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Ingested Nitrate, Disinfection By-products, and Kidney Cancer Risk in Older Women

Jones, Rena R.a; Weyer, Peter J.b; DellaValle, Curt T.a; Robien, Kimc; Cantor, Kenneth P.a; Krasner, Stuartd; Beane Freeman, Laura E.a; Ward, Mary H.a

doi: 10.1097/EDE.0000000000000647

Background: N-nitroso compounds formed endogenously after nitrate/nitrite ingestion are animal renal carcinogens. Previous epidemiologic studies of drinking water nitrate did not evaluate other potentially toxic water contaminants, including the suspected renal carcinogen chloroform.

Methods: In a cohort of postmenopausal women in Iowa (1986–2010), we used historical measurements to estimate long-term average concentrations of nitrate-nitrogen (NO3−N) and disinfection by-products (DBP) in public water supplies. For NO3–N and the regulated DBP (total trihalomethanes [THM] and the sum of five haloacetic acids [HAA5]), we estimated the number of years of exposure above one-half the current maximum contaminant level (>½-MCL NO3–N; >5 mg/L). Dietary intakes were assessed via food frequency questionnaire. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox models, and evaluated interactions with factors influencing N-nitroso compound formation.

Results: We identified 125 incident kidney cancers among 15,577 women reporting using water from public supplies >10 years. In multivariable models, risk was higher in the 95th percentile of average NO3–N (HRp95vsQ1 = 2.3; CI: 1.2, 4.3; Ptrend = 0.33) and for any years of exposure >½-MCL; adjustment for total THM did not materially change these associations. There were no independent relationships with total THM, individual THMs chloroform and bromodichloromethane, or with haloacetic acids. Dietary analyses yielded associations with high nitrite intake from processed meats but not nitrate or nitrite overall. We found no interactions.

Conclusions: Relatively high nitrate levels in public water supplies were associated with increased risk of renal cancer. Our results also suggest that nitrite from processed meat is a renal cancer risk factor.

From the aOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD; bCenter for Health Effects of Environmental Contamination, University of Iowa, Iowa City, IA; cDepartment of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington DC; and dMetropolitan Water District of Southern California, La Verne, CA.

Submitted 26 May 2016; accepted 28 February 2017.

This study was supported in part by the Intramural Research Program of the National Institutes of Health and by National Cancer Institute (NCI) extramural grant R01-CA39742. This study was approved by the Institutional Review Boards of the University of Minnesota and the University of Iowa and by the Office of Human Subjects Research at the NCI. Participants’ informed consent was implied by their returning the enrollment questionnaire.

The authors report no conflicts of interest.

Study data and code must be requested from the University of Minnesota and the National Cancer Institute and are subject to institutional data release policies.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (

Correspondence: Rena R. Jones, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room 6E124 Rockville, MD 20850. E-mail:

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