Nitrate-nitrite exposure through drinking water and diet and risk of colorectal cancer: A systematic review and meta-analysis of observational studies

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. 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). 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, I2 = 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, I2 = 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, I2 = 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. 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.