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

Lange, C. M. and Miki, D. and Ochi, H. and Nischalke, H. D. and Bojunga, J. and Bibert, S. and Morikawa, K. and Gouttenoire, J. and Cerny, A. and Dufour, J. F. and Gorgievski-Hrisoho, M. and Heim, M. H. and Malinverni, R. and Mullhaupt, B. and Negro, F. and Semela, D. and Kutalik, Z. and Muller, T. and Spengler, U. and Berg, T. and Chayama, K. and Moradpour, D. and Bochud, P. Y.. (2013) Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development. PLoS ONE, Vol. 8, H. 5 , e64053.

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Official URL: http://edoc.unibas.ch/dok/A6338539

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Abstract

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-alpha 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:39
Deposited On:10 Apr 2015 09:14

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