Association of Breast Cancer and Selective Estrogen Receptor Modulators on the Risk of Meningioma: Insights from Mendelian Randomization

Considering the potential links between breast cancer (BC), selective estrogen receptor modulators, and meningioma in previous epidemiology studies, this study aimed to investigate them through the Mendelian randomization approach. We extracted instrumental variables (IVs) of different subtypes of BC from the largest genome-wide association study. Gene targets of SERMs were obtained from the Drug–Gene Interaction Database. Mendelian randomization (MR) analysis applied inverse variance weighted approach to evaluate causality. A series of sensitivity analyses and reverse MR were used to evaluate the stability of the MR results. Genetically determined estrogen receptor (ER) positive BC, luminal A-like breast cancer (OR 1.17, 95% CI 1.04 to 1.32, p = 0.01), and luminal B-like breast cancer (OR 1.20, 95% CI 1.04 to 1.37, p = 0.009) were associated with an increased odds ratio of meningioma (OR 1.18, 95% CI 1.05 to 1.32, p = 0.005). Among SERM-targeted genes, CYP2D6 (OR 1.37, 95% CI 1.23 to 1.54, p = 4.15 × 10− 8), NGR1 (OR 1.15, 95% CI 1.10 to 1.20, p = 2.59 × 10− 11), and MAPT (OR 10.20, 95% CI 2.90 to 35.84, p = 0.0003) were associated with increased meningioma risk, while BRCA1 (OR 0.67, 95% CI 0.57 to 0.80, p = 4.88 × 10− 6) showed negative causal association with meningioma risk. The outcome of the sensitivity analysis and reverse MR analysis corroborated the findings. These findings suggested a causal relationship between BC and meningioma, and identified potential target genes associated with meningioma, which was beneficial to early identification and prevention of meningioma risk.