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Gut. 2019 Aug 19. pii: gutjnl-2019-318593. doi: 10.1136/gutjnl-2019-318593. [Epub ahead of print]

Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study.

Author information

1
The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
3
Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
4
Department of Medicine, University of East Anglia Norwich Medical School, Norwich, Norfolk, UK.
5
Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich, Norfolk, UK.
6
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
#
Contributed equally

Abstract

BACKGROUND:

Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.

OBJECTIVE:

To assess the association between oral antibiotic use and CRC risk.

DESIGN:

A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.

RESULTS:

28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)).

CONCLUSION:

Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

KEYWORDS:

antibiotics; cancer risk; colorectal cancer; tumor location

PMID:
31427405
DOI:
10.1136/gutjnl-2019-318593

Conflict of interest statement

Competing interests: DP reports grant and patent royalties through institution from Bristol Myers Squibb, grant from Compugen, stock from Trieza Therapeutics and Dracen Pharmaceuticals, and founder equity from Potenza; being consultant for Aduro Biotech, Amgen, Astra Zeneca (Medimmune/Amplimmune), Bayer, DNAtrix, Dynavax Technologies Corporation, Ervaxx, FLX Bio, Rock Springs Capital, Janssen, Merck, Tizona, and Immunomic-Therapeutics; being on the scientific advisory board of Five Prime Therapeutics, Camden Nexus II, WindMil; being on the board of director for Dracen Pharmaceuticals outside the submitted work. SC reports being consultant for Novartis and Theravance outside the submitted work. CS reports a grant from Bristol Myers Squibb for microbiome research outside the submitted work.

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