Ingestion of Nitrate and Nitrite and Risk of Stomach and Other Digestive System Cancers in the Iowa Women’s Health Study

Abstract

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC) which are potent animal carcinogens for the organs of the digestive system. We evaluated dietary intakes of nitrate and nitrite, as well as nitrate ingestion from drinking water (public drinking water supplies (PWS)), in relation to the incidence (1986–2014) of cancers of the esophagus (n = 36), stomach (n = 84), small intestine (n = 32), liver (n = 31), gallbladder (n = 66), and bile duct (n = 58) in the Iowa Women’s Health Study (42,000 women aged from 50 to 75 in 1986). Dietary nitrate and nitrite were estimated using a food frequency questionnaire and a database of nitrate and nitrite levels in foods. Historical nitrate measurements from PWS were linked to the enrollment address by duration. We used Cox regression to compute hazard ratios (HR) and 95% confidence intervals (CI) for exposure quartiles (Q), tertiles (T), or medians, depending on the number of cancer cases. In adjusted models, nitrite intake from processed meats was associated with an increased risk of stomach cancer (HRQ4vsQ1 = 2.2, CI: 1.2–4.3). A high intake of total dietary nitrite was inversely associated with gallbladder cancer (HRQ4vsQ1 = 0.3, CI: 0.1–0.96), driven by an inverse association with plant sources of nitrite (HRQ4vsQ1 = 0.3, CI: 0.1–0.9). Additionally, small intestine cancer was inversely associated with a high intake of animal nitrite (HRT3vsT1 = 0.2, CI: 0.1–0.7). There were no other dietary associations. Nitrate concentrations in PWS (average, years ≥ 1/2 the maximum contaminant level) were not associated with cancer incidence. Our findings for stomach cancer are consistent with prior dietary studies, and we are the first to evaluate nitrate and nitrite ingestion for certain gastrointestinal cancers.

Diet and carcinogenesis of gastric cancer

“…The Iowa Women's study is a prospective study of 42 000 women followed via food questionnaires since 1986. Consistent with previous reports, they recently reported an increased risk of gastric cancer in adjusted models with high nitrite intake from processed meats [hazard ratio 2.2, 95% confidence interval (CI) 1.2–4.3] [5 ▪ ]. In a meta-analysis that included 232 studies with over 33 million participants, red meat intake more than four times a week increased the odds of developing gastric cancer, although the results were not statistically significant [odds ratio (OR) of 1.31, 95% CI 0.87–1.96) [6].…”

Bionic Enzyme-Assisted Ion-Selective Amperometric Biosensor Based on 3D Porous Conductive Matrix for Point-of-Care Nitrite Testing

“…Stomach cancer is the fourth leading cause of cancer deaths worldwide, where the rate of median survival is less than 12 months for the advanced stage . One of the biological causes of stomach cancer is the chronic elevation of blood nitrite level caused by abnormal metabolism, which gradually leads to the accumulation of endogenous N-nitroso compounds . Besides, a lasting high nitrite level in the human body can also cause other severe diseases including anemia, lactic acidosis, spontaneous abortion, and blue baby syndrome .…”

“…1 One of the biological causes of stomach cancer is the chronic elevation of blood nitrite level caused by abnormal metabolism, which gradually leads to the accumulation of endogenous N-nitroso compounds. 2 Besides, a lasting high nitrite level in the human body can also cause other severe diseases including anemia, lactic acidosis, 3 spontaneous abortion, and blue baby syndrome. 4 However, for nitrite, less is not always better.…”

Microalgae-Based Biotechnology as Alternative Biofertilizers for Soil Enhancement and Carbon Footprint Reduction: Advantages and Implications

“…A study by Buller et al [ 66 ] in Iowa evaluated the dietary intake of nitrates and nitrites in women between 50–75 years old, both by the consumption of vegetables and by water with high concentrations, concerning the incidence (1986–2014) of esophageal cancers ( n = 36), stomach ( n = 84), small intestine ( n = 32), liver ( n = 31), gallbladder ( n = 66), and bile duct ( n = 58); in their models, they found an association between meat nitrates processed where the consumers generated some stomach cancer, just as consumption of total dietary nitrite from vegetable sources is inversely associated with gallbladder cancer; in addition, small intestine cancer was related to a high intake of animal nitrite.…”