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Ingestion of Nitrate and Nitrite and Risk of Stomach Cancer in the NIH-AARP Diet and Health Study

Ward, Mary H.1; Kilfoy, Briseis1; Sinha, Rashmi1; Hollenbeck, A. R.2; Schatzkin, Arthur1; Cross, Amanda1

doi: 10.1097/01.ede.0000391997.79108.fb
Abstracts: ISEE 22nd Annual Conference, Seoul, Korea, 28 August–1 September 2010: Occupational and Environmental Cancer

1National Cancer Institute, Bethesda, MD; and 2AARP, Washington, DC.

Abstracts published in Epidemiology have been reviewed by the societies at whose meetings the abstracts have been accepted for presentation. These abstracts have not undergone review by the Editorial Board of Epidemiology.


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Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potent animal carcinogens. Ingestion of nitrate in the absence of nitrosation inhibitors (eg, vitamin C) increases endogenous nitrosation in humans. Few cohort studies have evaluated the joint effects of nitrate, nitrite, and nitrosation inhibitors.

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We evaluated intake of nitrate and nitrite in relation to stomach cancer incidence in the NIH-AARP Diet and Health Study, a cohort of 490,194 men and women 50–71 years of age. A total of 658 cases of stomach cancer were identified after 8 years of follow-up. We estimated dietary intake using a 124-item food frequency questionnaire and a database of nitrate and nitrite measurements from the published literature and from recent measurements of nitrite in meats. Potential exposure to nitrate from drinking water sources was determined by linking the census tract of the enrollment address to a United States Geological Survey regional model of nitrate levels in groundwater. Nitrate from drinking water sources was estimated to be low for the cohort; therefore, nitrate exposure estimates are based solely on dietary ingestion. We used Cox proportional hazards models to calculate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI).

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Overall, nitrate and nitrite ingestion were not associated with stomach cancer risk. Among those with low (<median) intake of vitamin C, we observed increasing stomach cancer risk with increasing ingestion of nitrate (highest vs. lowest quintile HR = 1.40; 95% CI: 0.97–2.01; P-trend = 0.056) and nitrite (HR = 1.52; 95% CI: 1.05–2.19; P-trend = 0.016). Processed meat sources of nitrite and nitrate were not associated with risk among those with either high or low vitamin C intake.

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Our results suggest that higher nitrate and nitrite ingestion in combination with lower vitamin C intake, a dietary pattern known to increase endogenous formation of NOC, increases the risk of stomach cancer.

© 2011 Lippincott Williams & Wilkins, Inc.