Jens Marquardt

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About Jens Marquardt:

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SEEK ID: https://seek.lisym.org/people/151

Location: Germany

ORCID: Not specified

Joined: 14th Apr 2020

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Other Projects: LiSyM-Krebs Partnering (Universitätsklinikum Schleswig-Holstein, Campus Lübeck - Medizinische Klinik I)

LiSyM-Krebs ist ein nationales Forschungsnetz zur Früherkennung und Prävention von Leberkrebs, das unter Verwendung des systemmedizinischen Forschungsansatzes die komplexen, dynamischen Prozesse der Krankheitsprogression analysiert, um ausgehend von den Erkenntnissen aus dem Forschungsnetz LiSyM die Entstehung von Leberkrebs besser zu verstehen, vorherzusagen und im besten Fall sogar zu verhindern. LiSyM-Krebs setzt die erfolgreichen Forschungsaktivitäten der BMBF-Vorgängerprogramme ...

Projects: LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, SMART-NAFLD, DEEP-HCC network, C-TIP-HCC network

Web page: https://www.lisym-cancer.org

LiSyM-Krebs Partnering

This generic project is intended to be a forum for all LiSyM partner and external stakeholders interested in participating in the BMBF initiative LiSyM-Krebs.

Programme: LiSyM-Krebs - Systemmedizinisches Forschungsnetz zur Früherkennung und Prävention von Leberkrebs

Public web page: https://www.ptj.de/projektfoerderung/gesundheitsforschung/lisym-krebs

Organisms: Not specified

Universitätsklinikum Schleswig-Holstein, Campus Lübeck - Medizinische Klinik I

Country: Germany

City: Lübeck

Web page: https://www.uksh.de/index.php?id=1&lang=de&site=Med1_Luebeck

Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study

Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

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Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account …tors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case–control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10 −9 , OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10 −5 , OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10 −44 ). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Authors: Stephan Buch, Hamish Innes, Philipp Ludwig Lutz, Hans Dieter Nischalke, Jens U Marquardt, Janett Fischer, Karl Heinz Weiss, Jonas Rosendahl, Astrid Marot, Marcin Krawczyk, Markus Casper, Frank Lammert, Florian Eyer, Arndt Vogel, Silke Marhenke, Johann von Felden, Rohini Sharma, Stephen Rahul Atkinson, Andrew McQuillin, Jacob Nattermann, Clemens Schafmayer, Andre Franke, Christian Strassburg, Marcella Rietschel, Heidi Altmann, Stefan Sulk, Veera Raghavan Thangapandi, Mario Brosch, Carolin Lackner, Rudolf E Stauber, Ali Canbay, Alexander Link, Thomas Reiberger, Mattias Mandorfer, Georg Semmler, Bernhard Scheiner, Christian Datz, Stefano Romeo, Stefano Ginanni Corradini, William Lucien Irving, Joanne R Morling, Indra Neil Guha, Eleanor Barnes, M Azim Ansari, Jocelyn Quistrebert, Luca Valenti, Sascha A Müller, Marsha Yvonne Morgan, Jean-François Dufour, Jonel Trebicka, Thomas Berg, Pierre Deltenre, Sebastian Mueller, Jochen Hampe, Felix Stickel

Date Published: 5th Jan 2023

Publication Type: Journal

DOI: 10.1136/gutjnl-2022-327196

Citation: Gut 72(2):381-391

Created: 14th Sep 2023 at 16:13, Last updated: 14th Sep 2023 at 16:14

The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

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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 …rotein 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.

Authors: Hamish Innes, Hans Dieter Nischalke, Indra Neil Guha, Karl Heinz Weiss, Will Irving, Daniel Gotthardt, Eleanor Barnes, Janett Fischer, M. Azim Ansari, Jonas Rosendahl, Shang‐Kuan Lin, Astrid Marot, Vincent Pedergnana, Markus Casper, Jennifer Benselin, Frank Lammert, John McLauchlan, Philip L. Lutz, Victoria Hamill, Sebastian Mueller, Joanne R. Morling, Georg Semmler, Florian Eyer, Johann von Felden, Alexander Link, Arndt Vogel, Jens U. Marquardt, Stefan Sulk, Jonel Trebicka, Luca Valenti, Christian Datz, Thomas Reiberger, Clemens Schafmayer, Thomas Berg, Pierre Deltenre, Jochen Hampe, Felix Stickel, Stephan Buch

Date Published: 2022

Publication Type: Journal

DOI: 10.1002/hep4.1886

Citation: Hepatol Commun 6(5):1213-1226

Created: 14th Sep 2023 at 16:25, Last updated: 14th Sep 2023 at 16:25

Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance.

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

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BACKGROUND: The extracellular signal-regulated kinase (ERK) pathway regulates cell growth, and is hyper-activated and associated with drug resistance in hepatocellular carcinoma (HCC). Metabolic pathways …

Authors: Z. C. Nwosu, W. Pioronska, N. Battello, A. D. Zimmer, B. Dewidar, M. Han, S. Pereira, B. Blagojevic, D. Castven, V. Charlestin, P. Holenya, J. Lochead, C. De La Torre, N. Gretz, P. Sajjakulnukit, L. Zhang, M. H. Ward, J. U. Marquardt, M. P. di Magliano, C. A. Lyssiotis, J. Sleeman, S. Wolfl, M. P. Ebert, C. Meyer, U. Hofmann, S. Dooley

Date Published: 25th Apr 2020

Publication Type: Not specified

PubMed ID: 32330875

Citation: EBioMedicine. 2020 Apr;54:102699. doi: 10.1016/j.ebiom.2020.102699. Epub 2020 Apr 21.

Created: 29th Jun 2020 at 16:14

Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

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BACKGROUND AND AIMS: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular …

Authors: F. Stickel, P. Lutz, S. Buch, H. D. Nischalke, I. Silva, V. Rausch, J. Fischer, K. H. Weiss, D. Gotthardt, J. Rosendahl, A. Marot, M. Elamly, M. Krawczyk, M. Casper, F. Lammert, T. W. M. Buckley, A. McQuillin, U. Spengler, F. Eyer, A. Vogel, S. Marhenke, J. von Felden, H. Wege, R. Sharma, S. Atkinson, A. Franke, S. Nehring, V. Moser, C. Schafmayer, L. Spahr, C. Lackner, R. E. Stauber, A. Canbay, A. Link, L. Valenti, J. I. Grove, G. P. Aithal, J. U. Marquardt, W. Fateen, S. Zopf, J. F. Dufour, J. Trebicka, C. Datz, P. Deltenre, S. Mueller, T. Berg, J. Hampe, M. Y. Morgan

Date Published: 21st Oct 2019

Publication Type: Journal

PubMed ID: 31630428

Citation: Hepatology. 2020 Jul;72(1):88-102. doi: 10.1002/hep.30996. Epub 2020 May 20.

Created: 29th Sep 2020 at 12:52

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Jens Marquardt

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