Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Abstract

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

Keywords: Europe; association; cancer; cohort; epidemiology; hypertension; morphology; risk factors.

Figure 1. Flow diagram for EPIC participants included in the current study

n – number of participants; ca – number of cancer cases.

Figure 2. Forest plot of hazard ratios for continuous systolic and diastolic blood pressure

AC – adenocarcinoma; CNS – central nervous system; HCC – hepatocellular carcinoma; SCC – squamous cell carcinoma; SmallCC – small cell carcinoma; Vertical order – determined by the hazard ratio estimates for systolic blood pressure (SBP) of the main anatomical locations (dot symbols), each followed by the relevant specific locations or morphologies marked with ^ (+ symbols) (other locations, not included in those specified, are shown last); Hazard ratios – estimates (95% confidence intervals) (per 10mmHg higher blood pressure) derived from Cox proportional hazards models, stratified by study centre and age at recruitment (5-year categories) and adjusted for potential confounders and risk factors listed in Supplementary Table 2). For cervical AC (n=37): HR=0.96 (0.79-1.17) for SBP and HR=0.84 (0.59-1.19) for DBP and for other morphology in the cervix (non-SCC and non-AC) (n=41): HR=1.28 (1.10-1.48) for SBP and HR=1.53 (1.17-2.01) for DBP (considered only in the main analyses and excluded to avoid the larger confidence intervals dominating the plot); * p<0.05, ** p<0.005.

Figure 3. Forest plot of hazard ratios for dichotomous hypertension and antihypertensive treatment

AC – adenocarcinoma; CNS – central nervous system; HCC – hepatocellular carcinoma; SCC – squamous cell carcinoma; SmallCC – small cell carcinoma; Hypertension – defined as systolic blood pressure (SBP) ≥140 mmHg, or diastolic BP (DBP) ≥90 mmHg at the BP measurement visit, or self-reported history of hypertension; Antihypertensive treatment status – either self-reported or no treatment assumed if there was self-reported absence of diagnosis of hypertension; Cases – numbers per group (hypertension / no hypertension & treated / untreated hypertension); Vertical order – determined by the hazard ratio estimates for SBP of the main anatomical locations (dot symbols), each followed by the relevant specific locations or morphologies marked with ^ (+ symbols) (as per Figure 2) (other locations, not included in those specified, are shown last); Hazard ratios – estimates (95% confidence intervals) (per 10 mmHg higher BP) were derived from Cox proportional hazards models, stratified by study centre and age at recruitment (5-year categories) and adjusted for potential confounders and risk factors listed in Supplementary Table 2. For cervical AC (n=37): HR=1.23 (0.58-2.06) and for other morphology in the cervix (non-SCC and non-AC) (n=41): HR=1.82 (0.92-3.63) (considered only in the main analyses and omitted from the plot to avoid the larger confidence intervals dominating the plot); * p<0.05, ** p<0.005.