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

Nischalke, Hans Dieter; Lutz, Philipp; Krämer, Benjamin; Söhne, Jennifer; Müller, Tobias; Rosendahl, Jonas; Fischer, Janett; Berg, Thomas; Hittatiya, Kanishka; Fischer, Hans-Peter; Soyka, Michael; Semmo, Nasser; Nattermann, Jacob; Sauerbruch, Tilman; Strassburg, Christian P.; Stickel, Felix; Spengler, Ulrich (2014). A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease. Journal of hepatology, 61(5), pp. 1073-1079. Elsevier 10.1016/j.jhep.2014.06.006

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy

UniBE Contributor:

Soyka, Michael; Semmo, Nasser and Stickel, Felix

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0168-8278

Publisher:

Elsevier

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

20 Mar 2015 13:35

Last Modified:

06 Nov 2015 09:48

Publisher DOI:

10.1016/j.jhep.2014.06.006

PubMed ID:

24946282

Uncontrolled Keywords:

Alcohol, HCC, Liver cirrhosis, NCAN, Neurocan, Polymorphism, SNP, rs2228603

BORIS DOI:

10.7892/boris.65354

URI:

https://boris.unibe.ch/id/eprint/65354

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