Antibiotic use may increase colorectal cancer risk by altering the gut microbiota. Indeed, emerging data support a pathogenic role of certain bacteria, such as Fusobacterium nucleatum, in colon carcinogenesis (1,2). Although it is well known that factors such as excess body fat and dietary factors, could alter the gut microbiome, the use of antibiotics can have a more disruptive effect (3).

In this study, the authors used data from the comprehensive Swedish national population registers to investigate antibiotics use in relation to colorectal cancer risk (3). This is a nationwide, population-based study with a matched case-control design using a first primary colorectal cancer cases and 5 matched, cancer-free controls. The study included 40 545 colorectal cancer cases and 202 720 controls (3).

The investigators found a positive association between more frequent antibiotics use and colorectal cancer. Importantly, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed (3).

Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. Importantly, the authors found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk (3).

In sum, this register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women.

The main strength of this investigation was the use of high quality, nationwide, registry-based data, allowing them to conduct the largest and most comprehensive original research study to date on antibiotics and colorectal cancer risk (3). Also, the large sample size made it possible to conduct well-powered subgroup analyses on antibiotics type and clinical factors such as disease stage and tumor site (3).

References:

1.    Saus E, Iraola-Guzmán S, Willis JR, Brunet-Vega A, Gabaldón T. Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential. Mol Aspects Med. 2019 Oct;69:93-106. 

2.    Dahmus JD, Kotler DL, Kastenberg DM, Kistler CA. The gut microbiome and colorectal cancer: a review of bacterial pathogenesis. J Gastrointest Oncol. 2018 Aug;9(4):769-777. 

3.    Sai San Moon Lu, MBBS, MPH, Zahraa Mohammed, MD, Christel Häggström, PhD, Robin Myte, PhD, Elisabeth Lindquist, MD, Åsa Gylfe, MD, PhD, Bethany Van Guelpen, MD, PhD, Sophia Harlid, PhD, Antibiotics Use and Subsequent Risk of Colorectal Cancer: A Swedish Nationwide Population-Based Study, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 1, January 2022, Pages 38–46.

Source of images:

1.     Fusobacterium image obtained from the CDC Public Health Image Library. Image credit: CDC/Dr. V. R. Dowell.

2.     Colorectal cancer image: EndoCollab, www.endocollab.com

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