Nitrate-nitrite Exposure Through Drinking Water and Diet and Risk of Colorectal Cancer: A Systematic Review and Meta-analysis of Observational Studies

Background: Considerable controversy exists regarding the association between nitrate intake and risk of colorectal cancer. Therefore, we performed a dose-response meta-analysis of observational studies.

Methods: We identified relevant studies by searching PubMed, Scopus and ISI Web of Knowledge until April 2020 and references of retrieved relevant articles. The random-effects model was used to calculate pooled effect size (ESs) and 95% confidence intervals (CIs).

Results: Fifteen prospective cohort and case-control papers were included in this systematic review and meta-analysis. In total, 2,573,524 participants with an age range between 20 and 85 years were included. The total number of colorectal cancer cases was 38,848. Intake of nitrate from diet was associated with a risk of colorectal cancer (Pooled HR: 1.13; 95% CI: 1.04-1.23, I = 38%; P = 0.08). Nitrite in diet was not significantly associated with risk of colorectal cancer (pooled HR: 1.07; 95% CI: 0.95-1.21, I = 61.6%; P = 0.005). Nitrate in water did not show an association with risk of colorectal cancer (pooled HR: 1.04; 95% CI: 0.92-1.19, I = 64.7%; P = 0.002). Non-linear dose-response analysis revealed no significant association of dietary nitrite and also nitrate of drinking water with risk of colorectal cancer. However, dietary nitrate was marginally associated with a greater risk of colorectal cancer. Linear dose-response analysis of nitrate from diet was not associated with colorectal cancer risk by an additional 50 mg per day. Such a non-significant association was also seen for colorectal cancer risk by an additional 1 mg per day and 1 mg/l from dietary nitrite and water nitrate respectively.

Conclusions: Dietary nitrate was related to a higher risk of colorectal cancer risk. However, intake of nitrite from diet and nitrate from the drinking water was not associated with colorectal cancer risk.