Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Multiple observational studies demonstrated a negative association 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. 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. Sensitivity analysis of the primary findings was performed using MR-PRESSO, MR-Egger regression, Cochran's Q test, and Leave-one-out 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 causal association between the use of antithrombotic agents and HCC. Univariate MR estimates based on the inverse variance weighting (IVW) method suggested a negative causal association between the use of antithrombotic agents and HCC [odds ratio (OR) 0.444, 95% confidence interval (CI) 0.279 to 0.707, P = 0.001]. The other methods also produced similar results. No heterogeneity and horizontal pleiotropy were found. CONCLUSION: Our findings suggested an inverse causal association of antithrombotic agents with the risk of HCC.