Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08-2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3'-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33-3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07-3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.
MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals / B. Donati, P. Dongiovanni, S. Romeo, M. Meroni, M. Mccain, L. Miele, S. Petta, S. Maier, C. Rosso, L. De Luca, E. Vanni, S. Grimaudo, R. Romagnoli, F. Colli, F. Ferri, R.M. Mancina, P. Iruzubieta, A. Craxi, A.L. Fracanzani, A. Grieco, S.G. Corradini, A. Aghemo, M. Colombo, G. Soardo, E. Bugianesi, H. Reeves, Q.M. Anstee, S. Fargion, L. Valenti. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017 Jul 03).
|Titolo:||MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||3-lug-2017|
|Centro di ricerca:||Centro per lo studio e la cura delle malattie metaboliche del fegato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41598-017-04991-0|
|Appare nelle tipologie:||01 - Articolo su periodico|