Risk of bladder cancer by disease severity in relation to metabolic factors and smoking; a prospective pooled cohort study of 800,000 men and women

Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811 633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic+diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2 983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% CI 1.06-1.27] and 1.09 [1.02-1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82-0.99]). The associations for BMI and BP differed between men and women (Pinteraction ≤0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01-1.18], 1.14 [1.02-1.25], and 1.30 [1.12-1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02-1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04-3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. This study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness. This article is protected by copyright. All rights reserved.

International journal of cancer. 2018 May 14 [Epub ahead of print]

Stanley Teleka, Christel Häggström, Gabriele Nagel, Tone Bjørge, Jonas Manjer, Hanno Ulmer, Fredrik Liedberg, Sara Ghaderi, Alois Lang, Håkan Jonsson, Staffan Jahnson, Marju Orho-Melander, Steinar Tretli, Pär Stattin, Tanja Stocks

Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden., Department of Biobank Research, Umeå University, Umeå, Sweden., Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany., Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway., Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden., Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria., Division of Urological Research, Institution of Translational Medicine, Lund University, Malmö, Sweden., Vorarlberg Cancer Registry, Agency for Preventive and Social Medicine, Bregenz (aks), Austria., Department of Radiation Sciences, Umeå University, Umeå, Sweden., Department of Urology and IKE, Linköping University, Linköping, Sweden., Cancer Registry of Norway, Oslo, Norway., Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.