title: 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).
  
  
  RESULTS
  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
  Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.
authors.affiliation: Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. lange_christian1@yahoo.de
authors.forename: Christian M
authors.initials: CM
authors.lastname: Lange
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Nischalke
authors.forename: Jörg
authors.initials: J
authors.lastname: Bojunga
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Kenichi
authors.initials: K
authors.lastname: Morikawa
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gouttenoire
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dufour
authors.forename: Meri
authors.initials: M
authors.lastname: Gorgievski-Hrisoho
authors.forename: Markus H
authors.initials: MH
authors.lastname: Heim
authors.forename: Raffaele
authors.initials: R
authors.lastname: Malinverni
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: David
authors.initials: D
authors.lastname: Semela
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000821:virology; D002648:Child; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D015331:Cohort Studies; D000072467:Cytochrome P450 Family 2; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000235:genetics*; D014809:Vitamin D-Binding Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase