Metabolic syndrome and colorectal cancer: Mechanisms, epidemiological evidence, and clinical implications

Metabolic syndrome (MetS), characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, has been increasingly recognized as a significant contributor to the development and progression of colorectal cancer (CRC). This review comprehensively summarizes current evidence linking MetS to CRC risk and outcomes from mechanistic, epidemiological, and clinical perspectives. Mechanistic studies suggest that hyperinsulinemia, activation of the insulin-like growth factor axis, chronic systemic inflammation, and adipokine dysregulation create a tumor-promoting environment. Epidemiological data from large-scale cohort studies and meta-analyses consistently demonstrate a positive association between MetS and CRC incidence, with abdominal obesity and hyperglycemia identified as key components. Mendelian randomization studies further support a causal relationship between visceral adiposity and CRC risk. Clinically, MetS is associated with increased risk of recurrence and reduced overall and disease-free survival in CRC patients. Emerging evidence also indicates that persistent metabolic abnormalities may contribute to early-onset CRC. Interventions targeting metabolic health - including lifestyle modification and bariatric surgery - have shown potential in reducing CRC risk and improving outcomes. Despite these advances, heterogeneity in MetS definitions and a paucity of prospective interventional studies limit the generalizability of current findings. Further research is warranted to establish standardized diagnostic criteria, elucidate sex- and age-specific mechanisms, and integrate metabolic profiling into risk stratification frameworks for CRC prevention and management.