Trihalomethanes in Drinking Water and Bladder Cancer Burden in the European Union

Background: Trihalomethanes (THMs) are widespread disinfection by-products (DBPs) in drinking water, and long-term exposure has been consistently associated with increased bladder cancer risk. Objective: We assessed THM levels in drinking water in the European Union as a marker of DBP exposure and estimated the attributable burden of bladder cancer. Methods: We collected recent annual mean THM levels in municipal drinking water in 28 European countries (EU28) from routine monitoring records. We estimated a linear exposure-response function for average residential THM levels and bladder cancer by pooling data from studies included in the largest international pooled analysis published to date in order to estimate odds ratios (ORs) for bladder cancer associated with the mean THM level in each country (relative to no exposure), population-attributable fraction (PAF), and number of attributable bladder cancer cases in different scenarios using incidence rates and population from the Global Burden of Disease study of 2016. Results: We obtained 2005-2018 THM data from EU26, covering 75% of the population. Data coverage and accuracy were heterogeneous among countries. The estimated population-weighted mean THM level was 11.7 μg/L [standard deviation (SD) of 11.2]. The estimated bladder cancer PAF was 4.9% [95% confidence interval (CI): 2.5, 7.1] overall (range: 0-23%), accounting for 6,561 (95% CI: 3,389, 9,537) bladder cancer cases per year. Denmark and the Netherlands had the lowest PAF (0.0% each), while Cyprus (23.2%), Malta (17.9%), and Ireland (17.2%) had the highest among EU26. In the scenario where no country would exceed the current EU mean, 2,868 (95% CI: 1,522, 4,060; 43%) annual attributable bladder cancer cases could potentially be avoided. Discussion: Efforts have been made to reduce THM levels in the European Union. However, assuming a causal association, current levels in certain countries still could lead to a considerable burden of bladder cancer that could potentially be avoided by optimizing water treatment, disinfection, and distribution practices, among other possible measures. https://doi.org/10.1289/EHP4495. This work was funded by the EU Seventh Framework Programme EXPOsOMICS Project (grant agreement no. 308610), Human Genetics Foundation agreement 17-080 ISG, and CIBER Epidemiología y Salud Pública (CIBERESP). ISGlobal is a member of the Centres de Recerca de Catalunya (CERCA) Programme, Generalitat de Catalunya. We would like to thank the members of the European Programme for Intervention Epidemiology Training (EPIET) Alumni Network (EAN) for their assistance in identifying appropriate national focal points in specific countries. We would also like to thank the people from the national and local authorities and universities for the provision of THM data: Sofie Dewaele (Leefmilieu Brussel-BIM/Bruxelles Environnement–IBGE Afd. Inspectie en verontreinigde bodems, Dpt. Geïntegreerde controles, Brussels, Belgium), Steven Vanderwaeren (Team Watervoorziening-en gebruik, Vlaamse Milieumaatschappij, Afdeling Operationeel Waterbeheer, Brussels, Belgium), Jurica Štiglić (Croatian National Institute of Public Health, Zagreb, Croatia), Outi Zacheus (National Institute for Health and Welfare, Kuopio, Finland), Carmelo Massimo Maida (University of Palermo, Italy), Anna Norata (Agenzia di Tutela della Salute Citta’ Metropolitana Milano, Italy), Marco Chiesa (Agenzia di Tutela della Salute della Val Padana-Sede Territoriale di Mantova, Italy), Vincenzo Clasadonte (Agenzia di Tutela della Salute della Val Padana-Sede Territoriale Cremona, Italy), Emilia Guberti (Local Health Authority, Bologna, Italy), Cinzia Govoni (Local Health Authority, Ferrara, Italy), Paolo Pagliai (Local Health Authority Romagna, Italy), Daniela de Vita (Local Health Authority, Reggio Emilia, Italy), Danila Tortorici (Regional Health and Social Agency, Emilia Romagna, Italy), Marco Schintu (University of Cagliari, Italy), Paolo Montuori (University of Napoli Federico II, Italy), Audrius Dedele (Department of Environmental Sciences, Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania), Stefan Cachia (Water Services Corporation, Malta), Roel C.H. Vermuelen (Institute of Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands), the Chief Sanitary Inspectorate (Poland), Luís Simas (Water Quality Department, Entidade Reguladora, Dos Serviços De Águas e Resíduos, Lisboa, Portugal), and Christina Forslund (Food Control Department, National Food Agency, Uppsala, Sweden). Finally, we would like to thank Charles F. Lynch (University of Iowa, USA), Sylvaine Cordier (Université de Rennes, Inserm, École des hautes études en santé Publique (EHESP), Rennes, France), Will D. King (Queen’s University, Kingston, Ontario, Canada), and Kenneth P. Cantor (National Cancer Institute, National Institutes of Health, Bethesda, USA) for allowing us to use the dose–exposure data from their study. We are grateful to Xavier Basagaña (ISGlobal) for statistical assistance.