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Epidemiology

Antibiotic use and risk of colorectal cancer: a systematic review and dose–response meta-analysis

Abstract

Background

It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present.

Design

Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose–response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models.

Results

Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05–1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26–2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93–1.32). The dose–response analysis did not provide strong evidence of any particular dose–response association, and the risk patterns were rather similar for colon and rectal cancer.

Discussion

The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug–microbiome interactions.

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Fig. 1: Study selection.
Fig. 2: Forest plot of the most adjusted relative risks for the association of oral antibiotic use with colorectal cancer risk, ever-users compared to non-users.
Fig. 3: Forest plot for the association of antibiotic use with colorectal cancer, stratified by the different antibiotic classes.
Fig. 4: Dose–response relationship of any antibiotic use with colon and rectal cancer, including detection of non-linearity (p for non-linearity <0.0005).

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Acknowledgements

We thank Karolinska Institutet University Library for their valuable help in assisting us in the systematic literature search.

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J.S. had full access to all data in the study. J.S. takes full responsibility for the integrity of the data and the accuracy of the data analysis. Study plan and design: J.S., R.F., Q.L., R.S.O., S.C., L.E. and N.B.. Data collection and preparation for analysis: J.S. and R.F. Data selection: J.S. and N.B.. Statistical analysis: J.S. Analysis and interpretation of the data: J.S., R.F., Q.L., R.S.O., S.C., L.E. and N.B. Drafting of the paper: J.S. Critical revision of the paper for important intellectual content: J.S., R.F., Q.L., R.S.O., S.C., L.E. and N.B.

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Correspondence to Johanna Simin.

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Simin, J., Fornes, R., Liu, Q. et al. Antibiotic use and risk of colorectal cancer: a systematic review and dose–response meta-analysis. Br J Cancer 123, 1825–1832 (2020). https://doi.org/10.1038/s41416-020-01082-2

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