Early-onset colorectal cancer (EOCRC) refers to colorectal cancer (CRC) diagnosed in adults younger than 50 years. We conducted this systematic review and meta-analysis to estimate EOCRC incidence, ev...

Early-life exposure to lifestyle-associated metabolic alterations could be a key contributor to early-onset colorectal cancer (EOCRC). Notably, insulin resistance (InsR)-linked hyperinsulinemia, elevated levels of insulin-like growth factors, and chronic inflammation could trigger EOCRC by modulating gene expression/pathways that support carcinogenesis/anti-apoptosis. Here, we discuss how InsR could be the trigger that offsets metabolic homeostasis in young individuals, leading to EOCRC. Furthermore, we emphasize the need for lifestyle interventions, early detection, and targeted therapeutic interventions to mitigate this growing health concern.

The incidence of colorectal cancer (CRC) is rising rapidly in people younger than 50 years. Although this increase parallels shifts in lifestyle and environmental factors—collectively termed the exposome—whether these are indeed linked to the development of early-onset CRC (EOCRC) remains uninvestigated. Due to limited exposome data in most cancer cohorts, we constructed weighted methylation risk scores as proxies for exposome exposure to pinpoint specific risk factors associated with EOCRC compared to late-onset CRC (LOCRC) patients diagnosed at ≥70 years. Our analysis confirmed previously identified risk factors, including educational attainment, diet and smoking habits. Moreover, we identified exposure to the herbicide picloram as a new risk factor (adjusted P = 4.4 × 10−4) in the discovery cohort (31 EOCRC versus 100 LOCRC), which was replicated in a meta-analysis comprising nine CRC cohorts (P = 3.1 × 10−3; adjusted P = 1.5 × 10−2; 83 EOCRC versus 272 LOCRC). Subsequently, we anal

Early-life exposure to lifestyle-associated metabolic alterations could be a key contributor to early-onset colorectal cancer (EOCRC). Notably, insulin resistance (InsR)-linked hyperinsulinemia, elevated levels of insulin-like growth factors, and chronic inflammation could trigger EOCRC by modulating gene expression/pathways that support carcinogenesis/anti-apoptosis. Here, we discuss how InsR could be the trigger that offsets metabolic homeostasis in young individuals, leading to EOCRC. Furthermore, we emphasize the need for lifestyle interventions, early detection, and targeted therapeutic interventions to mitigate this growing health concern.

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