Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


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



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.


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.


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.


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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).


  1. 1.

    Dekker, E., Tanis, P. J., Vleugels, J. L. A., Kasi, P. M. & Wallace, M. B. Colorectal cancer. Lancet 394, 1467–1480 (2019).

    PubMed  Google Scholar 

  2. 2.

    Bray, F., Ferlay, J., Soerjomatram, I., Siegel, R. L., Torre, L. A. & Jemal, A. Global cancer statistics 2018: GLOBOCWN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J. Clin. 68, 394–424 (2018).

    Google Scholar 

  3. 3.

    Araghi, M., Soerjomataram, I., Bardot, A., Ferlay, J., Cabasag, C. J., Morrison, D. S. et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol. Hepatol. 4, 511–518 (2019).

    PubMed  Google Scholar 

  4. 4.

    Mauri, G., Sartore-Bianchi, A., Russo, A. G., Marsoni, S., Bardelli, A. & Siena, S. Early-onset colorectal cancer in young individuals. Mol. Oncol. 13, 109–131 (2019).

    PubMed  Google Scholar 

  5. 5.

    Siegel, R. L., Miller, K. D. & Jemal, A. Cancer Statistics 2018. CA Cancer J. Clin. 68, 7–30 (2018).

    Google Scholar 

  6. 6.

    Arthur, J., Perez-Chanona, E., Muhlbauer, M., Tomkovich, S., Uronis, J., Fan, T. et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338, 120–123 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Castellarin, M., Warren, R., Freeman, J., Dreolini, L., Krzywinski, M., Strauss, J. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22, 299–306 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Kostic, A. D., Gevers, D., Pedamallu, C. S., Michaud, M., Duke, F., Earl, A. M. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292–298 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Zhang, J., Haines, C., Watson, A. J. M., Hart, A. R., Platt, M. J., Pardoll, D. M. et al. Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case-control study. Gut 0, 1–8 (2019).

    Google Scholar 

  10. 10.

    Erdman, S. E. & Poutahidis, T. Gut bacteria and cancer. Biochim. Biophys. Acta. 1856, 86–90 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Ferrer, M., Mendez-Garcia, C., Rojo, D., Barbas, C. & Moya, A. Antibiotic use and microbiome function. Biochem. Pharmacol. 134, 114–126 (2017).

    CAS  PubMed  Google Scholar 

  12. 12.

    Sobhani, I., Tap, J., Roudot-Thoraval, F., Roperch, J. P., Letulle, S., Langella, P. et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS ONE 6, e16393 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Wong, S. H. & Yu, J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat. Rev. Gastroenterol. Hepatol. 16, 690–704 (2019).

    CAS  PubMed  Google Scholar 

  14. 14.

    Tozun, N. & Vardareli, E. Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses. J Clin Gastroenterol 50 Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13–15, 2015, S191-s196 (2016).

  15. 15.

    Francescone, R., Hou, V. & Grivennikov, S. I. Microbiome, Inflammation, and Cancer. Cancer J. 20, 181–189 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Petrelli, F., Ghidini, M., Ghidini, A., Perego, G., Cabiddu, M., Khakoo, S. et al. Use of antibiotics and risk of cancer: a systematic review and meta-analysis of observational studies. Cancers 11, 1174 (2019).

  17. 17.

    Greer, J. B. & O’Keefe, S. J. Microbial induction of immunity, inflammation, and cancer. Front. Physiol. 1, 168 (2011).

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Oh, J. K. & Weiderpass, E. Infection and cancer: global distribution and burden of diseases. Ann. Glob. Health 80, 384–392 (2014).

    PubMed  Google Scholar 

  19. 19.

    Balkwill, F. & Mantovani, A. Inflammation and cancer: back to Virchow? Lancet 357, 539–545 (2001).

    CAS  PubMed  Google Scholar 

  20. 20.

    Yiannakopoulou, E. Aspirin and NSAIDs for breast cancer chemoprevention. Eur. J. Cancer Prev. 24, 416–421 (2015).

    CAS  PubMed  Google Scholar 

  21. 21.

    Bao, C. X., Wang, K., Ding, Y. D. & Kong, J. L. Association between anti-bacterial drug use and digestive system neoplasms: a systematic review and meta-analysis. Front. Oncol. 9, 1298 (2019).

