Nadia Espejo-Herrera1, Kenneth P Cantor2, Nuria Malats3, Debra T Silverman2, Adonina Tardón4, Reina García-Closas5, Consol Serra6, Manolis Kogevinas7, Cristina M Villanueva8. 1. 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. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. 3. Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. 4. Universidad de Oviedo, Oviedo, Spain. 5. Hospital Universitario de Canarias, La Laguna, Spain. 6. Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, Spain; Consorci Hospitalari Parc Taulí, Sabadell, Spain. 7. 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. 8. 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.
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. CONCLUSION: 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.
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. CONCLUSION: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.
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