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Dominique S. Michaud,^1,2,3 Manolis Kogevinas,^4,5 Kenneth P. Cantor,³ Cristina M. Villanueva,⁴ Monteserrat Garcia-Closas,³ Nathaniel Rothman,³ Nuria Malats,⁴ Francisco X. Real,^4,6 Consol Serra,^6,7 Reina Garcia-Closas,⁸ Adonina Tardon,⁹ Alfredo Carrato,¹⁰ Mustafa Dosemeci,³ and Debra T. Silverman³

¹Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; ²Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; ³Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; ⁴Centre for Research in Environmental Epidemiology, Municipal Institute of Medical Research, Barcelona, Spain; ⁵Medical School, University of Crete, Heraklion, Greece; ⁶Universitat Pompeu Fabra, Barcelona, Spain; ⁷Consorci Hospitalari Parc Taulí, Sabadell, Spain; ⁸Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain; ⁹Universidad de Oviedo, Oviedo, Spain; ¹⁰Hospital General Universitario de Elche, Elche, Spain

Abstract
Background: Findings on water and total fluid intake and bladder cancer are inconsistent ; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case–control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk.

Objectives: We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case–control study in Spain.

Methods: A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders.

Results: Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62 ; 95% confidence interval (CI) , 0.40–0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47 ; 95% CI, 0.33–0.66 ; p for trend < 0.0001) , but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure ; we found no statistical interaction (p for interaction = 0.13) .

Conclusion: Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level.

Key words: bladder cancer, case–control study, chlorination by-products, fluid intake, water intake. Environ Health Perspect 115:1569–1572 (2007) . doi:10.1289/ehp.10281 available via http://dx.doi.org/ [Online 29 August 2007]

Address correspondence to D. Michaud, Harvard School of Public Health, Kresge 920, 677 Huntington Ave., Boston, MA 02115 USA. Telephone: (617) 432-4508. Fax (617) 566-7805. E-mail: dmichaud@hsph.harvard.edu

Participating Study Centers in Spain: Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona - Coordinating Center ; Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona ; Hospital Germans Tries i Pujol, Badalona, Barcelona ; Hospital de Sant Boi, Sant Boi, Barcelona ; Centre Hospitalari Parc Taulí, Sabadell, Barcelona ; Centre Hospitalari i Cardiològic, Manresa, Barcelona ; Hospital Universitario, La Laguna, Tenerife ; Hospital La Candelaria, Santa Cruz, Tenerife ; Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Alicante ; Universidad de Oviedo, Oviedo, Asturias ; Hospital San Agustín, Avilés, Asturias ; Hospital Central Covadonga, Oviedo, Asturias ; Hospital Central General, Oviedo, Asturias ; Hospital de Cabueñes, Gijón, Asturias ; Hospital de Jove, Gijón, Asturias ; Hospital de Cruz Roja, Gijón, Asturias ; Hospital Alvarez-Buylla, Mieres, Asturias ; Hospital Jarrio, Coaña, Asturias ; and Hospital Carmen y Severo Ochoa, Cangas, Asturias.

We thank L. Carroll and D. Campbell (Information Management Services Inc., Silver Spring, MD) for their support in study and data management.

The authors declare they have no competing financial interests.

Received 20 March 2007 ; accepted 29 August 2007.