Abstract 2175: Multiple exposures to antibiotics and increased risk of colorectal cancer

Abstract Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States and worldwide. In 2023, approximately 153, 020 individuals will be diagnosed with CRC and 52, 550 will die, including 19, 550 cases and 3750 deaths in patients under 50 years of age. CRC in younger patients (less than 55 years) is known as early onset colorectal cancer (EOCRC). It is a growing global phenomenon whose incidence and mortality has incidence from 11% to 20% between 1995 to 2019 and is expected to increase by 140% by 2030. While it has been linked to known and established risks for CRC, the underlying causes and mechanisms are poorly understood. Based on our current knowledge of the disease, we propose that EOCRC results from exposure of children and young adults to exposome factors that have been increasing globally in the last four decades that may impact the microbiome causing dysbiosis and inflammation in the distal colon and rectum, the anatomical site of EOCRC. Among the likely factors is the use of antibiotics, particularly in infants and children. In this study we hypothesized that early life exposure to antibiotics causes dysbiosis and inflammation in the distal colon and rectum leading to increased mutations and epigenetic events that promote EOCRC development. Specifically, we examined the effect of the most commonly prescribed pediatric antibiotics on the gut microbiota and inflammatory environment in the colon, and their impact on tumor development upon exposure to a carcinogen. We treated A/J mice with multiples rounds of antibiotics and then exposed them to azoxymethane, a carcinogen to determine the effect on tumor development in the colon. The results showed that antibiotic exposure caused dysbiosis and inflammation in the colon of antibiotic treated mice as well as systemic inflammation in mice treated with antibiotics. Treatment with azoxymethane, a carcinogen in the presence of antibiotic-induced dysbiosis led to increased tumor burden in the distal colon. These results suggest a possible involvement of antibiotics on increased risk of EOCRC. Citation Format: Niti Jani, Maredith Richardson, Kristen Hogan, Maria M. Pena. Multiple exposures to antibiotics and increased risk of colorectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2175.