Antibiotic use over several decades is believed to be associated with colorectal adenomas. There is little evidence, however, for the effect of more recent antibiotic use on frequency of colorectal cancers.
A case control study used the RCGP’s Research and Surveillance Centre cohort of patients drawn from NHS England. In all, 35,214 patients with a new diagnosis of colorectal cancer between 1 January 2008 and 31 December 2018 were identified in the database and were matched with 60,348 controls. Conditional logistic regression was used to examine the association between antibiotic prescriptions and colorectal cancer.
A dose-response association between colorectal cancers and prior antibiotic prescriptions was observed. The risk was related to the number and recency of prescriptions with a high number of antibiotic prescriptions over a long period carrying the highest risk. For example, patients prescribed antibiotics in up to 15 years preceding diagnosis were associated with a higher risk of colorectal cancer (odds ratio (OR) = 1.90, 95% confidence intervals (CI), 1.61–2.19, p < 0.001).
Antibiotic use over previous years is associated with subsequent colorectal cancer. While the study design cannot determine causality, the findings suggest another reason for caution in prescribing antibiotics, especially in high volumes and over many years.
Subscribe to Journal
Get full journal access for 1 year
only $20.79 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Louis, P., Hold, G. L. & Flint, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev. Microbiol. 12, 661–672 (2014).
Dulal, S. & Keku, T. O. Gut microbiome and colorectal adenomas. Cancer J. 20, 225–231 (2014).
Akın, H. & Tozun, N. Diet, microbiota, and colorectal cancer. J. Clin. Gastroenterol. 48, s67–s69 (2014).
Yamamoto, M. & Matsumoto, S. Gut microbiota and colorectal cancer. Genes Environ. 38, 1–7 (2016).
Gao, R., Gao, Z., Huang, L. & Qin, H. Gut microbiota and colorectal cancer. Eur. J. Clin. Microbiol. Infect Dis. 36, 757–769 (2017).
Tilg, H., Adolph, T. E., Gerner, R. R. & Moschen, A. R. The intestinal microbiota in colorectal cancer. Cancer Cell 33, 954–964 (2018).
Jahani-Sherafat, S., Alebouyeh, M., Moghim, S., Amoli, H. A. & Ghasemian-Safaei, H. Role of gut microbiota in the pathogenesis of colorectal cancer; a review article. Gastroenterol. Hepatol. Bed Bench 11, 101–109 (2018).
Scanlan, P. D., Shanahan, F., Clune, Y., Collins, J. K., O’Sullivan, G. C., O’Riordan, M. et al. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ. Microbiol. 10, 789–798 (2008).
Wang, T., Cai, G., Qiu, Y., Fei, N., Zhang, M., Pang, X. et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 6, 320–329 (2012).
Tjalsma, H., Boleij, A., Marchesi, J. R. & Dutilh, B. E. A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects. Nature Rev. Microbiol. 10, 575–582 (2012).
Warren, R. L., Freeman, D. J., Pleasance, S., Watson, P., Moore, R. A., Cochraneet, K. et al. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome 1, 1–12 (2013).
Flemer, B., Lynch, D. B., Brown, J. M. R., Jeffery, I. B., Ryan, F. J., Claesson, M. J. et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 66, 633–643 (2017).
Raskov, H., Burcharth, J. & Pommergaard, H. C. Linking gut microbiota to colorectal cancer. J. Cancer 8, 3378–3395 (2017).
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).
Correa, A., Hinton, W., McGovern, A., van Vlymen, J., Yonova, I., Jones, S. et al. Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) sentinel network: a cohort profile. BMJ Open 6, e011092 (2016).
Pathirannehelage, S., Kumarapeli, P., Byford, R., Yonova, I., Ferreira, F. & de Lusignan, S. Uptake of a dashboard designed to give realtime feedback to a sentinel network about key data required for influenza vaccine effectiveness studies. Stud. Health Technol Inform. 247, 161–165 (2018).
Dregan, A., Moller, H., Murray-Thomas, T. & Gulliford, M. C. Validity of cancer diagnosis in a primary care database compared with linked cancer registrations in England. Population-based cohort study. Cancer Epidemiol. 36, 425–429 (2012).
Dolk, F. C. K., Pouwels, K. B., Smith, D. R. M. & Robotham, J. V. Antibiotics in primary care in England: which antibiotics are prescribed and for which conditions? J. Antimicrob. Chemother. 73(Suppl. 2), ii2–ii10 (2018).
Rothman, K. J. No adjustments are needed for multiple comparisons. Epidemiology 1, 43–46 (1990).
Greenland, S. Multiple comparisons and association selection in general epidemiology. Int. J. Epidemiol. 37, 430–434 (2008).
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).
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).
Dik, V. K., van Oijen, M. G. H., Smeets, H. M. & Siersema, P. D. Frequent use of antibiotics is associated with colorectal cancer risk: results of a nested case–control study. Dig. Dis. Sci. 61, 255–264 (2016).
de la Cochetiere, M. F., Durand, T., Lepage, P., Bourreille, A., Galmiche, J. P. & Dore, J. Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J. Clin. Microbiol. 43, 5588–5592 (2005).
Lofmark, S., Jernberg, C., Jansson, J. K. & Edlund, C. Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. & resistance genes. J. Antimicrob. Chemother. 58, 1160–1167 (2006).
Rasmussen, S., Larsen, P. V., Søndergaard, S. E., Elnegaard, S., Svendsen, R. P. & Jarbøl, D. E. Specific and non-specific symptoms of colorectal cancer and contact to general practice. Fam. Pract. 32, 387–394 (2015).
Smith, D., Ballal, M., Hodder, R., Soin, G., Selvachandran, S. N. & Cade, D. Symptomatic presentation of early colorectal cancer. Ann. R Coll. Surg. Engl. 88, 85–190 (2006).
Renzi, C., Lyratzopoulos, G., Card, T., Chu, T. P. C., Macleod, U. & Rachet, B. Do colorectal cancer patients diagnosed as an emergency differ from non-emergency patients in their consultation patterns and symptoms? A longitudinal data-linkage study in England. Br. J. Cancer 115, 866–875 (2016).
Herszényi, L., Barabás, L., Miheller, P. & Tulassay, Z. Colorectal cancer in patients with inflammatory bowel disease: the true impact of the risk. Dig. Dis. 33, 52–57 (2015).
Public Health England. English Surveillance Programme for Antimicrobial Utilisation and Resistance. (Public Health England, 2018)
D.A. and A.D. had the initial idea for the study, CMcG extracted data, A.D. did the analysis and all authors helped in interpreting the findings and drafting the final paper.
Ethics approval and consent to participate
Not applicable. The study involved the analysis of a secondary database containing clinical details of pseudonymised patients
Permission to access the data used in this study can be obtained from the RCGP’s Research and Surveillance Centre (https://www.rcgp.org.uk/clinical-and-research/our-programmes/research-and-surveillance-centre.aspx).
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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).
About this article
Cite this article
Armstrong, D., Dregan, A., Ashworth, M. et al. The association between colorectal cancer and prior antibiotic prescriptions: case control study. Br J Cancer 122, 912–917 (2020). https://doi.org/10.1038/s41416-019-0701-5
British Journal of Cancer (2020)
Clinical Gastroenterology and Hepatology (2020)
A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives