Brief Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Jun 28, 2010; 16(24): 3016-3024
Published online Jun 28, 2010. doi: 10.3748/wjg.v16.i24.3016
Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis
Edmondo Falleti, Davide Bitetto, Carlo Fabris, Annarosa Cussigh, Elisabetta Fontanini, Ezio Fornasiere, Elisa Fumolo, Sara Bignulin, Sara Cmet, Rosalba Minisini, Mario Pirisi, Pierluigi Toniutto
Edmondo Falleti, Annarosa Cussigh, Elisabetta Fontanini, Sara Cmet, Laboratory Medicine, University of Udine, 33100 Udine, Italy
Davide Bitetto, Carlo Fabris, Ezio Fornasiere, Elisa Fumolo, Sara Bignulin, Pierluigi Toniutto, Department of Medical Sciences Clinical and Experimental, Medical Liver Transplant Unit, University of Udine, 33100 Udine, Italy
Rosalba Minisini, Mario Pirisi, Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, 28100 Novara, Italy
Author contributions: Falleti E designed the research and contributed to writing the paper; Cussigh A, Fontanini E, Cmet S and Minisini R performed all the laboratory tests; Bitetto D, Fornasiere E, Fumolo E and Bignulin S performed the clinical evaluation and follow-up of the patients; Fabris C performed the statistical analysis of the data and contributed to writing the paper; Pirisi M and Toniutto P contributed to writing and revising the paper.
Supported by Grants from the Ricerca Sanitaria Finalizzata Program, Regione Piemonte, Italy
Correspondence to: Pierluigi Toniutto, MD, Department of Medical Sciences Clinical and Experimental, Medical Liver Transplant Unit, University of Udine, Piazzale S. M. della Misericordia 1, 33100 Udine, Italy.
Telephone: +39-432-559802 Fax: +39-432-42097
Received: January 8, 2010
Revised: February 10, 2010
Accepted: February 17, 2010
Published online: June 28, 2010

AIM: To assess the relationship between vitamin D receptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC).

METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucleotide gene polymorphisms of the VDR were investigated by polymerase chain reaction and restriction fragment length polymorphism: FokI C>T (F/f), BsmI A>G (B/b), ApaI T>G (A/a) and TaqI T>C (T/t) (BAT).

RESULTS: The frequencies of genotypes in patients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for ApaI A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotype of BsmI and the T/T genotype of TaqI was significantly associated with HCC (45/160 vs 33/80, P < 0.05 and 44/160 vs 32/80, P < 0.05, respectively). The absence of the A-T-C protective allele of BAT was significantly associated with the presence of HCC (46/80 vs 68/160, P < 0.05). A strong association was observed between carriage of the BAT A-T-C and G-T-T haplotypes and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, P < 0.002, respectively).

CONCLUSION: VDR genetic polymorphisms are significantly associated with the occurrence of HCC in patients with liver cirrhosis. This relationship is more specific for patients with an alcoholic etiology.

Keywords: Alcohol, Hepatocellular carcinoma, Liver cirrhosis, Vitamin D receptor polymorphisms