Nitrate is a drinking water contaminant arising from agricultural sources and a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens.
To investigate the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women.
We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) >10 years (N=15,577), we estimated average nitrate (NO3-N) and total trihalomethanes (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5mg/L, TTHM: 40µg/mL) from historical monitoring data. We computed hazard ratios (HR) and 95% confidence intervals (CI), and assessed nitrate interactions with TTHM and modifiers of NOC formation (smoking, vitamin C).
We identified 258 bladder cancer cases, including 130 among women >10 years at their PWS. In multivariable-adjusted models, we observed non-significant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR=1.48;CI=0.92,2.40;ptrend=0.11), and significant associations among those exposed ≥4 years to drinking water with >5mg/L NO3-N (HR=1.62;CI=1.06,2.47;ptrend=0.03) compared to women with no years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR=3.67;95% CI=1.43,9.38 and HR=3.48; 95% CI=1.20,10.06 for average water NO3-N and ≥4 years >5mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer.
Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women.
Environmental health perspectives. 2016 Jun 03 [Epub ahead of print]
Rena R Jones, Peter J Weyer, Curt T Dellavalle, Maki Inoue-Choi, Kristin E Anderson, Kenneth P Cantor, Stuart Krasner, Kim Robien, Laura E Beane Freeman, Debra T Silverman, Mary H Ward
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA., Center for Health Effects of Environmental Contamination, University of Iowa, Coralville, Iowa, USA., Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA., Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA., Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA., Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA., Metropolitan Water District of Southern California, La Verne, California, USA., Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, USA., Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA., Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA., Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.