The causal association between systolic blood pressure and breast cancer: a two sample Mendelian randomization study

Breast cancer (BC) is the leading cause of cancer incidence worldwide. Observational studies have suggested that hypertension may be a risk factor for BC. We tested whether systolic blood pressure (SBP) may influence BC and BC subtypes using a Mendelian randomisation (MR) approach. We used 334 genetic variants associated with SBP as an instrumental variable. Effect estimates were obtained from the UK biobank (n = 469,767; SNP-exposure estimates) and the Breast Cancer Association Consortium (BCAC) (122,977 cases and 105,974 controls; SNP-outcome estimates). We assessed BC sub-types including: Triple-negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2) positive, Luminal-A, Luminal-B, and Luminal-B HER2 negative. We used inverse variance weighted (IVW) as our primary analysis but conducted a series of sensitivity analyses to test the robustness of our findings. We created a restricted subset of SNPs by excluding SNPs associated with body mass index (BMI) and those with small effect sizes on the exposure, we also conducted multivariable mendelian randomisation analysis to control for adiposity as a potential confounder. For each 1 mm/Hg increase in SBP the estimated effect was OR 1.00 (0.93, 1.08) for overall BC, analyses of BC sub-types results also did not support a causal effect of SBP. Similarly, results of our sensitivity analyses did not show strong evidence of an association. The results of our study did not support a causal effect of SBP on overall BC or its sub-types.