Schistosoma haematobium infection can lead to squamous cell carcinomas (SCC) of the bladder. Whether this also applies to more common urinary tract infections (UTIs) is unclear. We therefore aimed to investigate the association between UTIs, reflected by use of specific antibiotics, and risk of SCC of the bladder. We conducted a Danish nationwide case-control study and identified histologically verified bladder cancer cases (2000-2015; n=12,271) and age- and sex-matched cancer-free controls. We computed odds ratios (ORs) with 95% confidence intervals (CI) associating use of UTI-specific antibiotics with SCC bladder cancer, using conditional logistic regression. We applied a two-year lag-time to minimize reverse causation. To aid interpretation, similar analyses were performed for other bladder cancer types and other antibiotics. We identified 333 SCC cases (2.7% of all bladder cancers). Compared with no use (0-1 prescriptions), high-use (≥10 prescriptions) of UTI-specific antibiotics was associated with SCC with an OR of 11.4 (CI 7.6-17.2) and a clear dose-response pattern (ptrend <0.001). Use of phenoxymethylpenicillin, an antibiotic not used against UTIs, was not associated with SCC after adjustment for use of UTI-specific antibiotics (OR 0.5). Further, UTI-specific antibiotic use was not associated with urothelial carcinomas (n=11,029; OR 1.13; CI 0.97-1.32). Excluding patients with known urogenital disease did not influence the SCC estimates (overall OR 10.8; CI 6.2-18.9). Data on smoking were lacking, however, a quantitative bias analysis suggested this to be of limited importance. In conclusion, common UTIs are strongly, dose-dependently, and specifically associated with risk of SCC of the bladder. This article is protected by copyright. All rights reserved.
International journal of cancer. 2019 Dec 21 [Epub ahead of print]
Anton Pottegård, Kasper Bruun Kristensen, Søren Friis, Jesper Hallas, Jørgen Bjerggaard Jensen, Mette Nørgaard
Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark., Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark., Department of Urology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark., Department of Clinical Epidemiology, Institute of Clinical Medicine, Arhus University Hospital, Aarhus, Denmark.