Xiao Fangting, Xie Diya, Zhou Daosen, Yang Lihang, Liu Fengmin
Department of Breast Surgery, Fuzhou First General Hospital Affiliated with Fujian Medical University, Fuzhou, Fujian, China.
Department of General Surgery, Fuzhou First General Hospital Affiliated with Fujian Medical University, Fuzhou, Fujian, China.
Medicine (Baltimore). 2025 May 23;104(21):e42571. doi: 10.1097/MD.0000000000042571.
To investigate the link between Latent Autoimmune Diabetes in Adults (LADA) and breast cancer (BC) subtypes using Mendelian randomization (MR) and identify potential immunological mediators. We used MR with genetic variants as instruments, leveraging genome-wide association studies data from Europeans to assess the relationship between LADA and BC subtypes. The study evaluated the mediating role of immune cells and employed methods like inverse variance weighted, MR Egger, and MR-PRESSO to ensure robust results. LADA showed a negative association with overall BC, human epidermal growth factor receptor 2-positive BC, and estrogen receptor-positive BC. The FinnGen Biobank replication and meta-analysis confirmed these inverse relationships. CD11c on CD62L+ myeloid dendritic cells mediated the relationship between LADA and BC risk. Our study indicated a negative association between LADA and BC development, especially for human epidermal growth factor receptor 2-positive and estrogen receptor-positive subtypes, with CD11c on CD62L+ myeloid dendritic cells as a key mediator. These findings suggest potential mechanisms for LADA's influence on BC risk and highlight opportunities for targeted prevention and treatment.
利用孟德尔随机化(MR)研究成人隐匿性自身免疫性糖尿病(LADA)与乳腺癌(BC)亚型之间的联系,并确定潜在的免疫介导因子。我们使用以基因变异为工具的MR,利用来自欧洲人的全基因组关联研究数据来评估LADA与BC亚型之间的关系。该研究评估了免疫细胞的中介作用,并采用了逆方差加权、MR Egger和MR-PRESSO等方法以确保结果的稳健性。LADA与总体BC、人表皮生长因子受体2阳性BC和雌激素受体阳性BC呈负相关。芬兰生物银行的复制和荟萃分析证实了这些反向关系。CD62L+髓样树突状细胞上的CD11c介导了LADA与BC风险之间的关系。我们的研究表明LADA与BC发生之间存在负相关,特别是对于人表皮生长因子受体2阳性和雌激素受体阳性亚型,CD62L+髓样树突状细胞上的CD11c是关键介导因子。这些发现提示了LADA影响BC风险的潜在机制,并突出了针对性预防和治疗的机会。