Abstract 1055: Antibiotic use and risk of colorectal cancer: A Swedish population-based registry study
Authors: Lu Sai San Moon , Mohammed Zahraa , Häggström Christel , Myte Robin , Lindquist Elisabeth , Gylfe Åsa , Van Guelpen Bethany , Harlid Sophia 
Published: September 2020

Abstract
Background: Antibiotic use has been hypothesized to modify colorectal cancer (CRC) risk by altering the composition of gut microbiota, with some suggestive evidence reported. The aim of the current study was to investigate the possible association between antibiotic use and CRC risk, taking into consideration daily dose, antibiotic type, and tumor location.
Methods: This is a nation-wide, registry-based study with a matched case-control design. All primary CRC cases diagnosed during 2010 to 2016 were selected from the Swedish Colorectal Cancer Register to ensure availability of antibiotic prescription data and a minimum of 5 years of follow-up. Five cancer-free controls were matched to each case for age, sex, and county using the Register of the Total Population. Defined daily doses of antibiotics were extracted from the Swedish Prescribed Drug Register (with complete data from 2005), antibiotic prophylaxis use was estimated using surgical procedural codes from the Swedish National Patient Register, and potential confounders related to socioeconomic status (level of education, country of birth and marital status) were obtained from the LISA database. Multivariable conditional logistic regression was performed to investigate associations between antibiotic use (divided into 5 categories ranging from non-use to very high use (&gt;6months)) and CRC risk.
Results: Our study included 40,545 cases and 202,720 matched controls. We identified a positive, linear association between antibiotic use and CRC risk (adjusted OR for very high users vs non-users = 1.11 (95% CI: 1.03-1.19), p-trend=0.014), which was pronounced for proximal colon cancer (OR = 1.42 (95% CI: 1.28-1.58), p-trend = 1.20 × 10−15), less robust for distal colon and null for rectal cancer. The association was strongest for broad-spectrum beta lactams (adjusted OR =1.50 (95% CI, 1.01-2.23), p-trend=3.12 × 10−6). In contrast, Hiprex, an antibiotic used for treatment and prevention of urinary tract infections, with no known effect on gut microbiota, was not associated with CRC risk (OR = 0.92 (95% CI, 0.81-1.05), p-trend=0.217).
Conclusion: In this registry-based study covering the entire population of Sweden, we identified a robust association between antibiotic use, particularly broad-spectrum beta-lactams, and an increased risk of colon cancer, particularly proximal colon cancer, and a null relationship for rectal cancer. The null findings for Hiprex, which does not affect gut microbiota, lend support to the microbiota hypothesis for the putative influence of antibiotic use in colonic carcinogenesis.
Citation Format: Sai San Moon Lu, Zahraa Mohammed, Christel Häggström, Robin Myte, Elisabeth Lindquist, Åsa Gylfe, Bethany Van Guelpen, Sophia Harlid. Antibiotic use and risk of colorectal cancer: A Swedish population-based registry study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1055.