Christian 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, Zoltán Kutalik, Tobias Müller, Ulrich Spengler, Thomas Berg, Kazuaki Chayama, Pierre-Yves Bochud, Darius Moradpour
- Background: 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).
Methodology/Principal Findings: 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.
Conclusions/Significance: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.
MetadatenAuthor: | Christian LangeGND, Daiki Miki, Hidenori Ochi, Hans-Dieter Nischalke, Jörg BojungaGND, 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, Zoltán KutalikORCiDGND, Tobias MüllerORCiDGND, Ulrich SpenglerORCiDGND, Thomas BergORCiDGND, Kazuaki Chayama, Pierre-Yves Bochud, Darius MoradpourORCiDGND |
---|
URN: | urn:nbn:de:hebis:30:3-298896 |
---|
DOI: | https://doi.org/10.1371/journal.pone.0064053 |
---|
ISSN: | 1932-6203 |
---|
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/23734184 |
---|
Parent Title (English): | PLoS One |
---|
Publisher: | PLoS |
---|
Place of publication: | Lawrence, Kan. |
---|
Document Type: | Article |
---|
Language: | English |
---|
Date of Publication (online): | 2013/05/29 |
---|
Date of first Publication: | 2013/05/29 |
---|
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
---|
Contributing Corporation: | the Hiroshima Liver Study Group ; the Swiss Hepatitis C Cohort Study Group |
---|
Release Date: | 2013/05/31 |
---|
Volume: | 8 |
---|
Issue: | (5):e64053 |
---|
Page Number: | 7 |
---|
First Page: | 1 |
---|
Last Page: | 7 |
---|
Note: | Copyright: © 2013 Lange et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
---|
HeBIS-PPN: | 341088579 |
---|
Institutes: | Medizin / Medizin |
---|
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
---|
Sammlungen: | Universitätspublikationen |
---|
Licence (German): | Creative Commons - Namensnennung 3.0 |
---|