TY  - INPR
SN  - 0269-2813
A1  - Innes, Hamish
A1  - Morgan, Marsha Y
A1  - Hampe, Jochen
A1  - Stickel, Felix
A1  - Buch, Stephan
N2  - 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.
KW  - cirrhosis
KW  -  genetic factors
KW  -  genetic susceptibility
KW  -  liver cancer
KW  -  mortality
KW  -  prognosis
KW  -  therapeutic target
AV  - public
ID  - discovery10174045
Y1  - 2023/07/20/
UR  - https://doi.org/10.1111/apt.17638
TI  - The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma
N1  - 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.
JF  - Alimentary Pharmacology and Therapeutics
PB  - Wiley
ER  -