Long-term exposure to nitrate and trihalomethanes in drinking water and prostate cancer: a multicase–control study in Spain (MCC-Spain)

Donat-Vargas, Carolina; Kogevinas, Manolis; Castaño Vinyals, Gemma; Pérez-Gómez, Beatriz; Llorca, Javier; Vanaclocha-Espi, Mercedes; Fernandez-Tardon, Guillermo; Costas, Laura; Aragonés, Núria; Gómez-Acebo, Inés; Moreno, Víctor; Pollán, Marina; Villanueva, Cristina M.

doi:http://dx.doi.org/10.1289/ehp11391

Long-term exposure to nitrate and trihalomethanes in drinking water and prostate cancer: a multicase–control study in Spain (MCC-Spain)

Citation

Donat-Vargas C, Kogevinas M, Castaño-Vinyals G, Pérez-Gómez B, Llorca J, Vanaclocha-Espí M, et al. Long-term exposure to nitrate and trihalomethanes in drinking water and prostate cancer: a multicase–control study in Spain (MCC-Spain). Environ Health Perspect. 2023 Mar;131(3):037004. DOI: 10.1289/ehp11391

Abstract

Nitrate and trihalomethanes (THMs) in drinking water are widespread and are potential human carcinogens. We evaluated the association between drinking-water exposure to nitrate and THMs and prostate cancer. During the period 2008–2013, 697 hospital-based incident prostate cancer cases (97 aggressive tumors) and 927 population-based controls were recruited in Spain, providing information on residential histories and type of water consumed. Average nitrate and THMs levels in drinking water were linked with lifetime water consumption to calculate waterborne ingestion. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models with recruitment area as random effect. Effect modification by tumor grade (Gleason score), age, education, lifestyle, and dietary factors was explored. Mean (plus or minus standard deviation±standard deviation) adult lifetime waterborne ingested nitrate (milligrams per day), brominated (Br)-THMs (micrograms per day), and chloroform (micrograms per day) were 11.5 (plus or minus 9.0±9.0), 20.7 (plus or minus 32.4±32.4), and 15.1 (plus or minus 14.7±14.7) in controls. Waterborne ingested nitrate greater than 13.8>13.8 vs. less than 5.5 milligrams per day<5.5mg/d was associated with an OR of 1.74 (95% CI: 1.19, 2.54) overall, and 2.78 (95% CI: 1.23, 6.27) for tumors with Gleason scores greater than or equal to 8≥8. Associations were higher in the youngest and those with lower intakes of fiber, fruit/vegetables, and vitamin C. Waterborne ingested THMs were not associated with prostate cancer. Residential tap water levels of Br-THMs and chloroform showed, respectively, inverse and positive associations with prostate cancer. Findings suggest long-term waterborne ingested nitrate could be a risk factor of prostate cancer, particularly for aggressive tumors. High intakes of fiber, fruit/vegetables and vitamin C may lower this risk. Association with residential levels but not ingested chloroform/Br-THM may suggest inhalation and dermal routes could be relevant for prostate cancer. https://doi.org/10.1289/EHP11391