A Systematic Review and Dose-Response Meta-Analysis of the Association Between Nitrate & Nitrite intake and Gastroesophageal Cancer Risk: A Study Protocol

ObjectivesThe global burden of cancer underscores the necessity for evidence-based strategies to identify and manage risk factors. Nitrate and nitrite are inherent byproducts resulting from microbial-mediated nitrogen oxidation in plants, soil, or water. Fruits, vegetables, and combinations thereof are integral constituents of a nutritious diet. Despite the potential carcinogenicity of N-nitroso compounds (NOCs), certain epidemiological investigations have reported a lack of correlation between the dietary intake of nitrate, nitrite, and NOCs and the occurrence of cancer in human subjects. MethodsPubMed/MEDLINE, Embase, WoS (Clarivate Analytics), Proquest, Scopus, and Google Scholar as electronic databases will be precisely searched for observational studies that assessed the relationship between nitrate/nitrite levels and gastric/esophageal cancer. In this study, an assessment will be conducted on studies spanning January 1, 1980, to October 30, 2023. The inclusion criteria will not restrict language. Discrepancies among the reviewers at various stages of the study, including screening, selection, quality assessment, and data extraction, will be resolved through consensus. In instances where disagreements persist unresolved, a third reviewer will decide. The combination method will be employed based on methodological similarities in the chosen articles, utilizing either the Random Effect Model or the Fixed Effect Model. Additionally, forest plots will be generated for the included articles. Statistical heterogeneity will be evaluated using the I2 statistic and the Q-statistic test. Furthermore, funnel plots will be employed to assess non-significant study effects and potential reporting bias. Eggers and Beggs tests will be executed, and the identification of publication bias will rely on significant findings (P < 0.05). ConclusionThe findings of this study should be of benefit to governments and researchers in maintaining safe levels of nitrate and nitrite in drinking water as well as preventing Gastroesophageal cancers.