- AutorIn
- Stephan Buch Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, Germany#Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden
- Hamish InnesSchool of Health and Life Sciences, Glasgow Caledonian University School of Health and Life Sciences, Glasgow#NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham
- Philipp Ludwig LutzDepartment of Internal Medicine I, University of Bonn
- 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
- Titel
- Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis
- Untertitel
- results from a genome-wide case-control study
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-890129
- Quellenangabe
- Gut : an international journal of gastroenterology and hepatology
Erscheinungsjahr: 2022
Jahrgang: 72
Heft: 2
Seiten: 1-11
E-ISSN: 1468-3288 - Erstveröffentlichung
- 2022
- Abstract (EN)
- 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 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.
- Andere Ausgabe
- Link zum Artikel, der zuerst in der Zeitschrift „Gut : an international journal of gastroenterology and hepatology” erschienen ist.
DOI: 10.1136/gutjnl-2022-327196 - Freie Schlagwörter (DE)
- genetische Variation, TERT, hepatozelluläres Karzinom, alkoholbedingte Zirrhose
- Freie Schlagwörter (EN)
- enetic variation, TERT, hepatocellular carcinoma, alcohol-related cirrhosis
- Klassifikation (DDC)
- 610
- Verlag
- BMJ Publishing Group, London
- Förder- / Projektangaben
- Bundesministerium für Bildung und Forschung (BMBF)
Detaillierte Analyse der räumlichen Organisation der Entstehung des hepatozellulären Karzinoms (DEEP-HCC)
Systemmedizinisches Forschungsnetz zur Früherkennung und Prävention von Leberkrebs (LiSyM-Krebs)
ID: 031L0258A - Deutsche Forschungsgemeinschaft (DFG)
SFB 1382: Die Darm-Leber Achse – Funktionelle Zusammenhänge und therapeutische Strategien
Die Rolle des Darmmikrobioms bei der Dekompensation chronischer Lebererkrankungen mit Pfortaderhochdruck ((A09))
ID:  403224013 - Hessische Ministerium für Wissenschaft und Kunst (HMWK)
ID:  ENABLE - Hessische Ministerium für Wissenschaft und Kunst (HMWK)
ID:  ACLF-I - Schweizerischer Nationalfonds (SNF)
ID: 310030_169196 - Schweizerischen Stiftung für Alkoholforschung (SSA)
- UK Research and Innovation (EU)
MRC
Viral Hepatitis
ID:  MC_UU_12014/1 - UK Research and Innovation (EC)
MRC
Stratified Medicine to Optimise Treatment for Hepatitis C Virus Infection
ID:  MR/K01532X/1 - Cancer Research UK (EC)
ID: C30358/ A29725 - Europäische Union (EC)
Autonomie im Alter (AiA)
Leber-Mikrobiota-Achse im Mittelpunkt des gesunden Alterns
(LiLife) - European Commission (EC)
MICROBiome-based biomarkers to PREDICT decompensation of liver cirrhosis and treatment response
(MICROB-PREDICT
)
ID: 825694 - Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa2-890129
- Veröffentlichungsdatum Qucosa
- 22.02.2024
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
- CC BY 4.0