eprintid: 10174045
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/17/40/45
datestamp: 2023-07-27 13:12:39
lastmod: 2023-07-27 13:12:39
status_changed: 2023-07-27 13:12:39
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Innes, Hamish
creators_name: Morgan, Marsha Y
creators_name: Hampe, Jochen
creators_name: Stickel, Felix
creators_name: Buch, Stephan
title: The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G91
keywords: cirrhosis, genetic factors, genetic susceptibility, liver cancer, mortality, prognosis, therapeutic target
note: Copyright © 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
abstract: BACKGROUND: The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear. AIM: To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis. METHODS: We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all-cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment. RESULTS: The final sample included 439 patients; 74% had either non-alcoholic fatty liver disease or alcohol-related liver disease. There were 321 deaths during a mean follow-up of 1.9 years per participant. Kaplan-Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively. In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all-cause mortality risk (aHR: 0.74; 95% CI: 0.61-0.90; p = 0.003). Other associated factors were Baveno stage 3-4 (aHR: 1.65; 95% CI: 1.05-2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17-0.37; p < 0.001). CONCLUSIONS: The rs72613567:TA polymorphism in HSD17B13 is not only associated with a reduction in the risk of developing HCC but with a survival benefit in HCC once established. Therapeutic inhibition of HSD17B13 may augment survival in individuals with HCC.
date: 2023-07-20
date_type: published
publisher: Wiley
official_url: https://doi.org/10.1111/apt.17638
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2039290
doi: 10.1111/apt.17638
medium: Print-Electronic
lyricists_name: Morgan, Marsha
lyricists_id: MYMOR45
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
funding_acknowledgements: C0825 [MRF]
full_text_status: public
publication: Alimentary Pharmacology and Therapeutics
event_location: England
issn: 0269-2813
citation:        Innes, Hamish;    Morgan, Marsha Y;    Hampe, Jochen;    Stickel, Felix;    Buch, Stephan;      (2023)    The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma.                   Alimentary Pharmacology and Therapeutics        10.1111/apt.17638 <https://doi.org/10.1111/apt.17638>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10174045/1/The%20rs72613567%20TA%20polymorphism%20in%20HSD17B13%20is%20associated%20with%20survival%20benefit.pdf