Article Text

Download PDFPDF
Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case–control studies
  1. N Costet1,
  2. C M Villanueva2,3,4,
  3. J J K Jaakkola5,
  4. M Kogevinas2,4,6,7,
  5. K P Cantor8,
  6. W D King9,
  7. C F Lynch10,
  8. M J Nieuwenhuijsen2,4,6,
  9. S Cordier1
  1. 1Institut National de la Santé et de la Recherche Médicale (INSERM), U625, University of Rennes I, IFR-140, Groupe d'Etude sur la Reproduction chez l'Homme et le Mammifère, Rennes, France
  2. 2Center for Research in Environmental Epidemiology, Barcelona, Spain
  3. 3Municipal Institute of Medical Research (Institut Municipal d'Investigació Mèdica-Hospital del Mar), Barcelona, Spain
  4. 4Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain
  5. 5Center for Environmental and Respiratory Health Research, Institute of Health Sciences, University of Oulu, Oulu, Finland
  6. 6Municipal Institute of Medical Research, Barcelona, Spain
  7. 7National School of Public Health, Athens, Greece
  8. 8KP Cantor, Environmental LLC, Silver Spring, Maryland, USA
  9. 9Department of Community Health and Epidemiology, Queen's University, Kingston, Ontario, Canada
  10. 10Department of Epidemiology, The University of Iowa, Iowa City, Iowa, USA
  1. Correspondence to Nathalie Costet, GERHM INSERM U625, Batiment 13, Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes, France; nathalie.costet{at}


Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection practices and DBPs occurrence between both continents, specific risk estimates for bladder cancer in relation to DBPs exposure for European populations were needed. We conducted a pooled and a two-stage random-effect meta-analyses of three European case-control studies from France, Finland, and Spain (5467 individuals: 2381 cases and 3086 controls). Individual exposure to THMs was calculated combining information on residential history, estimates of the average total THMs (TTHM) level in tap water at the successive residences and personal water consumption. A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 μg/l (OR=1.47 (1.05; 2.05)) when compared to men exposed to levels ≤ 5 μg/l. The linear trend of the exposure-risk association was significant (p=0.01). Risks increased significantly for exposure levels above 25 μg/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion. There was no evidence of a differential exposure-response relation for TTHM and bladder cancer in Europe and North America. Consequently, a global exposure-risk relation based on 4351 cases and 7055 controls is now available.

  • Bladder cancer
  • disinfection by-products
  • trihalomethanes
  • meta-analysis
  • Europe
  • cancer
  • urological
  • meta-analysis
  • water

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding European Commission—the work was funded as part of the Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water in Europe (HIWATE) project, which is a three and a half year Specific Targeted Research Project, funded under the EU Sixth Framework Programme for Research and Technological Development by the Research Directorate-Biotechnology, Agriculture and Food Research Unit (Contract no Food-CT-2006-036224).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.