Genetic Analyses Reveal a Role for Vitamin D Insufficiency in HCV-Associated Hepatocellular Carcinoma Development.

Détails

Ressource 1Télécharger: BIB_2C5A41A5E2DE.P001.pdf (249.30 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_2C5A41A5E2DE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genetic Analyses Reveal a Role for Vitamin D Insufficiency in HCV-Associated Hepatocellular Carcinoma Development.
Périodique
Plos One
Auteur(s)
Lange C.M., Miki D., Ochi H., Nischalke H.D., Bojunga J., Bibert S., Morikawa K., Gouttenoire J., Cerny A., Dufour J.F., Gorgievski-Hrisoho M., Heim M.H., Malinverni R., Müllhaupt B., Negro F., Semela D., Kutalik Z., Müller T., Spengler U., Berg T., Chayama K., Moradpour D., Bochud P.Y.
Collaborateur(s)
Hiroshima Liver Study Group, Swiss Hepatitis C Cohort Study Group
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
8
Numéro
5
Pages
e64053
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
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). METHODOLOGYPRINCIPAL 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. CONCLUSIONSSIGNIFICANCE: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/06/2013 11:49
Dernière modification de la notice
20/08/2019 14:11
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