Long Yongjing, Huang Runze, Li Wei
Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Discov Oncol. 2025 Aug 25;16(1):1619. doi: 10.1007/s12672-025-03457-4.
Breast cancer, as a common malignant tumor in women, has not been fully elucidated in terms of its pathogenesis. The comorbidity between heart failure and breast cancer has attracted researchers' attention, while inflammatory factors and various cancer-related molecular pathways may play important roles in this association.
This study employed Mendelian randomization (MR) methodology, using multiple single nucleotide polymorphisms (SNPs) as instrumental variables, to investigate the genetic association between breast cancer and heart failure. Additionally, we further analyzed the relationships between different breast cancer subtypes.
The study found a significant positive genetic association between breast cancer and heart failure risk, which was consistently verified across different breast cancer subtypes. Various cancer-related molecular pathways showed different degrees of association with breast cancer risk: activation of KRAS, SHH, EGFR, and VEGF pathways was associated with increased breast cancer risk; activation of CASP8 apoptosis pathway and MITK/ATM DNA repair pathway may have protective effects; the AANAT (melatonin synthesis-related) pathway showed significant protective effects; while the NQO/NRF2 oxidative stress pathway exhibited dual roles.
This study aimed primarily to investigate the potential genetic association between breast cancer and heart failure using MR. Secondary objectives included exploring associations between breast cancer subtypes and heart failure, as well as examining the involvement of inflammatory and cancer-related molecular pathways.
乳腺癌作为女性常见的恶性肿瘤，其发病机制尚未完全阐明。心力衰竭与乳腺癌的合并症已引起研究人员的关注，而炎症因子和各种癌症相关分子途径可能在这种关联中发挥重要作用。
本研究采用孟德尔随机化（MR）方法，使用多个单核苷酸多态性（SNP）作为工具变量，研究乳腺癌与心力衰竭之间的遗传关联。此外，我们进一步分析了不同乳腺癌亚型之间的关系。
研究发现乳腺癌与心力衰竭风险之间存在显著的正遗传关联，这在不同乳腺癌亚型中得到了一致验证。各种癌症相关分子途径与乳腺癌风险呈现不同程度的关联：KRAS、SHH、EGFR和VEGF途径的激活与乳腺癌风险增加相关；CASP8凋亡途径和MITK/ATM DNA修复途径的激活可能具有保护作用；AANAT（褪黑素合成相关）途径显示出显著的保护作用；而NQO/NRF2氧化应激途径则表现出双重作用。
本研究主要旨在利用MR研究乳腺癌与心力衰竭之间潜在的遗传关联。次要目标包括探索乳腺癌亚型与心力衰竭之间的关联，以及研究炎症和癌症相关分子途径的参与情况。
