The relationship between blood pressure and risk of renal cell carcinoma

Abstract

Background: The relation between blood pressure and kidney cancer risk is well established but complex and different study designs have reported discrepant findings on the relative importance of diastolic blood pressure (DBP) and systolic blood pressure (SBP). In this study, we sought to describe the temporal relation between diastolic and SBP with renal cell carcinoma (RCC) risk in detail.

Methods: Our study involved two prospective cohorts: the European Prospective Investigation into Cancer and Nutrition study and UK Biobank, including >700 000 participants and 1692 incident RCC cases. Risk analyses were conducted using flexible parametric survival models for DBP and SBP both separately as well as with mutuality adjustment and then adjustment for extended risk factors. We also carried out univariable and multivariable Mendelian randomization (MR) analyses (DBP: ninstruments = 251, SBP: ninstruments = 213) to complement the analyses of measured DBP and SBP.

Results: In the univariable analysis, we observed clear positive associations with RCC risk for both diastolic and SBP when measured ≥5 years before diagnosis and suggestive evidence for a stronger risk association in the year leading up to diagnosis. In mutually adjusted analysis, the long-term risk association of DBP remained, with a hazard ratio (HR) per standard deviation increment 10 years before diagnosis (HR10y) of 1.20 (95% CI: 1.10-1.30), whereas the association of SBP was attenuated (HR10y: 1.00, 95% CI: 0.91-1.10). In the complementary multivariable MR analysis, we observed an odds ratio for a 1-SD increment (ORsd) of 1.34 (95% CI: 1.08-1.67) for genetically predicted DBP and 0.70 (95% CI: 0.56-0.88) for genetically predicted SBP.

Conclusion: The results of this observational and MR study are consistent with an important role of DBP in RCC aetiology. The relation between SBP and RCC risk was less clear but does not appear to be independent of DBP.

Keywords: Mendelian randomization; RCC; diastolic blood pressure; kidney cancer; systolic blood pressure.

Figure 1

Hazard ratios for renal cell carcinoma from EPIC and UKB per standard deviation on diastolic and systolic blood pressure as a function of time from blood pressure measurement to diagnosis. Model-based HR point estimates are indicated for blood pressure measurements taken 10 years, 5 years and 2 months prior to diagnosis. Hazard ratios (HRs) were estimated using flexible parametric survival models for diastolic blood pressure (DBP) and systolic blood pressure (SBP), respectively, using follow-up time as the timescale, adjusted for age at baseline and additionally stratified by sex, country and cohorts. (A) DBP standard adjustment model; (B) DBP adjusted for SBP in addition to standard variables; (C) DBP adjusted for SBP, body mass index (BMI), hypertension, weekly alcohol intake (in grams) and smoking status in addition to standard variables; (D) SBP standard adjustment model; (E) SBP adjusted for DBP in addition to standard variables; (F) SBP adjusted for DBP, BMI, hypertension, weekly alcohol intake (in grams) and smoking status in addition to standard variables. In addition, histograms of number of RCC cases are shown. EPIC, European Prospective Investigation into Cancer and Nutrition; UKB, UK Biobank.

Figure 2

Long-term association between blood pressure and renal cell carcinoma risk and comparison with Mendelian randomization. (a) Diastolic blood pressure (DBP) or systolic blood pressure (SBP) minimally adjusted; (b) DBP or SBP adjusted with each other. MR, Mendelian randomization; IVW, inverse variance-weighted method; OR, odds ratio; HR, hazard ratio; EPIC, European Prospective Investigation into Cancer and Nutrition; UKB, UK Biobank.