Colorectal cancer and long-term exposure to trihalomethanes in drinking water: A multicenter case-control study in Spain and Italy

C.M. Villanueva, E. Gracia-Lavedan, C. Bosetti, E. Righi, A.J. Molina, V. Martín, E. Boldo, N. Aragonés, B. Perez-Gomez, M. Pollan, I.G. Acebo, J.M. Altzibar, A.J. Zabala, E. Ardanaz, R. Peiró, A. Tardón, M.D. Chirlaque, A. Tavani, J. Polesel, D. SerrainoF. Pisa, G. Castaño-Vinyals, A. Espinosa, N. Espejo-Herrera, M. Palau, V. Moreno, C. La Vecchia, G. Aggazzotti, M.J. Nieuwenhuijsen, M. Kogevinas

Research output: Contribution to journalArticlepeer-review


Background: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. oBjectives: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. Methods: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant’s residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). results: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. conclusions: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. © 2017, Public Health Services, US Dept of Health and Human Services. All rights reserved.
Original languageEnglish
Pages (from-to)56-65
Number of pages10
JournalEnvironmental Health Perspectives
Issue number1
Publication statusPublished - 2017


  • chloroform
  • cytochrome P450 2E1
  • drinking water
  • glutathione s transferase zeta 1
  • peptides and proteins
  • tap water
  • trihalomethane
  • unclassified drug
  • water pollutant
  • adult
  • aged
  • Article
  • bath
  • bromination
  • colorectal cancer
  • controlled study
  • drug concentration
  • drug exposure
  • female
  • fluid intake
  • genotype
  • human
  • Italy
  • major clinical study
  • male
  • multicenter study
  • priority journal
  • questionnaire
  • risk factor
  • Spain
  • analysis
  • chemistry
  • clinical trial
  • Colorectal Neoplasms
  • environmental exposure
  • procedures
  • statistics and numerical data
  • water management
  • Adult
  • Drinking Water
  • Environmental Exposure
  • Humans
  • Trihalomethanes
  • Water Pollutants, Chemical
  • Water Purification


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