Regional variations in serum pepsinogen levels and their influencing factors: a multi-center cross-sectional study

Serum pepsinogen (PG) levels are recognized biomarkers influenced by various factors, including lifestyle, Helicobacter pylori (H. pylori) infection status, and the presence of gastric mucosal lesions. However, whether baseline serum PG levels exhibit regional heterogeneity independent of concurrent gastric mucosal lesions has not been clearly established. The study aims to investigate the variability of baseline serum PG levels and identify potential influencing factors across China. Data were collected from individuals undergoing routine health checkups at twelve collaborating medical centers across China between October 2016 and October 2021. Serum pepsinogen I (PGI) and pepsinogen II (PGII) were measured and the pepsinogen I/II ratio (PGR) was calculated; gastroscopy with histopathology was performed to define gastric mucosal status. Detection of H. pylori infection status was performed using histology, serology, and/or breath tests. Lifestyle factors were obtained via standardized questionnaires. Regional differences and associated factors were evaluated using t-tests/ANOVA and multivariable linear regression (Stata 18). A total of 2902 individuals were included in the study. Of them, 2382 was classified as non-atrophic gastritis (NAG), and their regional distribution varied. Baseline serum PG levels significantly varied by regions, except between Southern and Central China. Factors such as H. pylori-positive (including prior eradication), high salt intake, and frequent fruit consumption were significantly associated with baseline serum PGR levels nationwide, with β value (95%CI) being - 2.75 (-3.33, -2.17), 1.66 (0.89, 2.44), and - 2.14 (-2.78, -1.51), respectively. Further analysis stratified by H. pylori infection status showed that both high salt and frequent fruit intake remained significantly associated with PGR. Baseline serum PG levels, independent of gastric mucosal lesions, exhibit significant regional variations across China. These variations are primarily associated with H. pylori infection status and dietary factors. Our findings suggest that region-specific and H. pylori-stratified PG cut-off values may be warranted for gastric cancer (GC) screening, pending prospective validation.