Nitrate in drinking water and bladder cancer risk in Spain

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. 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. Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤5mg/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. ≤4mg/day. Adjustment for several covariables showed similar results to crude analyses. 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. •Long-term residential and ingested nitrate levels in drinking water were estimated.•Mean residential levels ranged from 2.1mg/L to 12.0mg/L among regions.•Higher risk suggested only for subjects with highest residential levels.•Protective ORs with ingested nitrate may be confounded by water intake.•Endogenous nitrosation factors (e.g. vitamin C intake) did not modify the results.