Abstract
A potential link between stenotic cardiovascular disease (ischemic stroke, peripheral artery disease, unstable angina) and the risk of breast cancer has been identified in clinical practice. However, it is unclear whether there is a causal relationship between the two. In this study, we applied univariate (UVMR) and multivariate Mendelian randomization (MVMR) to explain the possible link between stenotic cardiovascular disease and breast cancer pathogenesis at the genetic level, and pointed out that the study of the correlation between lipid metabolism and the pathogenesis of pan-cancerous species, such as breast cancer, is an innovative direction of basic experiments. Objective: This study explored the causal effect between a history of stenotic cardiovascular disease and the risk of breast cancer. Methods: Genome⁃wide association study (GWAS) data were selected from breast cancer (n = 8,013) and ischemic stroke (n = 159,840), Peripheral artery disease (n = 44,986), and unstable angina pectoris (n = 18,152), which corresponded to the same ethnicity and were from different regions. In this study, causal effects were assessed using inverse variance weighted (IVW), MR ⁃ Egger regression, and weighted median (WM); UVMR and MVMR studies were conducted using several other methods as supplements. Sensitivity analyses were conducted using Cochran's Q test, MR⁃Egger regression intercept term, MR⁃PRESSO, and leave-one-out method to assess the stability and reliability of the results. Results: In UVMR, ischemic stroke, peripheral artery disease, and unstable angina were positively associated with lower risk of breast cancer; in MVMR, unstable angina was independently and significantly causally associated with lower risk of breast cancer (OR = 0.996,95% CI:0.992–0.999, P = 0.007) . Conclusion:This study found that people with stenotic cardiovascular disease have a lower risk of developing breast cancer, and in addition, there may be some unique correlation between unstable angina and the pathogenesis of breast cancer. There may be a correlation between the collection of stenotic cardiovascular disease genes and the pathogenesis of pan-cancer species. Lipid metabolism-related gene collections or molecular pathways may be relevant to the pathogenesis of breast cancer and possibly pan-cancer.