Author Identifier (ORCID)
Nicola P. Bondonno's ORCID record 
Pratik Pokharel's ORCID record
Abstract
Introduction: Nitrate and nitrite, present in food and drinking water, may contribute to colorectal cancer (CRC) through the formation of carcinogenic N-nitroso compounds (NOCs). This study examined source-specific associations with CRC and subtypes, considering potential dietary and lifestyle factors that influence NOC formation. Methods: In the Danish Diet, Cancer, and Health Cohort (N=54,610), nitrate/nitrite intake was estimated from comprehensive databases and national monitoring data. Over 27 years, 2245 CRC cases (1508 colon and 737 rectal) were identified via the Danish Cancer Registry. Cox proportional hazards models adjusted for sociodemographic, diet, and lifestyle factors were used to examine associations, with stratified analyses by sex and factors influencing NOC formation. Results: No associations were found between nitrate/nitrite intakes from plant, naturally-occurring animal sources, or additive-permitted meat sources and CRC. However, higher nitrate intake from tap water (mg/d) was associated with a higher rate of distal colon cancer [HRQ5vQ1 (95% CI); 1.48 (1.11, 1.97)], though not CRC overall. A nitrate concentration in tap water ≥9.25 mg/L was linked to a higher colon cancer rate [HR 1.52 (1.11, 2.07)] compared to < 1.27 mg/L. This association appeared stronger in individuals with risk-promoting factors (smoking and high red meat intake) and weaker among those with a high intake of NOC inhibiting factors (vitamin C, vitamin E, folate, and flavonoids). Conclusion: Nitrate/nitrite intakes from food sources were not associated with rate of CRC in the cohort, but tap water nitrate, at higher intake levels and at concentrations over ≥9.25 mg/L were linked to higher rates of distal colon and colon cancer, respectively.
Keywords
Dietary nitrate, drinking water, colorectal cancer, diet, cohort, nitrite
Document Type
Journal Article
Date of Publication
6-10-2025
Article Number
109658
Publication Title
Environment International
Publisher
Elsevier
School
Nutrition and Health Innovation Research Institute / School of Medical and Health Sciences
RAS ID
83423
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 Royal Perth Hospital Research Foundation ‘Lawrie Beilin’ Career Advancement Fellowship (ID: CAF 127/2020) and the Western Australian Future Health Research and Innovation Fund. The salary of JMH is supported by a National Health and Medical Research Council of Australia Senior Research Fellowship, Australia (Grant number APP1116937).
Funding received from the National Health and Medical Research Council (NHMRC)
APP1159914, APP1116937
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Recommended Citation
Erichsen, D. W., Bondonno, N. P., Pokharel, P., Rosthøj, S., Bondonno, C. P., Zhong, L., Schullehner, J., Sigsgaard, T., Hendriksen, P. F., Dalgaard, F., Raaschou-Nielsen, O., Hodgson, J. M., Dahm, C. C., Olsen, A., Tjønneland, A., & Kyrø, C. (2025). Source-specific nitrate and nitrite intake and association with colorectal cancer in the Danish Diet, Cancer and Health Cohort. Environment International, 202, Article 109658. https://doi.org/10.1016/j.envint.2025.109658