Abstract

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 [HRlog (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.

Keywords

bladder cancer, cohort, diet, drinking water, nitrate, nitrite

Document Type

Journal Article

Date of Publication

8-1-2026

Article Number

110387

ISSN

01604120

Volume

214

Publication Title

Environment International

Publisher

Elsevier

School

Nutrition and Health Innovation Research Institute / School of Medical and Health Sciences

Funding Information

The Danish Diet, Cancer, and Health Cohort was funded by the Danish Cancer Society, Denmark. This study was supported by grants from the World Cancer Research Fund (IIG_FULL_2020_020) and Independent Research Fund Denmark (1030-00307B). Funding for grant IIG_FULL_2020_020 was obtained from Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme. The study was supported by BERTHA – the Danish Big Data Centre for Environment and Health funded by the Novo Nordisk Foundation Challenge Programme (grant NNF17OC0027864). NPB is funded by a National Health and Medical Research Council Early Career Fellowship (Grant number APP1159914), Australia. The salary of CPB is supported by a National Health and Medical Research Council Ideas Grant (Grant number APP2030071) and Western Australian Future Health Research and Innovation Fund (Grant number WANMA/EL2023-24/2). The salary of JMH is supported by a National Health and Medical Research Council of Australia Senior Research Fellowship, Australia (Grant number APP1116937). The salary of JS is supported by the European Union Horizon Europe project MARCHES (grant no 101095430).

Funding received from the National Health and Medical Research Council (NHMRC)

APP1159914, APP2030071, APP1116937

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Recommended Citation

Erichsen, D. W., Kyrø, C., Schullehner, J., Rosthøj, S., Bondonno, C. P., Zhong, L., Raaschou-Nielsen, O., Pokharel, P., Sigsgaard, T., Hendriksen, P. F., Dalgaard, F., Dahl, C., Hodgson, J. M., Dahm, C. C., Olsen, A., Tjønneland, A., & Bondonno, N. P. (2026). Source-specific nitrate and nitrite intake and bladder cancer: Findings from the Danish Diet, Cancer and Health Cohort. Environment International, 214, Article 110387. https://doi.org/10.1016/j.envint.2026.110387

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Link to publisher version (DOI)

10.1016/j.envint.2026.110387