Source-specific nitrate and nitrite intake and association with colorectal cancer in the Danish Diet, Cancer and Health Cohort

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 [HR_Q5vQ1 (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.