A systematic review and dose‒response meta-analysis of the association between nitrate & nitrite intake and gastroesophageal cancer risk

Objective

The objective of this systematic review and dose‒response meta-analysis was to assess the associations between the dietary consumption of nitrate and nitrite and the risk of gastric and esophageal cancer.

Methods

MEDLINE, Scopus, Embase, Web of Science, Proquest, and Google Scholar were searched until April 1, 2024. Articles were selected by two independent researchers on the basis of the inclusion and exclusion criteria. Data regarding the study design, type of exposure and outcomes, intervals of intake of nitrate or nitrite in each layer, OR/RR/HR of the relationship for each layer of intake, total sample size, and number of cases of gastric or esophageal cancer were extracted. The certainty of the evidence was rated via the GRADE method. The pooled odds ratios, risk ratios, and dose‒response analyses were calculated via Stata version 17.0. The best-fit dose‒response model was assessed by the P value for linearity and nonlinearity. Study heterogeneity was assessed via the I² and Q tests.

Results

We found 2124 nonredundant studies, 234 of which were potentially relevant. Eighteen articles met the inclusion criteria and were included in the review. The results of the meta-analysis revealed a significant positive association between nitrite intake and gastric cancer in both case‒control studies (OR = 1.29, 95 % CI = 1.09–1.52, P value = 0.001, I² = 1.91 %) and cohort studies (RR = 1.17, 95 % CI = 1.00–1.37, P value = 0.04, I² = 0.00 %). In addition, case‒control studies revealed a nonsignificant inverse association between nitrate intake and gastric cancer incidence (OR = 0.71, 95 % CI = 0.50–1.01, P value = 0.06, I² = 74.89 %), and cohort studies (RR = 0.89, 95 % CI = 0.73–1.09, P value = 0.27, I² = 0.00 %). Case‒control studies also revealed no significant correlation between nitrite intake and esophageal cancer incidence (OR = 1.48, 95 % CI = 0.91 to 2.42, P value = 0.12, I² = 0.001 %). Nitrites correlated linearly with gastric cancer (linearity P value = 0.001). The most appropriate fit models for the relationship between nitrate and gastric cancer were both piecewise linear and natural polynomial regression (quadratic) models (P values = 0.003 and 0.005, respectively). There was no significant publication bias.

Conclusion

According to this meta-analysis, high consumption of nitrites was associated with an increased risk of gastric cancer in case‒control and cohort studies with a linear regression model, and dietary nitrate intake was not associated with the risk of gastric cancer in either case‒control or cohort studies. These findings are inconclusive and require confirmation in future prospective studies with robust methodologies and adjustments for potential confounders.