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Epidemiology. 2019 Sep 30. doi: 10.1097/EDE.0000000000001112. [Epub ahead of print]

Ingested nitrate and nitrite and bladder cancer in Northern New England.

Author information

1
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
2
Department of Epidemiology and Public Health, University of Maryland School of Medicine, and Program in Oncology, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD.
3
Department of Biostatistics, Virginia Commonwealth University, Richmond, VA.
4
Vermont Department of Health, Burlington, VT.
5
Bureau of Public Health Statistics and Informatics, Department of Health and Human Services, Concord, NH.
6
Maine Cancer Registry, Augusta, ME.
7
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
8
Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
9
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH.

Abstract

BACKGROUND:

N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study.

METHODS:

Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N ) and average daily nitrate intake (mg/day) from 1970 to diagnosis/reference date (987 cases and 1180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1037 cases and 1225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and water intake.

RESULTS:

Average drinking water nitrate concentration above the 95 percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR=1.5, 95% CI: 0.97-2.3; p-trend=0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest vs. lowest quintile OR for nitrate=1.4, 95% CI: 1.0-2.0; p-trend=0.04; OR for nitrite=1.5, 95% CI: 1.0-2.1; p-trend=0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (p-interaction 0.05) and processed red meat (0.07).

CONCLUSIONS:

Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

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