Dataset Information

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

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-? 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.

SUBMITTER: Lange CM

PROVIDER: S-EPMC3667029 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Lange Christian M CM Miki Daiki D Ochi Hidenori H Nischalke Hans-Dieter HD Bojunga Jörg J Bibert Stéphanie S Morikawa Kenichi K Gouttenoire Jérôme J Cerny Andreas A Dufour Jean-François JF Gorgievski-Hrisoho Meri M Heim Markus H MH Malinverni Raffaele R Müllhaupt Beat B Negro Francesco F Semela David D Kutalik Zoltan Z Müller Tobias T Spengler Ulrich U Berg Thomas T Chayama Kazuaki K Moradpour Darius D Bochud Pierre-Yves PY

PloS one 20130529 5

<h4>Background</h4>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).<h4>Methodology/principal findings</h4>Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3 ...[more]

PMID: 23734184

Similar Datasets

Project description:Hepatitis C virus (HCV) is a major cause of hepatitis and hepatocellular carcinoma (HCC) world-wide. Most HCV patients have relatively stable disease, but approximately 25% have progressive disease that often terminates in liver failure or HCC. HCV is highly variable genetically, with seven genotypes and multiple subtypes per genotype. This variation affects HCV's sensitivity to antiviral therapy and has been implicated to contribute to differences in disease. We sequenced the complete viral coding capacity for 107 HCV genotype 1 isolates to determine whether genetic variation between independent HCV isolates is associated with the rate of disease progression or development of HCC. Consensus sequences were determined by sequencing RT-PCR products from serum or plasma. Positions of amino acid conservation, amino acid diversity patterns, selection pressures, and genome-wide patterns of amino acid covariance were assessed in context of the clinical phenotypes. A few positions were found where the amino acid distributions or degree of positive selection differed between in the HCC and cirrhotic sequences. All other assessments of viral genetic variation and HCC failed to yield significant associations. Sequences from patients with slow disease progression were under a greater degree of positive selection than sequences from rapid progressors, but all other analyses comparing HCV from rapid and slow disease progressors were statistically insignificant. The failure to observe distinct sequence differences associated with disease progression or HCC employing methods that previously revealed strong associations with the outcome of interferon α-based therapy implies that variable ability of HCV to modulate interferon responses is not a dominant cause for differential pathology among HCV patients. This lack of significant associations also implies that host and/or environmental factors are the major causes of differential disease presentation in HCV patients.

Dataset Information

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

Background

Methodology/principal findings

Conclusions/significance

Publications

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

Similar Datasets

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