ArticleDiscover oncology2025
Association between allopurinol and hepatocellular carcinoma: analysis of genetic risk and patient survival.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDespite the widespread clinical use of allopurinol for managing hepatocellular carcinoma (HCC) and gout, its potential hepatotoxicity and its effect on the risk of HCC remain unclear. This study aimed to comprehensively assess the potential correlations between allopurinol exposure and HCC risk.
methodsWe utilized genome-wide association study data from the IEU OpenGWAS project as instrumental variables (IVs) for Mendelian randomization (MR) analysis to investigate the causal relationship between allopurinol and HCC. Subsequently, we investigated the potential mediating factors (gout, liver fat, and percentage of liver fat, etc.) between allopurinol use and HCC. Furthermore, we analyzed assessed survival outcomes using the Kaplan-Meier method to compare patient subgroups by differential Xanthine dehydrogenase (XDH) expression.
resultsMR analysis established a causal link between allopurinol use and increased HCC risk (OR: 1.013, 95% CI 1.004-1.023, p = 0.006). Causal relationships were also observed between gout (OR: 1.011, p = 0.008) and HCC. Mediation analysis indicated that gout mediated 61.6% of the effect of allopurinol on HCC. Survival analysis showed that higher expression of XDH was associated with improved survival of HCC patients (HR = 0.62, 95% CI 0.441-0.884, p = 0.008), indicating a 38% decrease in mortality risk compared to the lower expression group.
conclusionsThis study demonstrated a causal relationship between allopurinol use and an increased risk of HCC based on genetic evidence. Allopurinol should be used with caution in patients with or at risk for HCC.
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