296 Antibiotic Use and Risk of Colorectal Neoplasia: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: Colorectal cancer (CRC) is the third most prevalent cancer and the third leading cause of cancer death for women and men in the United States. There is emerging evidence that the gut microbiome plays a role in CRC development, and antibiotics are one of the most common exposures that can alter the gut microbiome. We performed a systematic review and meta-analysis to characterize the association between antibiotic use and colorectal neoplasia risk. METHODS: We searched Pubmed, EMBASE, and Web of Science for articles describing the relationship between antibiotic exposure and colorectal neoplasia (cancer or adenoma) through October 2018. A total of 5342 citations were identified, which were reviewed independently by two investigators. After screening, we evaluated 15 articles and included 5 in the final analysis. We assessed the association between any antibiotic use as well as intensity of antibiotic use (defined as number of courses or duration of therapy) and colorectal neoplasia risk. Random effects meta-analysis was performed. RESULTS: Four studies provided five estimates for the association between any antibiotic use and risk of colorectal neoplasia. There was a 4% increased risk of neoplasia among individuals exposed to antibiotics (RR 1.04, 95% CI 1.02–1.07, Figure 1), with no evidence of heterogeneity (P = 0.96, I2 = 0%). Five studies provided 13 estimates of the association between antibiotic intensity and colorectal neoplasia. Individuals with the highest intensity of antibiotic exposure had a 13% higher risk of colorectal neoplasia than those with lowest exposure (RR 1.13, 95% CI 1.06–1.21, Figure 2). However, significant heterogeneity was observed (P = 0.04, I2 = 45%). Given the small number of studies, sub-group analyses on antibiotic class could not be performed. CONCLUSION: Antibiotic exposure is associated with a subsequent increased risk of colorectal neoplasia. Furthermore, this relationship appears to be dose-dependent. Given the widespread use of antibiotics in childhood and early adulthood, additional research to further characterize this relationship is needed.