Source-specific nitrate and nitrite intake and bladder cancer: findings from the Danish Diet, Cancer and Health Cohort

Introduction Nitrate and nitrite, present in ground and drinking water, as well as foods, may contribute to bladder cancer through the formation of carcinogenic N -nitrosamines. However, risk likely depends on both the source and endogenous nitrosating factors. Methods Among participants of the Danish Diet, Cancer, and Health Cohort (N = 54,610) with no history of cancer, source-specific nitrate and nitrite intakes (drinking water, plant sources, naturally occurring animal sources, and additive-permitted meat sources) were estimated from national water monitoring data and food frequency questionnaires using food databases. Bladder cancer cases were ascertained through the Danish Cancer Registry. Multivariable-adjusted Cox proportional hazards models were used to examine associations, and analyses were stratified by established bladder cancer risk factors and factors hypothesized to influence endogenous N -nitrosamine formation to explore potential effect modification. Results During 27 years of follow-up, 1,058 bladder cancer cases were identified. No associations were observed for nitrate intake [HR_log (95% CI) per doubling of intake (mg/d): drinking water: 0.88 (0.73, 1.08), plant sources: 0.91 (0.74, 1.12), naturally occurring animal sources: 0.83 (0.67, 1.02), additive permitted meat sources 1.06 (0.84, 1.32)]. Similar estimates were observed for source-specific nitrite intakes. Associations did not appear to be modified by bladder cancer risk factors or endogenous nitrosating factors. Conclusion The lack of associations between nitrate and nitrite exposure and bladder cancer may reflect either a true absence of effect or exposure levels that are too low be biologically relevant for bladder carcinogenesis. Future studies in populations with higher exposure levels are warranted.