Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis

被引:72
作者
Falleti, Edmondo [2 ]
Bitetto, Davide [1 ]
Fabris, Carlo [1 ]
Cussigh, Annarosa [2 ]
Fontanini, Elisabetta [2 ]
Fornasiere, Ezio [1 ]
Fumolo, Elisa [1 ]
Bignulin, Sara [1 ]
Cmet, Sara [2 ]
Minisini, Rosalba [3 ]
Pirisi, Mario [3 ]
Toniutto, Pierluigi [1 ]
机构
[1] Univ Udine, Med Liver Transplant Unit, Dept Med Sci Clin & Expt, I-33100 Udine, Italy
[2] Univ Udine, Lab Med, I-33100 Udine, Italy
[3] Univ Piemonte Orientale, Dept Clin & Expt Med, I-28100 Novara, Italy
关键词
Alcohol; Hepatocellular carcinoma; Liver cirrhosis; Vitamin D receptor polymorphisms; PRIMARY BILIARY-CIRRHOSIS; PROSTATE-CANCER; CUTANEOUS MELANOMA; VDR GENE; ASSOCIATION; RISK; EPIDEMIOLOGY; METAANALYSIS; METABOLISM; HAPLOTYPE;
D O I
10.3748/wjg.v16.i24.3016
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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: Fold 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 Fold F/F = 69, F/f = 73, f/f = 18 and F/F= 36, F/f = 36, f/f = 8; BsmI = 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. (C) 2010 Baishideng. All rights reserved.
引用
收藏
页码:3016 / 3024
页数:9
相关论文
共 37 条
[1]  
[Anonymous], 2007, UPD VIT D POS STAT S
[2]   Haploview: analysis and visualization of LD and haplotype maps [J].
Barrett, JC ;
Fry, B ;
Maller, J ;
Daly, MJ .
BIOINFORMATICS, 2005, 21 (02) :263-265
[3]   Genetic analysis of the vitamin D receptor gene in two epithelial cancers: melanoma and breast cancer case-control studies [J].
Barroso, Eva ;
Fernandez, Lara P. ;
Milne, Roger L. ;
Pita, Guillermo ;
Sendagorta, Elena ;
Floristan, Uxua ;
Feito, Marta ;
Aviles, Jose A. ;
Martin-Gonzalez, Manuel ;
Arias, Jose I. ;
Zamora, Pilar ;
Blanco, Monserrat ;
Lazaro, Pablo ;
Benitez, Javier ;
Ribas, Gloria .
BMC CANCER, 2008, 8 (1)
[4]   Genetic polymorphisms and the progression of liver fibrosis: A critical appraisal [J].
Bataller, R ;
North, KE ;
Brenner, DA .
HEPATOLOGY, 2003, 37 (03) :493-503
[5]   Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT investigators [J].
Beer, Tomasz M. ;
Ryan, Christopher W. ;
Venner, Peter M. ;
Petrylak, Daniel P. ;
Chatta, Gurkamal S. ;
Ruether, J. Dean ;
Redfern, Charles H. ;
Fehrenbacher, Louis ;
Saleh, Mansoor N. ;
Waterhouse, David M. ;
Carducci, Michael A. ;
Vicario, Daniel ;
Dreicer, Robert ;
Higano, Celestia S. ;
Ahmann, Frederick R. ;
Chi, Kim N. ;
Henner, W. David ;
Arroyo, Alan ;
Clow, Fong W. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (06) :669-674
[6]   Nonclassic Actions of Vitamin D [J].
Bikle, Daniel .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (01) :26-34
[7]   Primary liver cancer:: Worldwide incidence and trends [J].
Bosch, FX ;
Ribes, J ;
Díaz, M ;
Cléries, R .
GASTROENTEROLOGY, 2004, 127 (05) :S5-S16
[8]   No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer [J].
Dunning, AM ;
McBride, S ;
Gregory, J ;
Durocher, F ;
Foster, NA ;
Healey, CS ;
Smith, N ;
Pharoah, PDP ;
Luben, RN ;
Easton, DF ;
Ponder, BAJ .
CARCINOGENESIS, 1999, 20 (11) :2131-2135
[9]   Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].
El-Serag, Hashem B. ;
Rudolph, Lenhard .
GASTROENTEROLOGY, 2007, 132 (07) :2557-2576
[10]   Arlequin (version 3.0): An integrated software package for population genetics data analysis [J].
Excoffier, Laurent ;
Laval, Guillaume ;
Schneider, Stefan .
EVOLUTIONARY BIOINFORMATICS, 2005, 1 :47-50