Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies

Introduction: The association of adiposity with prostate cancer specific mortality remains unclear. We examined how adiposity and its distribution relates to fatal prostate cancer by analysing data from UK Biobank, and conducting a dose-response meta-analysis to integrate existing prospective evidence. We also described the cross-sectional associations in UK Biobank of commonly used adiposity measurements with indices of adiposity estimated by imaging. Methods: 218,246 men from UK Biobank who were free from cancer at baseline were included and participants were followed-up via linkage to health administrative datasets. Body mass index (BMI), total body fat percentage (using bioimpedance), waist circumference (WC) and waist-to-hip ratio (WHR) were collected at recruitment. Risk of dying from prostate cancer (primary cause) by the different adiposity measurements was estimated using multivariable-adjusted Cox proportional hazards models. Results from this and other prospective cohort studies were combined in a dose-response meta-analysis. Results: In UK Biobank, 631 men died from prostate cancer over a mean follow-up of 11.5 years. The hazard ratios (HR) for prostate cancer death were 1.10 (95% confidence interval=1.00-1.21) per 5 kg/m2 higher BMI, 1.03 (0.96-1.11) per 5% increase in total body fat percentage, 1.09 (1.02-1.18) per 10 cm increase in WC, and 1.09 (1.02-1.16) per 0.05 increase in WHR. Our meta-analyses of prospective studies included 22,106 prostate cancer deaths for BMI, 642 for body fat percentage, 3,153 for WC and 1,611 for WHR, and the combined HRs for dying from prostate cancer for the increments above were 1.10 (1.08-1.13), 1.03 (0.96-1.11), 1.08 (1.04-1.12), and 1.07 (1.02-1.12), respectively. In up to 4,800 UK Biobank participants with magnetic resonance imaging and dual-energy X-ray absorptiometry, BMI and WC were strongly associated with imaging estimations of total and central adiposity (e.g. visceral fat, trunk fat), with associations marginally larger for WC. There might be ~1000 fewer prostate cancer deaths per year in the UK if the mean BMI in men was reduced by 5 kg/m2. Conclusion: Overall, we found that men with higher total and central adiposity had similarly higher risks of prostate cancer death, which may be biologically driven or due to differences in detection. In either case, these findings provide further reasons for men to maintain a healthy body weight.