Association of Dietary Nitrate, Nitrite, and N-Nitroso Compounds Intake and Gastrointestinal Cancers: A Systematic Review and Meta-Analysis

Abstract

N-nitroso compounds (NOCs) are a class of chemical carcinogens found in various environmental sources such as food, drinking water, cigarette smoke, the work environment, and the indoor air population. We conducted a systematic review and meta-analysis to investigate the links between nitrate, nitrite, and NOCs in food and water and the risk of gastrointestinal (GI) cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC). A systematic search of the literature in Scopus, PubMed, Google Scholar, Web of Science, ScienceDirect, and Embase was performed for studies on the association between NOCs in drinking water and food sources and GI cancers. Forest plots of relative risk (RR) were constructed for all the cancer sites and the intake sources. The random-effects model was used to assess the heterogeneity between studies. Forty articles were included after removing duplicate and irrelevant articles. The meta-analysis indicated that the intake of high dose vs. low dose of these compounds was significantly associated with the overall GI cancer risk and nitrite (RR = 1.18, 95% CI = 1.07–1.29), and N-nitrosodimethylamine (NDMA) (RR = 1.32, 95% CI = 1.06–1.65). We found that dietary nitrite intake increased GC (RR = 1.33, 95% CI = 1.02–1.73), and EC (RR = 1.38, 95% CI = 1.01–1.89). Additionally, dietary NDMA intake increased the risk of CRC (RR = 1.36, 95% CI = 1.18–1.58). This meta-analysis provides some evidence that the intake of dietary and water nitrate, nitrite, and NOCs may be associated with GI cancers. In particular, dietary nitrite is linked to GC and EC risks and dietary NDMA intake is associated with CRC.