritish Journal of Cancer, 2003
- Serum Vitamin D Metabolites and Their Binding Protein in Patients with Liver CirrhosisJournal of Clinical Endocrinology & Metabolism, 1984