Metabolic Syndrome, Component Burden, and Incident Gastric Cancer Risk: A Prospective Cohort Study in the UK Biobank
Abstract As Helicobacter pylori prevalence declines, understanding the contribution of modifiable systemic factors to gastric cancer risk becomes increasingly important. We evaluated the association of metabolic syndrome (MetS), its individual components, and anatomic subsites with incident gastric cancer in 471,540 UK Biobank participants. Multivariable Cox proportional hazards models were used to estimate the risk of overall, cardia, and non-cardia gastric cancers, and restricted cubic splines were used for exploratory nonlinear analyses. Over a mean follow-up of 6.5 years, 332 incident gastric cancer cases were identified. In the fully adjusted model, baseline MetS was associated with increased gastric cancer risk [HR = 1.36; 95% confidence interval (CI), 1.08–1.71]. A positive trend was observed with the accumulation of metabolic components (P for trend = 0.033). Subsite analyses showed a directionally positive association for cardia gastric cancer (HR = 1.48; 95% CI, 1.03–2.11) and a nonsignificant positive association for non-cardia gastric cancer (HR = 1.28; 95% CI, 0.95–1.73); however, formal testing found no statistical evidence of subsite heterogeneity (P for heterogeneity = 0.547). Exploratory spline analysis suggested a possible nonlinear association for systolic blood pressure. Overall, MetS and the accumulation of its components were associated with a moderately increased risk of gastric cancer. Waist circumference showed the most consistent component-level signal, and further studies are needed to clarify the role of metabolic health in gastric cancer risk assessment. Significance: In this prospective analysis of 471,540 UK Biobank participants, MetS was associated with a moderately increased risk of incident gastric cancer. A positive trend was observed with cumulative metabolic component burden, and waist circumference showed the most consistent component-level signal. Subsite analyses suggested a stronger point estimate for cardia gastric cancer, but formal testing found no statistical evidence of heterogeneity between cardia and non-cardia tumors.