乳腺癌与其雌激素受体（ER）亚型与中性粒细胞减少症和粒细胞缺乏症之间的因果关系尚不清楚。在两样本孟德尔随机化（MR）中，我们使用了逆方差加权（IVW）、贝叶斯加权MR（BWMR）、MR-Egger 、加权中位数、简单模式和加权模式方法，用于分析 ER 阳性乳腺癌、ER 阴性乳腺癌、整体乳腺癌以及药物引起的中性粒细胞减少症和粒细胞缺乏症的因果关系。为了验证结果，我们使用来自不同数据库的中性粒细胞减少症的 GWAS 数据再次进行了分析。在多变量 MR (MVMR) 中，我们评估了 ER 阳性和 ER 阴性乳腺癌对因果关系的独立影响。两个样本 MR 分析显示 ER 阳性乳腺癌之间存在因果关系（IVW 比值比 (OR) = 1.319， P = 7.580 × 10-10)，ER阴性乳腺癌(OR = 1.285，P = 1.263 × 10-4)，总体乳腺癌(OR = 1.418，P = 2.123 × 10-13)，以及药物诱导的乳腺癌中性粒细胞减少症ER阳性乳腺癌（OR = 1.349，P = 1.402 × 10-7）、ER阴性乳腺癌（OR = 1.235，P = 7.615 × 10-3）、总体乳腺癌（OR = 1.429）之间存在因果关系，P = 9.111 × 10-10)，以及中性粒细胞减少症。同样，ER阳性乳腺癌（OR = 1.213，P = 5.350 × 10-8），ER阴性乳腺癌（OR = 1.179，P = 1.300 × 10-3）和整体乳腺癌（OR = 1.275，P = 8.642 × 10-11)也与粒细胞缺乏症存在因果关系。 MVMR分析显示，ER阳性乳腺癌与药物引起的中性粒细胞减少症（OR = 1.233，P = 4.188 × 10-4）、中性粒细胞减少症（OR = 1.283，P = 6.363 × 10-4）和粒细胞缺乏症（OR = 1.142，P = 4.549 × 10-3)。异质性分析和多效性检验表明我们的结果是可靠的。我们的研究为乳腺癌与其雌激素受体亚型和中性粒细胞减少症之间的因果关系提供了遗传证据。在临床实践中，除了关注治疗因素外，还应额外关注乳腺癌患者，以避免严重中性粒细胞减少症。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

The causal relationship between breast cancer and its estrogen receptor (ER) subtypes and neutropenia and agranulocytosis is unclear.In two-sample Mendelian randomization (MR), we used inverse variance weighting (IVW), Bayesian weighted MR (BWMR), MR-Egger, weighted median, simple mode, and weighted mode methods to analyze causality for ER-positive breast cancer, ER-negative breast cancer, overall breast cancer, and drug-induced neutropenia and agranulocytosis. To validate the results, we performed the analysis again using GWAS data on neutropenia from different databases. In multivariable MR (MVMR), we assessed the independent effects of ER-positive and ER-negative breast cancer on causality.Two-sample MR analysis showed a causal relationship between ER-positive breast cancer (IVW odds ratio (OR) = 1.319, P = 7.580 × 10-10), ER-negative breast cancer (OR = 1.285, P = 1.263 × 10-4), overall breast cancer (OR = 1.418, P = 2.123 × 10-13), and drug-induced neutropenia and a causal relationship between ER-positive breast cancer (OR = 1.349, P = 1.402 × 10-7), ER-negative breast cancer (OR = 1.235, P = 7.615 × 10-3), overall breast cancer (OR = 1.429, P = 9.111 × 10-10), and neutropenia. Similarly, ER-positive breast cancer (OR = 1.213, P = 5.350 × 10-8), ER-negative breast cancer (OR = 1.179, P = 1.300 × 10-3), and overall breast cancer (OR = 1.275, P = 8.642 × 10-11) also had a causal relationship with agranulocytosis. MVMR analysis showed that ER-positive breast cancer remained causally associated with drug-induced neutropenia (OR = 1.233, P = 4.188 × 10-4), neutropenia (OR = 1.283, P = 6.363 × 10-4), and agranulocytosis (OR = 1.142, P = 4.549 × 10-3). Heterogeneity analysis and pleiotropy test showed that our results were reliable.Our study provides genetic evidence for a causal association between breast cancer and its estrogen receptor subtypes and neutropenia. In clinical practice, in addition to focusing on therapeutic factors, additional attention should be given to breast cancer patients to avoid severe neutropenia.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.