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

Publikation

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

Wissenschaftlicher Artikel/Review - 29.05.2013

Lange Christian M, Negro Francesco, Semela David, Kutalik Zoltán, Müller Tobias, Spengler Ulrich, Berg Thomas, Chayama Kazuaki, Moradpour Darius, Bochud Pierre-Yves, Hiroshima Liver Study Group, Mullhaupt Beat, Malinverni Raffaele, Heim Markus H, Miki Daiki, Ochi Hidenori, Nischalke Hans-Dieter, Bojunga Jörg, Bibert Stéphanie, Morikawa Kenichi, Gouttenoire Jérôme, Cerny Andreas, Dufour Jean-François, Gorgievski-Hrisoho Meri, Swiss Hepatitis C Cohort Study Group

Zitation

Lange C, Negro F, Semela D, Kutalik Z, Müller T, Spengler U, Berg T, Chayama K, Moradpour D, Bochud P, Hiroshima Liver Study Group, Mullhaupt B, Malinverni R, Heim M, Miki D, Ochi H, Nischalke H, Bojunga J, Bibert S, Morikawa K, Gouttenoire J, Cerny A, Dufour J, Gorgievski-Hrisoho M, Swiss Hepatitis C Cohort Study Group. Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development. PloS one 2013; 8:e64053.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

PloS one 2013; 8

Veröffentlichungsdatum

29.05.2013

eISSN (Online)

1932-6203

Seiten

e64053

Kurzbeschreibung/Zielsetzung

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.