Shaping the future of early-onset colorectal cancer prevention

Early-onset colorectal cancer (EOCRC) among individuals under age 50 is increasing globally. Lifestyle factors such as obesity, metabolic comorbid conditions, poor diet and sedentary behaviours are linked to EOCRC, but critical gaps remain in identifying additional risk factors, with growing evidence for early-life and gut microbial-related exposures. In addition, how or when the risk factors act, individually or collectively, to initiate or promote colorectal cancer at much younger ages remains unknown. Compounding the complexity are the unique challenges of developing and implementing effective prevention strategies among younger populations. In this Roadmap, we review the progress and challenges of risk factor discovery for EOCRC, highlight opportunities for prevention and propose a transdisciplinary framework integrating population, mechanistic, behavioural and implementation sciences to accelerate causal risk factor discovery and translate insights into strategies to reverse the rising EOCRC burden. This framework, exemplified by emerging global initiatives including the Cancer Grand Challenges team PROSPECT, is broadly adaptable and intended to inspire collaborative efforts across the field. We also emphasize the critical role of patient perspectives and public engagement in shaping these efforts. With the urgency in risk factor discovery, scientists, the public and policymakers must unite to transform knowledge into life-saving solutions for future generations.