  22. 22.

    Sanyaolu, L. N., Oakley, N. J., Nurmatov, U., Dolwani, S. & Ahmed, H. Antibiotic exposure and the risk of colorectal adenoma and carcinoma: a systematic review and meta-analysis of observational studies. Colorectal Dis. (2019).

  23. 23.

    Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. & Group, P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J. Clin. Epidemiol. 62, 1006–1012 (2009).

    PubMed  Google Scholar 

  24. 24.

    Wells, G., Shea, B. & O’connell, D. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Accessed 20190927 (2000).

  25. 25.

    Sanderson, S., Tatt, I. D. & Higgins, J. P. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int. J. Epidemiol. 36, 666–676 (2007).

    PubMed  Google Scholar 

  26. 26.

    Armitage, P., Berry, G. & Matthews, J. N. S. Statistical Methods in Medical Research. 4th edn (Blackwell Publishing Company: Massachusetts, US, 2002).

  27. 27.

    Orsini, N., Li, R., Wolk, A., Khudyakov, P. & Spiegelman, D. Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am. J. Epidemiol. 175, 66–73 (2012).

    PubMed  Google Scholar 

  28. 28.

    Higgins, J., Thompson, S. & Deeks, J. Measuring inconsistency in meta-analyses. BMJ 327, 557–560 (2003).

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Egger, M., Smith, G., Schneider, M. & Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629–634 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Palmer, T. M., Peters, J. L., Sutton, A. J. & Moreno, S. G. Contour-enhanced funnel plots for meta-analysis. Stata J. 8, 242–254 (2008).

    Google Scholar 

  31. 31.

    Wang, J. L., Chang, C. H., Lin, J. W., Wu, L. C., Chuang, L. M. & Lai, M. S. Infection, antibiotic therapy and risk of colorectal cancer: a nationwide nested case-control study in patients with Type 2 diabetes mellitus. Int. J. Cancer 135, 956–967 (2014).

    CAS  PubMed  Google Scholar 

  32. 32.

    Friedman, G. D., Jiang, S. F., Udaltsova, N., Quesenberry, C. P. Jr., Chan, J. & Habel, L. A. Epidemiologic evaluation of pharmaceuticals with limited evidence of carcinogenicity. Int. J. Cancer 125, 2173–2178 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Friedman, G. D., Coates, A. O., Potter, J. D. & Slattery, M. L. Drugs and colon cancer. Pharmacoepidemio. Drug Saf. 7, 99–106 (1998).

    CAS  Google Scholar 

  34. 34.

    Dik, V. K., van Oijen, M. G., Smeets, H. M. & Siersema, P. D. Frequent use of antibiotics is associated with colorectal cancer risk: results of a nested case-control study. Digestive Dis. Sci. 61, 255–264 (2016).

    CAS  Google Scholar 

  35. 35.

    Boursi, B., Haynes, K., Mamtani, R. & Yang, Y. X. Impact of antibiotic exposure on the risk of colorectal cancer. Pharmacoepidemiol. Drug Saf. 24, 534–542 (2015).

    CAS  PubMed  Google Scholar 

  36. 36.

    Kilkkinen, A., Rissanen, H., Klaukka, T., Pukkala, E., Heliovaara, M., Huovinen, P. et al. Antibiotic use predicts an increased risk of cancer. Int. J. Cancer 123, 2152–2155 (2008).

    CAS  PubMed  Google Scholar 

  37. 37.

    Falagas, M. E., Walker, A. M., Jick, H., Ruthazer, R., Griffith, J. & Snydman, D. R. Late incidence of cancer after metronidazole use: a matched metronidazole user/nonuser study. Clin. Infect. Dis. 26, 384–388 (1998).

    CAS  PubMed  Google Scholar 

  38. 38.

    Didham, R. C., Reith, D. M., McConnell, D. W. & Harrison, K. S. Antibiotic exposure and breast cancer in New Zealand. Breast Cancer Res. Treat. 92, 163–167 (2005).

    CAS  PubMed  Google Scholar 

  39. 39.

    Armstrong, D., Dregan, A., Ashworth, M., White, P., McGee, C. & de Lusignan, S. The association between colorectal cancer and prior antibiotic prescriptions: case control study. Br. J. Cancer. (2020).

  40. 40.

