Consumption of nitrate, nitrite, and nitrosodimethylamine and the risk of upper aerodigestive tract cancer

Evidence from animal studies indicates that various N-nitroso compounds are carcinogenic. We investigated whether consumption of foods and beverages containing nitrosodimethylamine, nitrites, and nitrates affected the risk of laryngeal, esophageal, and oral cancer. In a population-based case-control study in western Washington state, dietary consumption of these substances was measured in 645 cases (169 laryngeal, 125 esophageal, and 351 oral) and 458 controls. After adjustment for tobacco, alcohol, and other known risk factors, there was a 52% reduction in the risk of upper aerodigestive tract cancer for individuals who consumed higher amounts of nitrate (upper tertile) compared with the lowest tertile (P < 0.001 for trend). Nitrate intake was associated with a reduction in cancer risk at all three sites. The reduction in the risk of esophageal cancer with increasing nitrate consumption was more evident in frequent tea drinkers than in other subjects. There was no significant association between nitrite consumption and the risk of laryngeal or oral cancer. However, for individuals with a history of canker sores (an indicator of possible endogenous nitrosation), the risk of esophageal cancer was seven times greater in those with high versus low nitrite intake. Consumption of foods high in nitrosodimethylamine was associated with a 79% increased risk of upper aerodigestive tract cancer (P = 0.037 for trend). Cases consumed smoked fish more frequently than did controls [odds ratio (OR) = 3.03]. Daily intake of beer and of nitrite-containing meats were associated with an increased esophageal cancer risk (OR = 2.48 and 1.82, respectively).