The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma

Summary 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 Kingdo...

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Published in:Alimentary pharmacology & therapeutics 2023-09, Vol.58 (6), p.623-631
Main Authors: Innes, Hamish, Morgan, Marsha Y., Hampe, Jochen, Stickel, Felix, Buch, Stephan
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
cirrhosis
Diagnosis
Fatty liver
Gene polymorphism
Genetic diversity
Genetic factors
Genetic Predisposition to Disease
genetic susceptibility
Hepatocellular carcinoma
Humans
Liver cancer
Liver diseases
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Medical prognosis
Mortality
Multivariate analysis
Non-alcoholic Fatty Liver Disease
Polymorphism
Polymorphism, Single Nucleotide
prognosis
Survival
therapeutic target
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Summary:Summary 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 
ISSN:0269-2813
1365-2036
DOI:10.1111/apt.17638