Early-onset colorectal cancer as an emerging disease of metabolic dysregulation

Colorectal cancer (CRC) is one of the most common malignancies and the second leading cause of cancer-related death worldwide. Early-onset CRC (EOCRC), diagnosed in adults under the age of 50 years, has emerged as a pressing public health concern owing to its alarming rise in incidence since the 1990s. This trend, observed in the USA and at least eight other high-income countries, starkly contrasts with the declining incidence rates of late-onset CRC (age 50 years and above), largely attributed to early disease detection and lifestyle changes. Concurrent with the rising number of cases of EOCRC, the burden of metabolic diseases, particularly obesity and type 2 diabetes mellitus (T2DM), has surged among young populations. Despite well-documented links between metabolic dysfunction and late-onset CRC, understanding the precise role of obesity and T2DM in the pathogenesis of EOCRC remains in its infancy. This narrative Review synthesizes evidence on the relationship of obesity and T2DM with EOCRC, focusing on pathophysiological mechanisms and the mediating roles of diet and lifestyle factors. It also discusses potential clinical and public health strategies to address obesity and T2DM for EOCRC prevention, highlighting knowledge gaps and future research directions.