Qiu Youjia, Xie Minjia, Song Bingyi, Wang Menghan, Ji Na, Yin Ziqian, Li Jinglin, Tang Xinling, Ma Chao, Wang Zhong
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Jiangsu Province, Suzhou, 215006, China.
Department of Neurology, The First Affiliated Hospital of Soochow University, Jiangsu Province, Suzhou, 215006, China.
Mol Neurobiol. 2025 Apr 30. doi: 10.1007/s12035-025-04979-2.
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), NGR1 (OR 1.15, 95% CI 1.10 to 1.20, p = 2.59 × 10), 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) 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.
鉴于既往流行病学研究中乳腺癌（BC）、选择性雌激素受体调节剂与脑膜瘤之间的潜在联系，本研究旨在通过孟德尔随机化方法对其进行调查。我们从最大规模的全基因组关联研究中提取了不同亚型BC的工具变量（IVs）。选择性雌激素受体调节剂的基因靶点来自药物-基因相互作用数据库。孟德尔随机化（MR）分析采用逆方差加权法评估因果关系。一系列敏感性分析和反向MR用于评估MR结果的稳定性。基因决定的雌激素受体（ER）阳性BC、管腔A型乳腺癌（比值比[OR]1.17，95%置信区间[CI]1.04至1.32，p = 0.01）和管腔B型乳腺癌（OR 1.20，95% CI 1.04至1.37，p = 0.009）与脑膜瘤的比值比增加相关（OR 1.18，95% CI 1.05至1.32，p = 0.005）。在选择性雌激素受体调节剂靶向基因中，细胞色素P450 2D6（CYP2D6）（OR 1.37，95% CI 1.23至1.54，p = 4.15×10⁻⁹）、神经生长因子1（NGR1）（OR 1.15，95% CI 1.10至1.20，p = 2.59×10⁻⁵）和微管相关蛋白tau（MAPT）（OR 10.20，95% CI 2.90至35.84，p = 0.0003）与脑膜瘤风险增加相关，而乳腺癌1号基因（BRCA1）（OR 0.67，95% CI 0.57至0.80，p = 4.88×10⁻⁴）与脑膜瘤风险呈负因果关联。敏感性分析和反向MR分析的结果证实了这些发现。这些发现提示了BC与脑膜瘤之间的因果关系，并确定了与脑膜瘤相关的潜在靶基因，这有利于早期识别和预防脑膜瘤风险。
