MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals
- Autori: Donati, B.; Dongiovanni, P.; Romeo, S.; Meroni, M.; Mccain, M.; Miele, L.; Petta, S.; Maier, S.; Rosso, C.; De Luca, L.; Vanni, E.; Grimaudo, S.; Romagnoli, R.; Colli, F.; Ferri, F.; Mancina, R.; Iruzubieta, P.; Craxi, A.; Fracanzani, A.; Grieco, A.; Corradini, S.; Aghemo, A.; Colombo, M.; Soardo, G.; Bugianesi, E.; Reeves, H.; Anstee, Q.; Fargion, S.; Valenti, L.
- Anno di pubblicazione: 2017
- Tipologia: Articolo in rivista (Articolo in rivista)
- OA Link: http://hdl.handle.net/10447/247585
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.