Association Between Dietary Nitrite intake and Glioma Risk: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies

Background: Nitrite and nitrate intake through food and water may be an important risk factor for many cancers, including glioma. However, the association of nitrite and nitrate with glioma is unclear. Objective: This review aimed to quantitatively assess the effects of nitrite and nitrate on glioma by meta-analysis. Methods: A literature search was conducted for available articles published in English using the databases of Embase, Web of Science, PubMed, Medline, and the Cochrane Library up to 24 March 2022. According to heterogeneity, the fixed-effects or random-effects model was selected to obtain the merger's relative risk (RR). Based on the methods described by Greenland and Longnecker, we explored the dose-response relationship between nitrite/nitrate and the risk of glioma. Subgroup analysis, sensitivity analysis, and publication bias tests were also used. Results: This study reviewed 17 articles, including 812,107 participants and 4,574 cases. For glioma in adults, compared with the lowest intakes, the highest intakes of nitrite significantly increased the risk of glioma (RR=1.26, 95% confidence interval (95%CI):1.09-1.47). For brain tumors in children, compared with the lowest intakes, the highest intakes of nitrate significantly increased the risk of brain tumors (RR=1.27, 95%CI:1.06-1.52). The results of subgroup and sensitivity analyses remained unchanged. In the dose-response relationship, per 1 mg/day increase in nitrite intake increased the risk of glioma by 14% (RR=1.14, 95%CI:1.01-1.27). Conclusions: Our analysis suggests that nitrite increases the risk of glioma in adults, while nitrate increases the risk of brain tumors in children. Therefore, the effects of nitrite and nitrate on glioma cannot be ignored.