Objective: The aim of the study was to investigate the causal relationship between aspirin use and the risk of endometrial endometrioid cancer (EEC) using two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) study.
Materials and methods: A TSMR analysis was conducted to estimate the potential causal relationship between aspirin use and the risk of EEC using genome-wide data from Genome-wide association study (GWAS). The causal association between aspirin use and EEC was further analyzed by MVMR analysis after adjusting for various factors such as obesity, hypertension, diabetes, and infertility. The single nucleotide polymorphism (SNP) data associated with aspirin use and EEC was obtained from the GWAS catalog database.
Results: A total of six SNPs were included as instrumental variables in TSMR, which showed that taking aspirin reduced the risk of EEC [OR = 0.02, 95% CI = 0-0.28, p = 0.005, inverse variance weighted (IVW) method]. Besides, the results of the weighted median (WME) method, weighted mode, and simple mode were consistent with the results shown by the IVW method. After further using the MVMR method, the causal association of aspirin use and prevention of EEC onset remained significant after adjusting for the effects of obesity, hypertension, and diabetes (OR = 0.076, 95% CI = 0.007-0.793, p = 0.031). Sensitivity analyses, including heterogeneity, horizontal multiplicity, and leave-one-out tests, showed the reliability of the instrumental variables, proving that the results were reliable and not significantly biased.
Conclusions: Taking aspirin can reduce the risk of EEC morbidity, and it is expected to be of great significance for the early prevention and treatment of endometrial cancer by exploring the biological mechanism of aspirin on endometrioid cancer at a deeper level.