TY  - JOUR
A1  - Lange, Christian
A1  - Miki, Daiki
A1  - Ochi, Hidenori
A1  - Nischalke, Hans-Dieter
A1  - Bojunga, Jörg
A1  - Bibert, Stéphanie
A1  - Morikawa, Kenichi
A1  - Gouttenoire, Jérôme
A1  - Cerny, Andreas
A1  - Dufour, Jean-François
A1  - Gorgievski-Hrisoho, Meri
A1  - Heim, Markus H.
A1  - Malinverni, Raffaele
A1  - Müllhaupt, Beat
A1  - Negro, Francesco
A1  - Semela, David
A1  - Kutalik, Zoltán
A1  - Müller, Tobias
A1  - Spengler, Ulrich
A1  - Berg, Thomas
A1  - Chayama, Kazuaki
A1  - Bochud, Pierre-Yves
A1  - Moradpour, Darius
T1  - Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development
T2  - PLoS One
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29889
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-298896
SN  - 1932-6203
N1  - 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.
VL  - 8
IS  - (5):e64053
SP  - 1
EP  - 7
PB  - PLoS
CY  - Lawrence, Kan.
ER  -