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Journal Article

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Environmental Health Perspectives


BACKGROUND: 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.

OBJECTIVES: To investigate the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women.


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