Abstract
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.
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Data availability
The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
Abbreviations
- PG:
-
pepsinogen
- PGI:
-
pepsinogen I
- PGII:
-
pepsinogen II
- PGR:
-
pepsinogen I/II ratio
- H.pylori:
-
Helicobacter pylori
- NAG:
-
non-atrophic gastritis
- GC:
-
gastric cancer
- AG:
-
atrophic gastritis
- IM:
-
intestinal metaplasia
- OLGA:
-
the Operative Link on Gastritis assessment
- MAG:
-
mild-to-moderate atrophic gastritis
- SAG:
-
severe atrophic gastritis
- IQR:
-
interquartile range
- SD:
-
standard deviation
- MMSE:
-
Mini-Mental State Examination
- PPI:
-
proton pump inhibitor
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Acknowledgements
This research was supported by No. 924 Hospital of the People’s Liberation Army of China, the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhongshan Hospital affiliated to Xiamen University, Traditional Chinese Medicine Hospital of Kunshan, the Second Military Medical University, Ningbo No.1 Hospital, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Sichuan Provincial People’s Hospital, the First Hospital affiliated to AMU, Jilin People’s Hospital, Chinese PLA Hospital, Jinzhou Hospital of Traditional Chinese Medicine. We express gratitude to all participating hospitals.
Funding
National Major Science and Technology Program of China (Grant No. 2024ZD0522301); National Key Research and Development Program of China (Grant No. 2022YFF0902004).
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HJJ performed data analysis and interpretation, and was a major contributor in writing the manuscript. YJY contributed significantly to the conception and design of the study. TYL critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.
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The study was approved by the Human Research Ethics Committee of the participating hospitals (approval number: 2024 − 1181 at the Second Affiliated Hospital of Zhejiang University, the leading study site). All participants signed an informed consent form in accordance with the Declaration of Helsinki.
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Jiaojiao, H., Jiaying, Y. & Yuling, T. Regional variations in serum pepsinogen levels and their influencing factors: a multi-center cross-sectional study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38326-9
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DOI: https://doi.org/10.1038/s41598-026-38326-9
