Z Gastroenterol 2021; 59(08): e205-e206
DOI: 10.1055/s-0041-1733609
Grundlagenforschung Pankreas und Leber
Mittwoch, 15. September 2021, 12:00-13:20 Uhr, After-Work-Stream: Kanal 1
Gastroenterologische Onkologie

Variants APOE (rs429358) and TM6SF2 (rs187429064) confer risk to hepatocellular carcinoma

H Innes
1   Glasgow Caledonian University, School of Health and Life Sciences, Glasgow, Vereinigtes Königreich
,
HD Nischalke
2   Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Biomedizinisches Zentrum (BMZ), Bonn, Deutschland
,
J Rosendahl
3   Universitätsklinikum Halle (Saale), Poliklinik für Innere Medizin I, Halle (Saale), Deutschland
,
KH Weiss
4   Universitätsklinikum Heidelberg, Heidelberg, Deutschland
,
S Sulk
5   Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik I, Dresden, Deutschland
,
S Müller
4   Universitätsklinikum Heidelberg, Heidelberg, Deutschland
,
J Fischer
6   Universitätsklinikum Leipzig, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Leipzig, Deutschland
,
M Casper
7   Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 2, Homburg, Deutschland
,
D Gotthardt
4   Universitätsklinikum Heidelberg, Heidelberg, Deutschland
,
F Lammert
7   Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 2, Homburg, Deutschland
,
PL Lutz
8   Universitätsklinikum Bonn, Bonn, Deutschland
,
G Semmler
9   Medical University of Vienna, Wien, Österreich
,
F Eyer
10   Technische Universität München, München, Deutschland
,
J von Felden
11   Universitätsklinikum Hamburg-Eppendorf, I. Medizinische Klinik und Poliklinik, Hamburg, Deutschland
,
A Link
12   Universitätsklinikum Magdeburg, Magdeburg, Deutschland
,
A Vogel
13   Medizinischen Hochschule Hannover, Hannover, Deutschland
,
IN Guha
14   University of Nottingham, NIHR Nottingham Biomedical Research Centre (BRC), Nottingham, Vereinigtes Königreich
,
J Marquardt
15   Universitätsklinikum Schleswig-Holstein (UKSH), Lübeck, Deutschland
,
J Trebicka
16   Universitätsklinikum Frankfurt, Medizinische Klinik 1 Sektion Translationale Hepatologie, Frankfurt, Deutschland
,
E Barnes
17   Oxford University, Nuffield Department of Medicine, Oxford, Vereinigtes Königreich
,
L Valenti
18   University of Milan, Department of Pathophysiology and Transplantation, Mailand, Italien
,
C Datz
19   Krankenhaus Oberndorf, Oberndorf, Österreich
,
W Irving
14   University of Nottingham, NIHR Nottingham Biomedical Research Centre (BRC), Nottingham, Vereinigtes Königreich
,
Morling JR
20   University of Nottingham, School of Medicine, Nottingham, Vereinigtes Königreich
,
V Hamill
21   School of Health and Life Sciences, Glasgow, Vereinigtes Königreich
,
J McLauchlan
22   MRC-University of Glasgow Centre for Virus Research, Glasgow, Vereinigtes Königreich
,
J Benselin
14   University of Nottingham, NIHR Nottingham Biomedical Research Centre (BRC), Nottingham, Vereinigtes Königreich
,
A Marot
23   Université catholique de Louvain, Department of Gastroenterology and Hepatology, Yvoir, Belgien
,
V Pedergnana
24   Laboratoire MIVEGEC, Montpellier, Frankreich
,
T Reiberger
25   Universitätsklinik Wien, Gastroenterologie und Hepatologie, Wien, Österreich
,
A Ansari
26   Oxford University, Oxford NIHR Biomedical Research Centre, Oxford, Vereinigtes Königreich
,
C Schafmayer
27   Universitätsmedizin Rostock, Rostock, Deutschland
,
T Berg
28   Universitätsklinikum Leipzig, Leipzig, Deutschland
,
P Deltenre
29   Universitätsklinik Lausanne (CHUV), Lausanne, Schweiz
,
F Stickel
30   Universitätsspital Zürich, Zürich, Schweiz
,
J Hampe
31   Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Deutschland
,
S Buch
31   Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Deutschland
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Background and aims The host genetic background for hepatocellular carcinoma (HCC) is incompletelyunderstood. We aimed to determine if four germline genetic polymorphisms, rs429358in 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 and 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) and/or population controls. 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, 2070 HCC cases, 4958 cirrhosis controls, and 525779 population controls were included. The rs429358:C allele in APOE wassignificantly less frequent in HCC cases versus controls (per allele OR across allstudies: 0.68; 95%CI: 0.58-0.79; P =9.30×10-7). Rs187429064:G in TM6SF2 wassignificantly more common in HCC cases versus controls and exhibited the strongesteffect size (OR: 2.61;95%CI:1.97-3.39; P =1.4×10-11). In contrast, rs2792751:T inGPAM was not associated with HCC (OR:0.99; 95%CI:0.90-1.08; P =0.85), whilstrs2642438:A in MARC1 was less frequent in cases versus controls, but narrowlymissed 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.



Publication History

Article published online:
07 September 2021

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