Nitrate and nitrite intake and risk of colorectal cancer: a population-based cohort study

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Abstract
Background: Dietary nitrate exposure originates from vegetables and drinking water, and is, together with nitrite, used as food additives in animal products. Both compounds can generate N-nitroso compounds, some of which are known animal carcinogens. However, epidemiological evidence regarding nitrate and nitrite intake in relation to colorectal cancer (CRC) risk and its subsites remains limited. Methods: Nitrate and nitrite intake was assessed by linking a food and drinking water database to food frequency questionnaires completed in 1997 and updated in 2009 and 2019, by 82 009 middle-aged to elderly men and women of 2 population-based cohorts from the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research. We ascertained incident CRC through the Swedish Cancer Registry from 1998 to 2022. Cox proportional hazards models were fitted to evaluate exposure-outcome associations, presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: We ascertained 3170 CRC cases. No associations were observed for nitrate intake with CRC. In contrast, when comparing the highest with the lowest quintile, nitrite intake was associated with a dose-dependent higher risk of CRC in men (HR 1.23; 95% CI = 1.06 to 1.43; Ptrend < .05) but not in women. CRC subsite analyses in men indicated the strongest association for distal colon cancer (HR 1.50; 95% CI = 1.13 to 1.98). Conclusion: A higher nitrite intake was associated with a higher CRC risk in men, particularly distal colon cancer. These findings indicate potential sex differences and differential susceptibilities across the colorectum in nitrite-related cancer risk.
Funding Information
  • Vetenskapsrådet (2025-02373)

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