    Brusselaers, N. Prescribed Drugs and the Microbiome. Gastroenterol. Clin. North Am. 48, 331–342 (2019).

    PubMed  Google Scholar 

  41. 41.

    Grigoryan, L., Germanos, G., Zoorob, R., Juneja, S., Raphael, J. L., Paasche-Orlow, M. K. et al. Use of antibiotics without a prescription in the U.S. population: a scoping review. Ann. Intern. Med. (2019).

  42. 42.

    Zhang, H., Garcia Rodriguez, L. A. & Hernandez-Diaz, S. Antibiotic use and the risk of lung cancer. Cancer Epidemiol. Biomark. Prev. 17, 1308–1315 (2008).

    CAS  Google Scholar 

  43. 43.

    Velicer, C. M., Lampe, J. W., Heckbert, S. R., Potter, J. D. & Taplin, S. H. Hypothesis: is antibiotic use associated with breast cancer? Cancer Causes Control. 14, 739–747 (2003).

    PubMed  Google Scholar 

  44. 44.

    Ma, W. & Chan, A. T. Antibiotic use and colorectal cancer: a causal association? Gut. (2019).

  45. 45.

    Cao, Y., Wu, K., Mehta, R., Drew, D. A., Song, M., Lochhead, P. et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut 67, 672–678 (2018).

    CAS  PubMed  Google Scholar 

  46. 46.

    Kim, S. Y., Park, H. J., Kim, H. S., Park, D. I., Cha, J. M., Park, S. J. et al. Cap-assisted chromoendoscopy using a mounted cap versus standard colonoscopy for adenoma detection. Am. J. Gastroenterol. 115, 465–472 (2020).

    PubMed  Google Scholar 

  47. 47.

    Adami, H. O., Kalager, M., Valdimarsdottir, U., Bretthauer, M. & Ioannidis, J. P. A. Author Reply to: the name of the game: is preventive screening “cancer screening?”. Eur. J. Clin. Invest. (2019).

  48. 48.

    Hibberd, A. A., Lyra, A., Ouwehand, A. C., Rolny, P., Lindegren, H., Cedgard, L. et al. Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol. 4, e000145 (2017).

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Saus, E., Iraola-Guzman, S., Willis, J. R., Brunet-Vega, A. & Gabaldon, T. Microbiome and colorectal cancer: roles in carcinogenesis and clinical potential. Mol. Asp. Med. 69, 93–106 (2019).

    CAS  Google Scholar 

  50. 50.

    Kester, J. C., Brubaker, D. K., Velazquez, J., Wright, C., Lauffenburger, D. A. & Griffith, L. G. Clostridioides difficile-associated antibiotics alter human mucosal barrier functions by microbiome-independent mechanisms. Antimicrob. Agents Chemother. (2020).

  51. 51.

    Thomas, A. M., Manghi, P., Asnicar, F., Pasolli, E., Armanini, F., Zolfo, M. et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat. Med. 25, 667–678 (2019).

    CAS  PubMed  Google Scholar 

  52. 52.

    Gagniere, J., Raisch, J., Veziant, J., Barnich, N., Bonnet, R., Buc, E. et al. Gut microbiota imbalance and colorectal cancer. World J. Gastroenterol. 22, 501–518 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Velicer, C. M., Heckbert, S. R., Lampe, J. W., Potter, J. D., Robertson, C. A. & Taplin, S. H. Antibiotic use in relation to the risk of breast cancer. JAMA 291, 827–835 (2004).

    CAS  PubMed  Google Scholar 

  54. 54.

    Tamim, H. M., Musallam, K. M., Al Kadri, H. M., Boivin, J. F. & Collet, J. P. Antibiotic use and risk of gynecological cancer. Eur. J. Obstet. Gynecol. Reprod. Biol. 159, 388–393 (2011).

    CAS  PubMed  Google Scholar 

Download references


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

Author information




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.

Corresponding author

Correspondence to Johanna Simin.

Ethics declarations

Ethics approval and consent to participate

No ethical approval or consent to participate was required for this systematic review and dose–response meta-analysis, since data were collected and synthesised from previous studies.

Consent to publish

Not applicable.

Data availability

All relevant data is available in this study.

Competing interests

The authors declare no conflicts of interests.

Funding information

No funding was acquired for this study.

Additional information

Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

Further reading


Quick links