The Relation Between Antibiotic Use and Gastrointestinal Cancer: A Systematic Review and Meta-Analysis

Cancer remains a major cause of premature mortality worldwide, with incidence and mortality rates continuing to rise. Antibiotic use, while essential for treating infections, has been linked to an increased risk of certain cancers, particularly colorectal cancer (CRC), possibly through microbiome disruption. Although previous studies and meta-analyses have reported modest but consistent associations, variations in study design and antibiotic exposure limit the certainty of these findings. Given the widespread use of antibiotics and the growing global cancer burden, a systematic synthesis of the evidence is needed to better understand this relationship and inform preventive strategies. Relevant studies on the relationship between antibiotic use and gastrointestinal (GI) cancer were retrieved from PubMed, Web of Science, Scopus, and Embase. After removing duplicate records, the remaining studies were assessed based on predefined inclusion and exclusion criteria. Data analysis was performed using Comprehensive Meta-Analysis software (version 2). Publication bias was evaluated using Egger's test, and heterogeneity across studies was assessed using the I² statistic. The analyses were conducted using odds ratios (OR) with 95% confidence limits. A total of 12 studies met the inclusion criteria and were incorporated into the meta-analysis. Pooled estimates from a random-effects model (I² = 97.2%) indicated that antibiotic use was associated with an 18.7% higher risk of GI cancers compared with non-use (OR = 1.187, 95% CI: 1.018-1.386, p = 0.029), with no significant evidence of publication bias. Subgroup analysis revealed a significant association with CRC risk (OR = 1.208, 95% CI: 1.027-1.420, p = 0.022), but not with gastroesophageal cancers, likely reflecting limited data in the latter group. Stratification by exposure intensity demonstrated a dose-response relationship: 1-5 antibiotic prescriptions (OR = 1.077, 95% CI: 1.043-1.112) and > 5 prescriptions (OR = 1.154, 95% CI: 1.124-1.186) were both significantly associated with elevated risk. Similarly, short-term (1-15 days), intermediate-term (15-60 days), and long-term (> 60 days) antibiotic use were linked to progressively higher risks, ranging from 11% to 13% increases. Meta-regression confirmed that a greater number of prescriptions was significantly associated with higher GI cancer risk, although the effect size per prescription was small. No significant linear relationship was detected between duration of exposure (days) and risk, and substantial heterogeneity persisted across studies. This systematic review and meta-analysis provide evidence of a modest but statistically significant association between antibiotic use and an increased risk of GI cancers, including CRC. The observed dose-response patterns suggest that repeated or prolonged exposure may confer greater risk. Potential biological mechanisms include antibiotic-induced alterations in gut microbiome composition, promotion of chronic inflammation, and impairment of immune surveillance, all of which may contribute to carcinogenesis. While the relative increases in risk are moderate, the widespread and often indiscriminate use of antibiotics globally amplifies their potential public health impact. These findings underscore the importance of judicious antibiotic prescribing practices and highlight the need for well-designed longitudinal studies with robust control for confounding factors to clarify causality further, identify high-risk subgroups, and inform targeted prevention strategies.