Multi-omics analysis reveals the impact of thrombotic diseases on the occurrence and prognosis of Breast cancer

Venous thromboembolism (VTE) and breast cancer (BC) are two globally prevalent diseases that present significant public health challenges. Despite their impact, the potential genetic association between VTE and BC remains insufficiently investigated. Mendelian randomization (MR) analysis was performed to evaluate the causal influence of VTE on BC. Summary-based Mendelian randomization (SMR) identified BC-induced cis-eQTLs in blood samples, while weighted correlation network analysis (WGCNA) identified VTE-related genes. Colocalization analysis was subsequently conducted to ascertain whether the intersecting genes identified through SMR and WGCNA are implicated in both diseases. MR analysis revealed that VTE conditions, particularly deep vein thrombosis (OR = 1.009, 95 % CI: 1.004-1.014, p = 0.0002) and pulmonary embolism (OR = 1.295, 95 % CI: 1.016-1.650, p = 0.037), may act as risk factors for BC. Colocalization analysis identified three VTE-related genes KCNN4 (PH4 = 0.638), SLC22A5 (PH4 = 0.946), and ZBTB38 (PH4 = 0.945) as being closely associated with BC development. Additionally, ssGSEA analysis demonstrated that both SLC22A5 and KCNN4 were enriched in the IL-17 signaling pathway and exhibited strong correlations with immune cells. Finally, a VTE-related risk score model was constructed, indicating better outcomes in the low-VTE risk score group. This study demonstrated that VTE is closely associated with BC development and identified potential molecular pathways linking the two conditions.