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Sci Rep. 2017 Jul 3;7(1):4492. doi: 10.1038/s41598-017-04991-0.

MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.

Author information

1
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy.
2
Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy.
3
Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Department of Cardiology, University of Gothenburg, Gothenburg, Sweden.
4
Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy.
5
Northern Institute of Cancer Research, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK.
6
Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
7
Internal Medicine, Policlinico Gemelli, Roma, Italy.
8
Department of Gastroenterology, Università di Palermo, Palermo, Italy.
9
Internal Medicine and Liver Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
10
Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy.
11
General Surgery and Liver Transplantation Center, Department of Surgical Sciences, University of Turin, Turin, Italy.
12
Department of Clinical Medicine, Gastroenterology division, Sapienza University, Rome, Italy.
13
Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK.
14
Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy.
15
Hepatology, Humanitas Clinical and Research Center, Rozzano, Italy.
16
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy. luca.valenti@unimi.it.
17
Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy. luca.valenti@unimi.it.

Abstract

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.

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