|
HCC |Abstract Library |
|
|
The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors. |
Abstract Details |
|
|
|
|
|
|
|
|
The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis |
|
|
|
|
|
Hepatol Commun. 2022 May;6(5):1213-1226. doi: 10.1002/hep4.1886.Epub 2021 Dec 27.
Hamish Innes 1 2 3, Hans Dieter Nischalke 4, Indra Neil Guha 5, Karl Heinz Weiss 6, Will Irving 5, Daniel Gotthardt 7, Eleanor Barnes 8, Janett Fischer 9, M Azim Ansari 8, Jonas Rosendahl 10, Shang-Kuan Lin 8, Astrid Marot 11 12, Vincent Pedergnana 13, Markus Casper 14, Jennifer Benselin 5, Frank Lammert 14, John McLauchlan 15, Philip L Lutz 4, Victoria Hamill 1 3, Sebastian Mueller 16 17, Joanne R Morling 2 5, Georg Semmler 18 19, Florian Eyer 20, Johann von Felden 21, Alexander Link 22, Arndt Vogel 23, Jens U Marquardt 24, Stefan Sulk 25, Jonel Trebicka 26 27, Luca Valenti 28 29, Christian Datz 19, Thomas Reiberger 18, Clemens Schafmayer 30, Thomas Berg 9, Pierre Deltenre # 11 31 32, Jochen Hampe # 25 33, Felix Stickel # 34, Stephan Buch # 25
|
|
|
|
|
Author information
- 1School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.
- 2Population and Lifespan Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
- 3Public Health Scotland, Glasgow, United Kingdom.
- 4Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany.
- 5National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham University Hospitals National Health Service Trust and the University of Nottingham, Nottingham, United Kingdom.
- 6Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg, Germany.
- 7Department of Internal Medicine IV, Medical University of Heidelberg, Heidelberg, Germany.
- 8Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the Oxford NIHR Biomedical Research Centre, Oxford University, Oxford, United Kingdom.
- 9Division of Hepatology, Department of Medicine II, Laboratory for Clinical and Experimental Hepatology, Leipzig University Medical Center, Leipzig, Germany.
- 10Medical Department 1, University Hospital Halle, Martin-Luther Universität Halle-Wittenberg, Halle, Germany.
- 11Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Lausanne, Switzerland.
- 12Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire, UCLouvain Namur, Université Catholique de Louvain, Yvoir, Belgium.
- 13Laboratoire MIVEGEC, Montpellier, France.
- 14Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
- 15Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- 16Center for Alcohol Research, University of Heidelberg, Heidelberg, Germany.
- 17Medical Department, Salem Medical Center, Heidelberg, Germany.
- 18Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
- 19Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Austria.
- 20Department of Clinical Toxicology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
- 21Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 22Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
- 23Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
- 24Department of Medicine I, University Hospital Schleswig Holstein-Campus Lübeck, Lübeck, Germany.
- 25Medical Department 1, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
- 26Department of Internal Medicine I, Goethe University, Frankfurt, Germany.
- 27European Foundation for Study of Chronic Liver Failure, Barcelona, Spain.
- 28Precision Medicine-Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- 29Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
- 30Department of General, Visceral, Vascular, and Transplant Surgery, Rostock University Medical Center, Rostock, Germany.
- 31Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, University Clinics of Brussels Hospital Erasme, Brussels, Belgium.
- 32Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium.
- 33Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
- 34Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland.
#Contributed equally.
Abstract
The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10-5 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10-6 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.
|
|
|
|
|
|
|
|
|
|
|
|
|