A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease

Hans Dieter Nischalke, Philipp Lutz, Benjamin Krämer, Jennifer Söhne, Tobias Müller, Jonas Rosendahl, Janett Fischer, Thomas Berg, Kanishka Hittatiya, Hans-Peter Fischer, Michael Soyka, Nasser Semmo, Jacob Nattermann, Tilman Sauerbruch, Christian P Strassburg, Felix Stickel, Ulrich Spengler

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


BACKGROUND & AIMS: The genetic background of alcoholic liver diseases and their complications are increasingly recognized. A common polymorphism in the neurocan (NCAN) gene, which is known to be expressed in neuronal tissue, has been identified as a risk factor for non-alcoholic fatty liver disease (NAFLD). We investigated if this polymorphism may also be related to alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC).

METHODS: We analysed the distribution of the NCAN rs2228603 genotypes in 356 patients with alcoholic liver cirrhosis, 126 patients with alcoholic HCC, 382 persons with alcohol abuse without liver damage, 362 healthy controls and in 171 patients with hepatitis C virus (HCV) associated HCC. Furthermore, a validation cohort of 229 patients with alcoholic cirrhosis (83 with HCC) was analysed. The genotypes were determined by LightSNiP assays. The expression of NCAN was studied by RT-PCR and immunofluorescence microscopy.

RESULTS: The frequency of the NCAN rs2228603 T allele was significantly increased in patients with HCC due to ALD (15.1%) compared to alcoholic cirrhosis without HCC (9.3%), alcoholic controls (7.2%), healthy controls (7.9%), and HCV associated HCC (9.1%). This finding was confirmed in the validation cohort (15.7% vs. 6.8%, OR=2.53; 95%CI: 1.36-4.68; p=0.0025) and by multivariate analysis (OR=1.840; 95%CI: 1.22-2.78; p=0.004 for carriage of the rs2228603 T allele). In addition, we identified and localised NCAN expression in human liver.

CONCLUSIONS: NCAN is not only expressed in neuronal tissue, but also in the liver. Its rs2228603 polymorphism is a risk factor for HCC in ALD, but not in HCV infection.

Original languageEnglish
Pages (from-to)1073-1079
Number of pages7
JournalJournal of Hepatology
Issue number5
Early online date16 Jun 2014
Publication statusPublished - 1 Nov 2014


  • Adult
  • Aged
  • Aged, 80 and over
  • Alcoholism
  • Carcinoma, Hepatocellular
  • Case-Control Studies
  • Cell Line
  • Chondroitin Sulfate Proteoglycans
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Hep G2 Cells
  • Hepatitis C, Chronic
  • Hepatocytes
  • Humans
  • Lectins, C-Type
  • Liver Cirrhosis, Alcoholic
  • Liver Diseases, Alcoholic
  • Liver Neoplasms
  • Male
  • Middle Aged
  • Nerve Tissue Proteins
  • Polymorphism, Single Nucleotide
  • RNA, Messenger
  • Risk Factors
  • Young Adult
  • NCAN
  • HCC
  • Liver cirrhosis
  • Alcohol
  • Neurocan
  • rs2228603
  • Polymorphism
  • SNP


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