Z Gastroenterol 2022; 60(01): e32
DOI: 10.1055/s-0041-1740755
Abstracts | GASL

Variants APOE (rs429358) and TM6SF2 (rs187429064) modify the risk of hepatocellular carcinoma

Hamish Innes
1   Glasgow Caledonian University, Glasgow, UK
,
HansDieter Nischalke
2   University Hospital, University of Bonn, Germany
,
KarlHeinz Weiss
3   University Hospital Heidelberg, Heidelberg, Germany
,
Daniel Gotthardt
4   Medical University of Heidelberg, Heidelberg, Germany
,
Neil Guha
5   Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
,
Eleanor Barnes
6   Oxford University, Oxford, UK
,
Will Irving
5   Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
,
Janett Fischer
7   Leipzig University Medical Center, Laboratory for Clinical and Experimental Hepatology, Leipzig, Germany
,
Jonas Rosendahl
8   Martin-Luther Universität Halle-Wittenberg, Halle, Germany
,
Markus Casper
9   Saarland University, Homburg, Germany
,
Frank Lammert
10   Saarland University Medical Center, Saarland University, Homburg, Germany
,
PhilipL Lutz
2   University Hospital, University of Bonn, Germany
,
Sebastian Mueller
11   University of Heidelberg and Medical Department, Salem Medical Center , Heidelberg
,
Georg Semmler
12   Medical University of Vienna, Vienna, Austria
,
Florian Eyer
13   Klinikum Rechts der Isar, Technical University of Munich, Germany
,
Johann von Felden
14   University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Alexander Link
15   Otto-von-Guericke University Hospital, Magdeburg, Germany
,
Arndt Vogel
16   Hannover Medical School, Germany
,
JensU Marquardt
17   University Hospital Schleswig Holstein – Campus Lübeck, Lübeck, Germany
,
Stefan Sulk
18   University Hospital Dresden, TU Dresden, Germany
,
Christian Datz
19   General Hospital Oberndorf, Oberndorf, Austria
,
Thomas Reiberger
12   Medical University of Vienna, Vienna, Austria
,
Clemens Schafmayer
20   Rostock University Medical Center, Rostock, Germany
,
Thomas Berg
7   Leipzig University Medical Center, Laboratory for Clinical and Experimental Hepatology, Leipzig, Germany
,
Jochen Hampe
21   University Hospital Dresden, TU Dresden, Dresden, Germany
,
Felix Stickel
22   University Hospital of Zurich, Zurich, Switzerland
,
Stephan Buch
23   Universitätsklinikum Dresden, Dresden, Germany
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    Background & Aims The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in APOE, rs2642438 in MARC1; rs2792751 in GPAM and rs187429064 in TM6SF2, previously associated with progressive alcohol-related and non-alcoholic fatty liver disease are also associated with HCC.

    Patients & Methods Four HCC case-control datasets were constructed, including two mixed etiology datasets (UK Biobank and FinnGen); one HCV cohort (STOPHCV) and one alcohol-related HCC cohort (Dresden HCC). Cases with HCC were compared against cirrhosis controls (i. e. cirrhosis patients without HCC). Adjusted odds ratios (OR) reflecting variant frequency in cases versus controls were calculated using multivariate logistic regression under an additive genetic model. Fixed-effect meta-analysis was used to determine the average effect size across all datasets.

    Results Across four case-control datasets, 2,070 HCC cases, 4,958 cirrhosis controls. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus controls OR: 0.68; 95%CI: 0.58-0.79; P=9.30×10-7). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus controls and exhibited the strongest effect size (OR: 2.61;95%CI:1.97-3.39; P=1.4×10-11). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR:0.99; 95%CI:0.90-1.08; P=0.85), whilst rs2642438:A (MARC1) was less frequent in cases versus controls, but narrowly missed statistical significance (OR: 0.89; 95%CI:0.80-0.98; P=0.02).

    Conclusion This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC, whereas carriage of rs187429064:G in TM6SF2 is associated with an increased HCC risk. No association with HCC was found for GPAM and MARC1 variants.


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    Publication History

    Article published online:
    26 January 2022

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