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

doi:10.1016/j.jhep.2014.06.006

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

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	1073-1079
Number of pages	7
Journal	Journal of Hepatology
Volume	61
Issue number	5
Early online date	16 Jun 2014
DOIs	https://doi.org/10.1016/j.jhep.2014.06.006
Publication status	Published - 1 Nov 2014

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Nischalke, H. D., Lutz, P., Krämer, B., Söhne, J., Müller, T., Rosendahl, J., Fischer, J., Berg, T., Hittatiya, K., Fischer, H-P., Soyka, M., Semmo, N., Nattermann, J., Sauerbruch, T., Strassburg, C. P., Stickel, F., & Spengler, U. (2014). A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease. Journal of Hepatology, 61(5), 1073-1079. Advance online publication. https://doi.org/10.1016/j.jhep.2014.06.006

@article{da107e7c90d245a48837920994fae744,

title = "A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease",

abstract = "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.",

keywords = "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",

author = "Nischalke, {Hans Dieter} and Philipp Lutz and Benjamin Kr{\"a}mer and Jennifer S{\"o}hne and Tobias M{\"u}ller and Jonas Rosendahl and Janett Fischer and Thomas Berg and Kanishka Hittatiya and Hans-Peter Fischer and Michael Soyka and Nasser Semmo and Jacob Nattermann and Tilman Sauerbruch and Strassburg, {Christian P} and Felix Stickel and Ulrich Spengler",

year = "2014",

month = nov,

day = "1",

doi = "10.1016/j.jhep.2014.06.006",

language = "English",

volume = "61",

pages = "1073--1079",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "5",

}

Nischalke, HD, Lutz, P, Krämer, B, Söhne, J, Müller, T, Rosendahl, J, Fischer, J, Berg, T, Hittatiya, K, Fischer, H-P, Soyka, M, Semmo, N, Nattermann, J, Sauerbruch, T, Strassburg, CP, Stickel, F & Spengler, U 2014, 'A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease', Journal of Hepatology, vol. 61, no. 5, pp. 1073-1079. https://doi.org/10.1016/j.jhep.2014.06.006

TY - JOUR

T1 - A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease

AU - Nischalke, Hans Dieter

AU - Lutz, Philipp

AU - Krämer, Benjamin

AU - Söhne, Jennifer

AU - Müller, Tobias

AU - Rosendahl, Jonas

AU - Fischer, Janett

AU - Berg, Thomas

AU - Hittatiya, Kanishka

AU - Fischer, Hans-Peter

AU - Soyka, Michael

AU - Semmo, Nasser

AU - Nattermann, Jacob

AU - Sauerbruch, Tilman

AU - Strassburg, Christian P

AU - Stickel, Felix

AU - Spengler, Ulrich

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alcoholism

KW - Carcinoma, Hepatocellular

KW - Case-Control Studies

KW - Cell Line

KW - Chondroitin Sulfate Proteoglycans

KW - Cohort Studies

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Hep G2 Cells

KW - Hepatitis C, Chronic

KW - Hepatocytes

KW - Humans

KW - Lectins, C-Type

KW - Liver Cirrhosis, Alcoholic

KW - Liver Diseases, Alcoholic

KW - Liver Neoplasms

KW - Male

KW - Middle Aged

KW - Nerve Tissue Proteins

KW - Polymorphism, Single Nucleotide

KW - RNA, Messenger

KW - Risk Factors

KW - Young Adult

KW - NCAN

KW - HCC

KW - Liver cirrhosis

KW - Alcohol

KW - Neurocan

KW - rs2228603

KW - Polymorphism

KW - SNP

U2 - 10.1016/j.jhep.2014.06.006

DO - 10.1016/j.jhep.2014.06.006

M3 - Article

C2 - 24946282

SN - 0168-8278

VL - 61

SP - 1073

EP - 1079

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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