Gastric serum biomarkers for long-term risk stratification of gastric and extra-gastric cancers: a 26-year cohort study

Abstract

Gastric serum biomarkers are established for gastric cancer risk assessment, but their utility for extra-gastric malignancies and long-term risk stratification remains unexplored. We prospectively evaluated serum pepsinogens (PGI, PGII), gastrin-17 (G-17) and anti- H. pylori IgG in 20,553 Chinese adults followed for up to 26 years. Associations with cancer incidence, all-cause mortality, and dynamic risk trajectories were assessed using Cox models, restricted cubic splines, and C-statistics. Over a median 13.81-year follow-up, 1832 incident cancers and 2634 deaths occurred. Higher PGII (HR = 1.21) and G-17 (HR = 1.09) were associated with increased overall cancer risk, whereas a higher PGI/II ratio (HR = 0.83) was associated with lower risk. The PGs + clinical-factors model showed a C-statistic of 0.757 for gastric and colorectal cancer risk, with 5.77-fold higher cancer risk and 6.95-fold higher mortality in high-risk individuals, while the G-17 + clinical-factors model showed a C-statistic of 0.610 for overall cancer, with 2.56-fold higher risk and 4.53-fold higher mortality. Risk stratification diverged up to 14 years before gastric or colorectal cancer diagnosis ( P < 0.001) and overall cancer ( P < 0.05). These findings support the potential of serum pepsinogens and gastrin for long-term risk stratification of gastric and colorectal cancers and broader cancer outcomes, enabling earlier identification of individuals at elevated risk.