Ludmil B. Alexandrov, Paul Brennan, Michael R. Stratton
Colorectal cancer incidence is rising globally among individuals younger than 50 years and remains poorly explained by established risk factors. In this study, we advance the hypothesis that early-childhood exposure to mutagen-producing bacteria contributes to lifetime colorectal cancer risk by imprinting oncogenic mutations in the developing colorectal epithelium, thereby initiating tumorigenesis decades before clinical diagnosis and redefining early-onset colorectal cancer as a disease rooted in early-life mutagenic exposure.