Nitrate in public water supplies and the risk of renal cell carcinoma

Drinking water and dietary sources of nitrate and nitrite can react in vivo with amines and amides to form N-nitroso compounds (NOC), potent animal carcinogens. Nitrate is a widespread contaminant of drinking water supplies especially in agricultural areas. We conducted a population-based case–control study of renal cell carcinoma in 1986–1989 in Iowa, a state with elevated levels in many public water supplies. We collected a lifetime water source history, but due to limited monitoring data, most analyses focused on the subpopulation, who used Iowa public supplies with nitrate measurements (actual or imputed data) for ≥70% of their person-years since 1960 (201 cases, 1,244 controls). We computed the average nitrate level and years using a public supply with nitrate levels >5 and >10 mg/l. Dietary nitrate and nitrite were estimated from a 55-item food frequency questionnaire. There was no association of renal cell carcinoma with the average nitrate level and years using public supplies >5 and >10 mg/l nitrate-nitrogen (10+ years >5 mg/l odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.66, 1.60). However, higher nitrate exposure was associated with an increased risk among subgroups with above the median red meat intake (10+ years >5 mg/l OR = 1.91, 95% CI 1.04–3.51) or below the median vitamin C intake (10+ years >5 mg/l OR = 1.90, 95% CI 1.01, 3.56), dietary factors that increase the endogenous formation of NOC. Exclusion of long-term Des Moines residents, a large proportion of the high exposure categories, attenuated the association. These findings deserve additional study in populations with high water nitrate intake and information on dietary intakes.