Mendelian randomization study of breast cancer-related genes and their association with inflammatory signaling pathways.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.