Metabolic Syndrome, Component Burden, and Incident Gastric Cancer Risk: A Prospective Cohort Study in the UK Biobank

As Helicobacter pylori prevalence declines, understanding the contribution of modifiable systemic factors to gastric cancer (GC) risk becomes increasingly important. We evaluated the association of metabolic syndrome (MetS), its individual components, and anatomical subsites with incident GC in 471,540 UK Biobank participants. Multivariable Cox proportional hazards models were used to estimate the risk of overall, cardia, and non-cardia GC, and restricted cubic splines were used for exploratory non-linear analyses. Over a mean follow-up of 6.5 years, 332 incident GC cases were identified. In the fully adjusted model, baseline MetS was associated with increased GC risk (HR = 1.36, 95% CI: 1.08-1.71). A positive trend was observed with the accumulation of metabolic components (P trend = 0.033). Subsite analyses showed a directionally positive association for cardia GC (HR = 1.48, 95% CI: 1.03-2.11) and a non-significant positive association for non-cardia GC (HR = 1.28, 95% CI: 0.95-1.73); however, formal testing found no statistical evidence of subsite heterogeneity (P heterogeneity = 0.547). Exploratory spline analysis suggested a possible non-linear association for systolic blood pressure. Overall, MetS and the accumulation of its components were associated with a moderately increased risk of GC. Waist circumference showed the most consistent component-level signal, and further studies are needed to clarify the role of metabolic health in GC risk assessment.