Early-onset colorectal cancer is associated with metabolic disorders: a systematic review and meta-analysis

Early-onset colorectal cancer (eoCRC), defined by diagnosis before age 50, is increasing worldwide. Metabolic disorders are suspected contributors. We performed a systematic review and meta-analysis to quantify associations between eoCRC and obesity, type 2 diabetes, hyperlipidemia, arterial hypertension and metabolic syndrome. We systematically searched MEDLINE, Cochrane Central Register of systematic reviews, EMBASE, ClinicalTrials.gov, and Web of Science from March 2023 to December 2024. A univariate meta-analysis was performed for outcomes with at least four studies and comparable means of association. 38 studies were included. Obesity at diagnosis was associated significantly with a 1.45-fold increased risk of eoCRC. Elevated BMI during late adolescence, at age 20, and at age 30 were associated with higher eoCRC risk in multiple cohort studies. as independent risk factors. Among male individuals aged 20-49, Type 2 diabetes increased eoCRC risk, with affected individuals exhibiting a 10-year colorectal cancer risk comparable to that of the general population at age 50,but occurring 4-5 years earlier. Additional positive associations were reported for hyperlipidemia (ages 20-39), arterial hypertension in males (ages 20-39), and metabolic syndrome, although findings were heterogeneous. A higher number of metabolic comorbidities was positively correlated with increased eoCRC risk. Early metabolic dysregulation appears to accelerate colorectal carcinogenesis, increasing the impact of metabolic risk factors at younger ages. As metabolic disorders rise among adolescents and young adults, the eoCRC burden likely will grow. Life-course studies integrating metabolic trajectories, molecular biomarkers, epidemiologic data while accounting for screening exposure are needed to clarify causal pathways and guide prevention and screening.