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Nitrate intake does not influence bladder cancer risk: The Netherlands Cohort Study

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Author: Zeegers, M.P. · Selen, R.F.M. · Kleinjans, J.C.S. · Goldbohm, R.A. · Brandt, P.A. van den
Institution: TNO Kwaliteit van Leven
Source:Environmental Health Perspectives, 10, 114, 1527-1531
Identifier: 239505
doi: doi:10.1289/ehp.9098
Keywords: Health · Food and Chemical Risk Analysis · Bladder cancer · Cohort study · Epidemiology · Etiology · Nitrate · alpha tocopherol · ascorbic acid · nitrate · tap water · adult · aged · article · bladder cancer · cancer incidence · cancer risk · chemical carcinogenesis · cigarette smoking · cohort analysis · confidence interval · controlled study · dietary intake · female · follow up · food analysis · food contamination · human · major clinical study · male · mathematical analysis · multivariate analysis · Netherlands · priority journal · proportional hazards model · questionnaire · risk assessment · risk factor · statistical significance · Aged · Carcinogens · Cohort Studies · Female · Humans · Male · Middle Aged · Multivariate Analysis · Netherlands · Nitrates · Risk Factors · Urinary Bladder Neoplasms


Objectives: N-nitroso compounds, endogenously formed from nitrate-derived nitrite, are suspected to be important bladder carcinogens. However, the association between nitrate exposure from food or drinking water and bladder cancer has not been substantially investigated in epidemiologic studies. Methods: We evaluated the associations between nitrate exposure and bladder cancer in the Netherlands Cohort Study, conducted among 120,852 men and women, 55-69 years of age at entry. Information on nitrate from diet was collected via a food frequency questionnaire in 1986 and a database on nitrate content of foods. Individual nitrate exposures from beverages prepared with tap water were calculated by linking the postal code of individual residence at baseline to water company data. After 9.3 years of follow-up and after excluding subjects with incomplete or inconsistent dietary data, 889 cases and 4,441 subcohort members were available for multivariate analyses. We calculated incidence rate ratios (RR) and corresponding 95% confidence intervals (CIs) using Cox regression analyses. We also evaluated possible effect modification of dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever). Results: The multivariate RRs for nitrate exposure from food, drinking water, and estimated total nitrate exposure were 1.06 (95% CI, 0,81-1,31), 1.06 (95% CI, 0.82-1.37), and 1.09 (95% CI, 0.84-1.42), respectively, comparing the highest to the lowest quintiles of intake. Dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever) had no significant impact on these results. Conclusion: Although the association between nitrate exposure and bladder cancer risk is biologically plausible, our results in this study do not support an association between nitrate exposure and bladder cancer risk.