Ingestion of nitrate and nitrite from drinking water and diet and cancers of the gastrointestinal tract in Iowa women

Abstract

Background: Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potent animal carcinogens in the gastrointestinal tract. Methods: We evaluated nitrate ingestion from public drinking water supplies (PWS), private well use, and dietary nitrate and nitrite intakes in relation to incidence (through 2014) of cancers of the esophagus (n=37), stomach (97), small intestine (47), liver (56), and gallbladder (66) in the Iowa Women’s Health Study (42,000 women ages 50-75 in 1986). Historical nitrate measurements from PWS were linked to the enrollment address by duration. We computed average concentrations and number of years >5 mg/L NO3-N (½ the maximum contaminant level [MCL]). Dietary nitrate and nitrite were estimated using a food frequency questionnaire. We used Cox proportional hazards models to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: In adjusted models, liver cancer risk was elevated among private well users (HR=2.5, CI 0.8-8.5) and those with any years >5 mg/L NO3-N (HR=2.0, CI 0.8-4.9); there was no association with average concentrations (HRper1mg/L NO3-N =1.1, CI 0.7-1.7). Private well use and PWS nitrate concentrations were not associated with other cancers. Dietary nitrate and nitrite from plants was inversely associated with small intestine (HRQ4vsQ1=0.4, CI 0.1-0.9) and gall bladder cancer (HRQ4vsQ1=0.3, CI 0.1-0.8), respectively; there were no associations for the other cancers. Nitrite intake from processed meats was associated with increased risk of stomach (HRnitriteQ4vsQ1=1.7, CI 1.0-3.0) and elevated risk of liver cancer (HRnitriteQ4vsQ1=1.8, CI 0.8-4.0) but was inversely associated with small intestine cancer (HRnitriteQ4vsQ1=0.4, CI 0.1-1.0). Power was limited, but there was no evidence for effect modification by vitamin C and red meat, factors affecting nitrosation. Conclusion: We found novel suggestive evidence that private well use and PWS nitrate may increase liver cancer risk. These associations should be evaluated in studies with larger case numbers.