Metabolic Syndrome Components and Cancer Risk in Normal-Weight Subjects: Systematic Review and Meta-Analysis in over...

Area of Science:

• Metabolic health and cancer epidemiology
• Obesity-related cancer research

Background:

• Metabolic abnormalities may increase cancer risk independently of body weight.
• The role of metabolically unhealthy normal-weight (MUNW) individuals in cancer risk requires further clarification.

Purpose of the Study:

• To determine if MUNW individuals have a higher cancer risk than metabolically healthy normal-weight individuals.
• To analyze cancer risk variations across obesity-related cancer types.
• To identify specific metabolic components predicting cancer risk in normal-weight individuals.

Main Methods:

• Systematic literature search of PubMed, EMBASE, and Web of Science databases up to July 2025.
• Inclusion of longitudinal studies on normal-weight adults classified by metabolic health status.
• Pooled analysis of Hazard Ratios (HR) using a random-effects model.

Main Results:

• Thirty-five studies with over 18 million participants revealed MUNW individuals have a 20% higher cancer risk (HR=1.20).
• Significant risk increases observed for gastric (HR=1.40), pancreatic (HR=1.37), and colorectal cancers (HR=1.34).
• Central adiposity and glucose metabolism abnormalities independently increased cancer risk by 20% (HR=1.20) and 23% (HR=1.23), respectively.

Conclusions:

• Metabolically unhealthy normal-weight individuals face a significantly elevated cancer risk.
• Central adiposity and impaired glucose regulation are key metabolic factors associated with increased cancer risk in normal-weight individuals.
• Routine metabolic screening and phenotyping are vital for identifying at-risk individuals.