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

Dietary nitrate exposure originates from vegetables, 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.

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 two 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).

We ascertained 3,170 CRC cases. No associations were observed for nitrate intake with CRC. In contrast, when comparing the highest to the lowest quintile, nitrite intake was associated with a dose-dependent higher risk of CRC in men (HR 1.23; 95%CI 1.06-1.43; p-trend<0.05) but not in women. CRC subsite analyses in men indicated the strongest association for distal colon cancer (HR 1.50; 95% CI: 1.13-1.98).

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.