Antibiotic Use Associated With Risk of Colorectal Polyps in a Nationwide Study

Abstract

Use of antibiotics affects the composition of the microbiome and might affect development of colorectal polyps, which are precursors to colorectal cancer. We performed a nested case-control study in Sweden of 45,744 patients with a colorectal polyp (cases) in the nationwide gastrointestinal ESPRESSO histopathology cohort, using unaffected full siblings as controls (n= 93,307). Polyps were classified by morphology SnoMed codes into conventional adenomas and serrated polyps. Through linkage to the Prescribed Drug Register, we assessed use and cumulative dispensations of antibiotic until 1 year prior to polyp diagnosis for cases and their sibling controls. During a median study period of 6.9 years, compared with non-users, users of antibiotics (including 28,884 cases [63.1%] and 53,222 sibling controls [57.0%]) had a higher risk of colorectal polyps (odds ratio [OR], 1.08; 95% CI, 1.04-1.13). Risk increased with higher number of dispensations (OR for ≥ 6 dispensations, 1.33; 95% CI, 1.25-1.43) (Ptrend < .0001). We observed a stronger association with polyps for broad-spectrum antibiotics (OR comparing users to non-users, 1.23; 95% CI, 1.18-1.29) than for narrow-spectrum antibiotics (OR, 1.05; 95% CI, 1.01-1.10), and for tetracyclines and quinolones (OR, 1.21) than penicillin and other classes (ORs ranged from 1.04 to 1.16). The findings remained robust with several sensitivity analyses, including use of a 2-year lead-in period for antibiotic assessment and correction for misclassification in controls. Use of broad-spectrum antibiotics was more strongly associated with risk of serrated polyps (OR, 1.29; 95% CI, 1.21-1.38) compared with risk of conventional adenomas (OR, 1.17; 95% CI, 1.11-1.24). We found no differences in risk of colon vs rectal polyps with antibiotic use (Pheterogeneity > .10). We found stronger associations for younger (<50 years) vs older adults (≥50 years) for users of quinolones, sulfonamides, trimethoprim, and cephalosporins (Pinteraction < .001). In a nationwide case-control study in Sweden, after accounting for hereditary and early life environmental factors, antibiotic use was associated with increased risk of colorectal polyps. Our findings indicate a role for intestinal dysbiosis in early stages of colorectal carcinogenesis.