Impact of antibiotic exposure on the risk of colorectal cancer

Abstract

Purpose: Gut microbiota has been postulated to serve as a significant promoter of CRC formation, and colonic dysbiosis was previously reported in CRC tissue. Our aim was to evaluate the association between the type and cumulative duration of antibiotic exposure and CRC risk.

Methods: We conducted a nested case-control study using a large population-based database from the UK. Cases were defined as those with any medical code of CRC. Subjects with known familial CRC syndromes or IBD were excluded from the study. For every case, four eligible controls matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy before index date. Adjusted ORs and 95%CIs were estimated using conditional logistic regression analysis.

Results: A total of 20,990 cases and 82,054 controls were identified. The adjusted OR for CRC among subjects first exposed to penicillins >10 years prior to index date was 1.11 (95%CI 1.02-1.20). The risk increased significantly with the number of penicillin exposures up to 1.20 (95%CI 1.11-1.31) for >10 courses. The risk also increased with the average number of penicillin treatments per-year (exposure intensity) with an OR of 1.04 (95%CI 1.01-1.08) per one additional treatment per year. Exposure to anti-viral or anti-fungal therapy was not associated with CRC risk.

Conclusions: Past exposure to multiple courses of penicillins is related to a modest elevation in CRC risk.

Keywords: antibiotic; cancer; colorectal; penicillin; pharmacoepidemiology; risk factor.