Colorectal Cancer in the Era of Early-Onset Disease — A Global Perspective

Abstract Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide, accounting for approximately 1.9 million new cases and more than 900,000 deaths annually [1]. Over the last two decades, population-based screening programs have contributed to a significant decline in both incidence and mortality among individuals older than 50 years [2]. In contrast, a consistent and alarming increase in early-onset colorectal cancer (EOCRC), defined as CRC diagnosed before the age of 50, has been observed across multiple geographic regions [3–5]. This epidemiological divergence reflects a complex interplay of metabolic dysfunction, chronic inflammation, microbiome alterations, environmental exposures, and genetic susceptibility [6–9]. Importantly, EOCRC is increasingly recognized as a biologically and clinically distinct entity rather than simply an earlier manifestation of conventional CRC [10]. This article provides an integrated and expanded overview of EOCRC, linking global epidemiological trends with underlying biological mechanisms and clinical implications. Particular emphasis is placed on how early-life exposures and molecular heterogeneity influence disease development, and how these insights should reshape screening strategies, diagnostic awareness, and precision oncology approaches.