The causal associations between cancers and cardiovascular diseases: a two-sample bidirectional Mendelian randomization analysis

BACKGROUNDAssociations between cancer and cardiovascular disease (CVD) have been reported previously in observational studies. However, the causal relationship between the specific subspecies of the two diseases remains unclear. This study used a two-sample bidirectional MR study to investigate the causal relationship between different types of CVDs and the major types of malignancies and vice-versa. METHODS AND RESULTSWe extracted summary statistics for coronary atherosclerosis, hypertension, hypertrophic cardiomyopathy, heart failure, atrial fibrillation, stroke, and 14 common malignancies from published relevant genome-wide association studies as instrumental variables. We conducted two-sample bidirectional Mendelian randomization (MR) studies to assess the causal relationship between CVD and cancer in which the inverse variance weighting (IVW) method was the main method. Multiple comparison calibration, sensitivity analysis, and heterogeneity analysis were performed to improve the reliability and robustness of the results. The evidence from IVW analyses showed that genetically predicted coronary atherosclerosis was suggestively associated with a decreased risk of endometrial cancer (OR=0.053, 95% CI: 0.004-0.648, P=0.022); hypertension was suggestively associated with an increased risk of oral cavity/pharyngeal cancer (OR=14.872, 95% CI: 1.324-167.053, P=0.029); hypertrophic cardiomyopathy was suggestively associated with a decreased risk of brain cancer (OR=0.479, 95% CI: 0.257-0.890, P=0.020); any stroke was suggestively associated with a decreased risk of breast cancer (OR=0.798, 95% CI: 0.669-0.952, P=0.012) and prostate cancer (OR=0.844, 95% CI: 0.737-0.966, P=0.014) since their significance weakened after multiple testing. In the reverse MR analysis, bladder cancer was associated with an increased risk of coronary atherosclerosis (OR=1.426, 95% CI: 1.051-1.934, P= 0.023) and hypertension (OR=1.689, 95% CI: 1.115-2.557, P=0.013); pancreatic cancer was associated with an increased risk of any stroke (OR= 1.047, 95% CI: 1.005-1.090, P= 0.027), losing significance after multivariate testing. Prostate cancer was significantly associated with an increased risk of heart failure (OR= 1.030, 95% CI: 1.009-1.053, P= 0.006); cervical cancer was significantly associated with an increased risk of any stroke (OR= 8.751686e+03, 95% CI: 35.043-2.185650e+06, P= 0.001). CONCLUSIONSCausal relationships for specific types of CVD and cancer were found in this MR Study, although some were suggestive. This study provides ideas for the follow-up management of these two common chronic diseases. CLINICAL PERSPECTIVEO_ST_ABSWhat Is New?C_ST_ABSO_LISome observational studies have shown that cardiovascular diseases (CVDs) and cancer have complex causal relationships dominated by positive associations. However, the role of genetic factors in their comorbidities remains unclear. C_LIO_LIIn this study, by utilizing data from genome-wide association studies, we identified a significant genetic correlation between multiple groups of specific classes of CVDs and specific types of malignancy, along with the shared risk snp. Some of the results are contrary to previous reports and warrant further research. These findings could provide insights into the shared genetic architecture between CVD and cancer. C_LI What Are the Clinical Implications?This study adds to the understanding of the underlying causal relationships of different phenotypes of CVD and cancer, with implications for the prediction and prevention of these common comorbidities.