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NCAN polymorphism associated with HCC, alcoholic liver disease

The neurocan rs2228603 polymorphism is associated with alcoholic liver disease and hepatocellular carcinoma, according to study results.

Hans Dieter Nischalke, MSc, department of internal medicine, University of Bonn, Germany, and colleagues analyzed data from 356 patients with alcoholic liver cirrhosis, 126 with alcoholic hepatocellular carcinoma (HCC), 382 with alcohol abuse without liver damage, 171 with hepatitis C virus (HCV) associated with HCC and 362 healthy controls. Researchers searched for the neurocan (NCAN) rs2228603 genotype, a T allele, to determine if it was more prevalent in patients with HCC. A validation cohort of 229 patients with alcoholic cirrhosis, 83 also had HCC, was included.

Hans Dieter Nischalke

Patients with HCC due to alcoholic liver disease (ALD) had a higher level of the NCAN rs2228603 gene (15.1%) compared with patients with cirrhosis without HCC (9.3%), HCV-associated HCC (9.1%), alcoholic controls (7.2%) and healthy controls (7.9%). In addition, patients with alcoholic cirrhosis and HCC in the validation cohort also had higher levels of rs2228603 (15.7%) compared with the patients with alcoholic cirrhosis alone (6.8%) (OR=2.53; 95% CI, 1.36-4.68).

Researchers learned that a higher frequency of HCC T allele carriers did not relate to increased survival rate, but was associated with an increased probability for HCC. Univariate analysis revealed that age, male sex, BMI, NCAN rs2228603 and the PNPLA3 148M variant were independent risk factors for alcohol-related HCC. NCAN mRNA steady state expression levels were at their highest in patients with ALD-induced HCC. Patients with alcoholic cirrhosis had higher mRNA levels compared with HCV-induced liver cirrhosis.

“The NCAN rs2228603 polymorphism is a risk factor for HCC in ALD, but not in HCV infection,” Nischalke told Healio.com/Hepatology. “NCAN is not only expressed in neuronal tissue, but also in the liver, and our findings indicate a so far unknown involvement of NCAN in alcohol-mediated hepatocarcinogenesis.”

Disclosure: The researchers report no relevant financial disclosures.