Two-sample Mendelian randomization analysis of aspirin and the risk of gastric cancer
ZHANG Ying
ZHANG Wei
MA Yan
ZHANG Yueli
YANG Xiaorui
LIU Fanfan
Abstract：Objective To investigate the association between aspirin use and the risk of gastric cancer through two-sample Mendelian randomization(MR)analysis.Methods Two-sample MR analysis was conducted using publicly available GWAS data to investigate the potential causal relationship between aspirin and the risk of gastric cancer.SNPs strongly associated with aspirin were selected as instrumental variables,and MR analysis was performed using inverse variance weighting,weighted median,and MR Egger methods to investigate the relationship between aspirin and gastric cancer.Sensitivity analysis was also conducted to verify the reliability of the MR analysis results.Cochran′s Q test was used to assess heterogeneity,and the MR-Egger-intercept test was used to determine whether there was horizontal pleiotropy in the MR analysis results.Leave-one-out analysis was used to identify SNPs with potential influence.Results Seven SNPs strongly associated with aspirin were included as instrumental variables from publicly available GWAS data.The variance-weighted method results showed that aspirin use could reduce the risk of gastric cancer(OR=0.0039,95%CI:0.20-7.3910-5,P=0.0059).The weighted median method results were consistent with those of the variance-weighted method,indicating a negative causal association between aspirin use and the risk of gastric cancer.In the sensitivity analysis,the MR-Egger regression analysis result was P=0.88,suggesting that the selected SNPs did not have horizontal pleiotropy.Therefore,MR was an effective method for causal inference in this study.The Cochran′s Q test result was P=0.35,indicating no heterogeneity among SNPs and ensuring the robustness of the results.The MR-PRESSO analysis did not identify any outlier SNPs.The leave-one-out sensitivity analysis method results showed that no single SNP affected the MR analysis results.This indicated that the instrumental variables were reliable and had no obvious bias.Conclusion There is a causal relationship between aspirin and the risk of gastric cancer,and providing evidence for the protective effect of aspirin on gastric cancer,but the mechanism remains to be further discovered.
Keywords：Gastric cancerAspirinMendelian randomization analysisCausal relationship
Publication Date：2025-01-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 55-59 )