Association Between Anti-bacterial Drug Use and Digestive System Neoplasms: A Systematic Review and Meta-analysis

Background: Anti-bacterial drugs are thought to be associated with several malignancies. Objective: We conducted a systematic review and meta-analysis to assess the association between antibacterial drug exposure and the risk of digestive system neoplasms. Methods: Relevant publications reporting a relationship between antibiotic use and the risk of cancer were identified in PubMed, EMBASE, and Cochrane Central Register through June 2018. The random-effects model was selected to pool the risk ratios (RRs) and determine 95% confidence intervals (95% CIs). We performed subgroup analyses by tumor organ site, individual antibacterial drug class, and drug dose accumulation. Results: A total of 17 eligible studies (four randomized trials and 13 observational studies) involving 77,284 cancer patients were included in our analyses. Anti-bacterial drug exposure slightly increased the risk of overall digestive system cancer (RR, 1.12; 95% CI, 1.10-1.14), stomach and small intestine (RR, 1.12; 95% CI, 1.07-1.17), anorectocolonic (RR, 1.08; 95% CI, 1.05-1.12), and hepatobiliary and pancreatic cancers (RR, 1.18; 95% CI, 1.14-1.22). For different anti-bacterial drugs classes, nitroimidazoles (RR, 1.17; 95% CI, 1.09-1.26) and quinolones (RR, 1.18; 95% CI, 1.11-1.26) showed a modest association with the risk of cancers incidence. The risks of digestive system cancers increased with the rise of drug dose accumulation: low (RR, 1.08; 95% CI, 1.05-1.11), intermediate (RR, 1.15; 95% CI, 1.12-1.18), and high (RR, 1.22; 95% CI, 1.18-1.26). Conclusions: Anti-bacterial drug exposure was associated with the risks of digestive system cancer occurrence in our analysis.