Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
J Cancer Res Clin Oncol. 2024 Oct 22;150(10):470. doi: 10.1007/s00432-024-05960-7.
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.
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.
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.
Our findings suggested an inverse causal association of antithrombotic agents with the risk of HCC.
肝细胞癌（HCC）是全球最常见的原发性肝癌。多项观察性研究表明，抗血栓药物的使用与 HCC 风险之间呈负相关。然而，这些因素之间的确切因果关系仍不确定。因此，我们的研究使用两样本 Mendelian 随机化（MR）分析来评估这两个因素之间的因果关系。
与抗血栓药物使用相关的单核苷酸多态性（SNP）的汇总统计数据是从欧洲血统个体的全基因组关联研究（GWAS）中获得的。使用逆方差加权（IVW）、加权中位数估计、MR-Egger 回归和加权模式估计进行两样本 MR 分析。使用 MR-PRESSO、MR-Egger 回归、Cochran's Q 检验和单样本剔除分析对主要发现进行敏感性分析。
选择了与抗血栓药物使用相关的 10 个 SNP 作为工具变量。使用上述四种方法进行的 MR 分析表明，抗血栓药物的使用与 HCC 之间存在负向因果关系。基于逆方差加权（IVW）方法的单变量 MR 估计表明，抗血栓药物的使用与 HCC 之间存在负向因果关系[比值比（OR）0.444，95%置信区间（CI）0.279 至 0.707，P=0.001]。其他方法也得出了类似的结果。未发现异质性和水平偏倚。
我们的研究结果表明，抗血栓药物与 HCC 风险之间存在反向因果关系。
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