Source-specific nitrate and nitrite intake and associations with gastric cancer in the Danish Diet, Cancer and Health Cohort.

UNLABELLED: Nitrate and nitrite, present in foods and drinking water, may contribute to gastric cancer (GC) through the formation of carcinogenic N-nitrosamines, but risks likely vary by source and endogenous nitrosating factors. In the Danish Diet, Cancer, and Health Cohort, source-specific nitrate and nitrite intakes (plant sources, naturally-occurring animal sources, additive-permitted meat sources, and drinking water) were estimated from a food frequency questionnaire using food databases and water monitoring data. Associations with GC, identified via the Danish Cancer Registry, were examined using multivariable-adjusted Cox proportional hazards models. Analyses were stratified by GC risk factors and factors hypothesized to influence endogenous N-nitrosamine formation to explore potential effect modification. Among 54,610 participants, 260 incident cases of GC (120 cardia, 59 non-cardia, and 81 overlapping/unclassified) were identified over 27 years. Plant sourced nitrite intake was associated with lower GC rates [HRQ5vQ1 (95%CI): 0.63 (0.41, 0.96)]. Conversely, intakes of nitrite from naturally-occurring animal sources [HRQ4vQ1 1.55 (1.01, 2.38)]; and both nitrate and nitrite from additive-permitted meat sources were associated with higher rates of GC [HRQ5vQ1 3.12 (1.09, 8.88) and 1.94 (1.19, 3.15), respectively], with higher point estimates for non-cardia GC. Nitrate from tap water was associated with higher rates of cardia GC rates [HRQ5vsQ1 1.95 (1.11, 3.43)]. Nitrate and nitrite intakes demonstrated heterogeneous associations with GC incidence according to source and anatomical subsite. These findings warrant the re-evaluation of legislation on nitrate and nitrite additives in processed meats and threshold levels for nitrate in drinking water, as well as further investigation into nitrite from animal-sourced foods.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-026-01390-6.