title: Nitrate in drinking water and bladder cancer risk in Spain.
abstract: BACKGROUND
  Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables.
  
  
  METHODS
  We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview.
  
  
  RESULTS
  Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤ 5 mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤ 4 mg/day. Adjustment for several covariables showed similar results to crude analyses.
  
  
  CONCLUSIONS
  Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed.
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Nadia
authors.initials: N
authors.lastname: Espejo-Herrera
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Cantor
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Malats
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.affiliation: Universidad de Oviedo, Oviedo, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.affiliation: Hospital Universitario de Canarias, La Laguna, Spain.
authors.forename: Reina
authors.initials: R
authors.lastname: García-Closas
authors.affiliation: Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, Spain; Consorci Hospitalari Parc Taulí, Sabadell, Spain.
authors.forename: Consol
authors.initials: C
authors.lastname: Serra
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; National School of Public Health, Athens, Greece.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Electronic address: cvillanueva@creal.cat.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Villanueva
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D016022:Case-Control Studies; D002415:Cats; D060766:Drinking Water / Q000032:analysis*; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000633:toxicity*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D060766:Drinking Water; D009566:Nitrates; D014874:Water Pollutants, Chemical
keywords: Bladder cáncer; Case-control study; Drinking wáter; Nitrate; Water contaminants