Clopidogrel use and primary liver cancer causality: a Mendelian randomisation-based study

Abstract

Abstract: Objective: To investigate the potential causal relationship between clopidogrel usage and the incidence of primary liver cancer, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), using a two-sample Mendelian randomisation (MR) approach.
Methods: Data sets on clopidogrel use (n=462 933), HCC (n=161 323), ICC (n=476 091) and cHCC-CCA (n=218 488) were obtained from the GWAS catalog database from 2018 to 2021. The causal association of clopidogrel use with HCC, ICC and cHCC-CCA was assessed using inverse variance weighting as the primary method, heterogeneity analysed by MR-Egger Q test and IVW Q test, the presence of outliers assessed by funnel plots, reliability of the results assessed by leave-one-out rows, and horizontal multivariate validity tested by MR-Egger intercept test.
Results: In this study, eight SNPs strongly associated with clopidogrel use were screened as instrumental variables (IV). The results of the inverse variance weighted and median weighted analyses showed that there was a negative correlation between clopidogrel use in patients and the occurrence of HCC (OR<1, P<0.05), and there was no significant correlation between the use of clopidogrel in patients and the occurrence of both ICC and cHCC-CCA (P>0.05). The results of the heterogeneity test showed no heterogeneity in the causal relationship between clopidogrel use and HCC (P>0.05), and the results of the MR-Egger intercept test indicated that no horizontal pleiotropy was detected between clopidogrel use and HCC (P>0.05). The leave-one-out method of assessment showed no significant effect on the results of the Mendelian randomisation analysis after deleting individual SNPs one by one.The results of funnel plot analysis showed a symmetrical distribution of the selected IV, suggesting no significant bias in the results.
Conclusion: ClopidogrelusewasassociatedwithareducedriskofHCC, but did not reduce the risk of ICC and cHCC-CCA.

Key words: Clopidogrel, Hepatocellular carcinoma, Intrahepatic cholangiocarcinoma, Combined hepatocellular-cholangiocarcinoma, Two-sample Mendelian randomisation

Yang Wei, Yang Shuhong. Clopidogrel use and primary liver cancer causality: a Mendelian randomisation-based study[J]. Electronic Journal of Liver Tumor, 2026, 13(1): 33-38.

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