No evidence for a genetic causal effect of breast cancer on venous thromboembolism: a mendelian randomization study

Abstract

Active cancer is known to contribute to venous thromboembolism (VTE), but the cause-and-effect association of breast cancer on VTE is not yet clear. In order to investigate the possible causal relationships, we used a Mendelian randomization analysis. Data for generically predicted breast cancer were identified based on the BCAC consortium. A meta-analysis of genome-wide association study (GWAS) comprising 1,500,861 participants for VTE as well as data from the FinnGen study for VTE, DVT and PE was used for the causal-effect estimation. Our primary method was inverse-variance weighted (IVW), and our supplementary methods included weighted median and MR-Egger. We also carried out sensitivity analysis for the study. No evidence of causal-effect was detected of overall breast cancer on VTE in both the GWAS meta-analysis (OR=1.01, 95%CI:0.98-1.04, p = 0.495) and the FinnGen consortium (OR=1.00,95%CI:0.96-1.04, p = 0.945). In addition, the presence of ER-positive or ER-negative disease did not significantly influence the incidence of VTE and its subtypes. In conclusion, no genetic cause-and-effect of breast cancer on VTE risk was detected in the large MR analysis.

Keywords: Breast cancer; Causal effect; Mendelian randomization; Venous thromboembolism.