Socioeconomic Status Modifies the Risk of Gastric Cancer Through Metabolomic Signature: Evidence From a Prospective Cohort Study

ABSTRACT The role of metabolites in the association between socioeconomic status (SES) and gastric cancer remains unclear. This study seeks to elucidate the role of metabolomics in the association between SES and gastric cancer, as well as to explore potential interactions between metabolic signatures and polygenic risk score (PRS) in the context of gastric cancer. A total of 210,437 participants from the UK Biobank were included in this study. Latent class analysis (LCA) was employed to analyze three indicators—education qualifications, total household income before tax, and employment status—to assess SES. An elastic net regression, coupled with 10‐fold cross‐validation, was employed to develop SES‐related metabolic signatures. The risk of gastric cancer was assessed using a Cox proportional hazards regression model, with adjustments made for confounding variables. During a median follow‐up of 12.6 years, we found that SES‐related metabolic signatures were negatively associated with the risk of gastric cancer, with an adjusted hazard ratio of 0.52 (95% confidence interval [CI]: 0.41–0.65) per standard deviation decrease and an adjusted hazard ratio of 0.68 (95% CI: 0.56–0.83) for high levels compared to low levels. The mediation analysis showed that SES‐related metabolic signatures mediated 9.66% of the association between SES and gastric cancer. The current study identified a range of metabolites affected by SES and revealed that these metabolic signatures partially explained the link between SES and gastric cancer risk, offering insights for potential strategies in preventing gastric cancer.