Association between antithrombotic agents use and hepatocellular carcinoma risk: a two-sample Mendelian randomization analysis

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Multiple observational studies demonstrated a negative correlation between the use of antithrombotic agents and the risk of HCC. However, the precise causal relationship between these factors remains uncertain. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to assess the causal link between these two factors. Method: The summary statistics of single nucleotide polymorphisms (SNPs) associated with the use of antithrombotic agents were acquired from a genome-wide association study (GWAS) performed on individuals of European descent, as well as from the GWAS on the UK Biobank. A two-sample MR analysis was performed using the inverse variance weighting (IVW), the weighted median estimate, the MR-Egger regression, and the weighted-mode estimate. The robustness of the primary findings was assessed by sensitivity analysis. Results: Ten SNPs associated with the use of antithrombotic agents were selected as instrumental variables. The MR analysis performed using the four methods mentioned above revealed a negative correlation between the use of antithrombotic agents and HCC. The other methods also produced similar results. No heterogeneity and horizontal pleiotropy were found. Conclusion: Our findings suggested an inverse association of antithrombotic agents with the risk of HCC.