Chronic exposure to nitrate in drinking water and the risk of bladder cancer: a meta-analysis of epidemiological evidence

Objective: This study aimed to assess the association between chronic exposure to nitrate in drinking water and the risk of bladder cancer. Study design: Meta-analysis. Methods: After a systematic retrieval of eligible epidemiological studies, pooled odds ratios (ORs) with 95% confidence intervals (CIs) of bladder cancer for people in the highest vs the lowest categories of nitrate exposure were calculated using the fixed- or random-effects model. We conducted two separate meta-analyses, one considering nitrate exposure as nitrate concentration in drinking water and the other one as daily nitrate intake from drinking water. Results: A total of five studies (three case–control and two cohort studies) were included. The pooled OR (95% CI) of bladder cancer for the highest vs the lowest category of nitrate concentration in drinking water was 0.98 (0.60, 1.57), and daily nitrate intake from drinking water was 1.00 (0.69, 1.45). Both meta-analyses showed high heterogeneity across studies (I2 = 80.8% and 65.0%, respectively). Removing studies with the high risk of bias increased the risk and reduced the heterogeneity: [(nitrate concentration in drinking water: 1.36 (1.03, 1.79), I2 = 0.0%) and (daily nitrate intake from drinking water: 1.14 (0.90, 1.46), I2 = 8.4%)]. Conclusion: The current epidemiological evidence failed to establish a conclusive relationship between chronic exposure to nitrate in drinking water and the risk of bladder cancer. While no association and high heterogeneity across studies were detected in the two meta-analyses, removing studies with the high risk of bias increased the risk and dissolved the heterogeneity.