Assessing the Causal Effect of Blood Pressure on Renal Cancer in the UK Biobank via Mendelian Randomisation

1. Background Hypertension is associated with increasing risk of renal cancer in observational studies, but there is insufficient evidence on whether hypertension is a causal factor for renal cancer. Methods We analysed data from 313,520 individuals of White British ancestry aged 40-69 years at baseline from the UK Biobank prospective cohort. We used polygenic risk scores (PRS) for SBP and DBP, respectively, in Mendelian randomisation analyses to assess the causal effect of blood pressure on renal cancer. Our primary outcome is renal-parenchyma cancer, and we used bladder cancer as a negative control. We conducted additional sensitivity analyses, using individual SNPs from the PRS as instruments, to ensure the MR results are robust. Results Among the study population, 1159 participants developed renal-parenchyma cancer over the median of 12.5 years of follow-up. Every 5 mmHg increase in measured SBP and DBP was significantly associated with increased risk for renal-parenchyma cancer (HR: 1.04; 95% CI: 1.02-1.05; p < 0.001 and HR: 1.07; 95% CI: 1.03-1.10; p < 0.001 respectively). Consistent with observational association analyses, we observed statistically significant associations between each 5 mmHg genetically elevated BP and risk of renal-parenchyma cancer, with DBP (HR: 1.17; 95% CI: 1.07-1.27; p < 0.001) having a stronger association than SBP (HR: 1.09; 95% CI: 1.02-1.17; p = 0.009). These significant associations were maintained in sensitivity analyses. We observed a null association of genetically predicted blood pressure with bladder cancer. Conclusions These findings provide evidence that elevated BP is causally associated with renal-parenchyma cancer.