Abstract A012: Early life exposure to antibiotics and increased risk of early onset colorectal cancer


 The incidence of early onset colorectal cancer (EOCRC), colorectal cancer in individuals younger than fifty years old, has steadily increase in the past few decades in the US and around the world and is predicted to increase by 140% by 2030 [1]. Epidemiological studies have linked EOCRC to heredity, obesity and other causative agents; however, these are also linked to late onset CRC. Thus, the causes and underlying mechanisms as to why otherwise healthy individuals are susceptible to EOCRC remain poorly understood. We proposed that increased risk to EOCRC is driven by exposomes whose entry into the global environment precedes and parallels the increased incidence of EOCRC, that impact the gut microbiome and distal colon environment, and to which individuals are exposed at different developmental stages in life [2]. In this study, we examine the role of exposure to antibiotics during development on risk of EOCRC. Antibiotics are indispensable in our fight against infections; however, their overuse has become a public health concern with over a billion doses prescribed globally ever year [3], and their use in infants and children remains very high [4]. Exposure early in life has the potential to alter the gut microbiota permanently and cause dysbiosis leading to inflammation in the gut and altered immune development, both of which are known to increase the risk of CRC. In this study, we test the hypothesis that multiple exposures to commonly prescribed childhood antibiotics will cause dysbiosis and inflammation in the distal colon and increase the risk of EOCRC. We treated A/J mice with the most commonly prescribed classes of antibiotics to treat infections in children and assessed their effects on the colon environment and on tumor development upon exposure to azoxymethane (AOM). The results showed that antibiotics caused dysbiosis that permanently altered the gut microbiome composition, induced inflammation in the colon, and altered tumor burden in the distal colon. The results will allow us to determine the underlying mechanisms by which antibiotics may impact EOCRC, identify individuals who may be at higher risk, and develop viable strategies to minimize risk of EOCRC. References: 1. Bailey, C.E., et al., Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg, 2015. 150(1): p. 17-22. 2. Hofseth, L.J., et al., Early-onset colorectal cancer: initial clues and current views. Nat Rev Gastroenterol Hepatol, 2020. 17(6): p. 352-364. 3. Zhang, J., et al., Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study. Gut, 2019. 68(11): p. 1971-1978. 4. Finkelstein, J.A., et al., Reduction in antibiotic use among US children, 1996-2000. Pediatrics, 2003. 112(3 Pt 1): p. 620-7.
 Citation Format: Niti A. Jani, Kristen M. Hogan, Maredith L. Richardson, Maria M. Pena. Early life exposure to antibiotics and increased risk of early onset colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A012.