Endogenous formation of N-nitrosodimethylamine (NDMA) from dietary nitrite and nitrate intake and its association with cancer risk.

[OBJECTIVE] Nitrites and nitrates can undergo endogenous nitrosation to form nitrosamine in the human body. The association between nitrosation and cancer risk remains unclear.

[METHOD] Individuals from the UK Biobank cohort who participated in the 24-h dietary assessment were included in this study. A physiologically based pharmacokinetic (PBPK) model was used to estimate the metabolic conversion of dietary nitrite and nitrate, with NDMA selected as the representative nitrosamine. The cancer risks were assessed using Cox proportional hazards regression.

[RESULTS] During the 12 years follow-up period, a total of 27,438 incident cancer cases were identified. Compared to participants in the lowest NDMA exposure range (<0.033 μg/day), those in the highest category (>0.044 μg/day) had a 4% higher risk of overall cancer (95% CI: 1.01-1.08) and a 12% higher risk of colorectal cancer (95% CI: 1.00-1.26). Additionally, the combination of being overweight and having high NDMA exposure was significantly associated with an increased cancer risk (Ptrend = 0.001).

[CONCLUSION] Elevated nitrosamines derived from dietary nitrite and nitrate increase the risk of overall cancer and colorectal cancer. Enhanced monitoring and attention of factors that promote nitrosation are essential, especially in high-risk populations.