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

Abstract

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.

Keywords: Metabolic syndrome; Colorectal cancer; Insulin resistance; Chronic inflammation; Abdominal obesity; Hyperglycemia

Core Tip: This comprehensive review highlights the emerging role of metabolic syndrome (MetS) as a critical modifiable risk factor in colorectal cancer (CRC) initiation, progression, and prognosis. It synthesizes mechanistic evidence involving insulin resistance, chronic inflammation, and adipokine dysregulation, and consolidates global epidemiological data linking MetS - especially abdominal obesity and hyperglycemia - to increased CRC incidence and mortality. The review also discusses the adverse impact of MetS on CRC outcomes, including recurrence and survival, and evaluates the potential of lifestyle and surgical interventions in mitigating these risks. This article underscores the importance of integrating metabolic health assessment into personalized CRC prevention and management strategies.