Epidemiology

The association between colorectal cancer and prior antibiotic prescriptions: case control study

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Louis, P., Hold, G. L. & Flint, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev. Microbiol. 12, 661–672 (2014).

    CAS  Article  Google Scholar 

  2. 2.

    Dulal, S. & Keku, T. O. Gut microbiome and colorectal adenomas. Cancer J. 20, 225–231 (2014).

    CAS  Article  Google Scholar 

  3. 3.

    Akın, H. & Tozun, N. Diet, microbiota, and colorectal cancer. J. Clin. Gastroenterol. 48, s67–s69 (2014).

    Article  Google Scholar 

  4. 4.

    Yamamoto, M. & Matsumoto, S. Gut microbiota and colorectal cancer. Genes Environ. 38, 1–7 (2016).

    Article  Google Scholar 

  5. 5.

    Gao, R., Gao, Z., Huang, L. & Qin, H. Gut microbiota and colorectal cancer. Eur. J. Clin. Microbiol. Infect Dis. 36, 757–769 (2017).

    CAS  Article  Google Scholar 

  6. 6.

    Tilg, H., Adolph, T. E., Gerner, R. R. & Moschen, A. R. The intestinal microbiota in colorectal cancer. Cancer Cell 33, 954–964 (2018).

    CAS  Article  Google Scholar 

  7. 7.

    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).

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    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).

    CAS  Article  Google Scholar 

  9. 9.

    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).

    CAS  Article  Google Scholar 

  10. 10.

    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).

    CAS  Article  Google Scholar 

  11. 11.

    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).

    Article  Google Scholar 

  12. 12.

    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).

    CAS  Article  Google Scholar 

  13. 13.

    Raskov, H., Burcharth, J. & Pommergaard, H. C. Linking gut microbiota to colorectal cancer. J. Cancer 8, 3378–3395 (2017).

    Article  Google Scholar 

  14. 14.

    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  Article  Google Scholar 

  15. 15.

    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).

    Article  Google Scholar 

  16. 16.

    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).

    PubMed  Google Scholar 

  17. 17.

    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).

    CAS  Article  Google Scholar 

  18. 18.

    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).

    CAS  Article  Google Scholar 

  19. 19.

    Rothman, K. J. No adjustments are needed for multiple comparisons. Epidemiology 1, 43–46 (1990).

    CAS  Article  Google Scholar 

  20. 20.

    Greenland, S. Multiple comparisons and association selection in general epidemiology. Int. J. Epidemiol. 37, 430–434 (2008).

    Article  Google Scholar 

  21. 21.

    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  Article  Google Scholar 

  22. 22.

    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  Article  Google Scholar 

  23. 23.

    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).

    CAS  Article  Google Scholar 

  24. 24.

    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).

    Article  Google Scholar 

  25. 25.

    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).

    Article  Google Scholar 

  26. 26.

    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).

    PubMed  Google Scholar 

  27. 27.

    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).

    Article  Google Scholar 

  28. 28.

    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).

    CAS  Article  Google Scholar 

  29. 29.

    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).

    Article  Google Scholar 

  30. 30.

    Public Health England. English Surveillance Programme for Antimicrobial Utilisation and Resistance. (Public Health England, 2018)

Download references

Author contributions

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to David Armstrong.

Ethics declarations

Ethics approval and consent to participate

Not applicable. The study involved the analysis of a secondary database containing clinical details of pseudonymised patients

Data availability

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).

Competing interests

The authors declare no competing interests.

Funding information

None.

Additional information

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).

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Download citation

Further reading

Search