Objective: Low serum pepsinogen I (PGI) and low pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy. We aimed to prospectively test the association between serum PGI/II ratio and risks of gastric non-cardia adenocarcinoma, gastric cardia adenocarcinoma, and oesophageal squamous cell carcinoma (OSCC).
Design: Case–cohort study nested in a prospective cohort with over 15 years of follow-up.
Setting: Rural region of the People’s Republic of China.
Subjects: Men and women aged 40–69 years at study baseline.
Main outcome measures: Adjusted hazard ratios and 95% confidence intervals for the association between serum PGI/II ratio and cancer risk.
Results: Compared to subjects with PGI/II ratio of >4, those with ⩽4 had hazard ratios (HRs) (95% CIs) of 2.72 (1.77 to 4.20) and 2.12 (1.42 to 3.16) for non-cardia and cardia gastric adenocarcinomas, respectively. Risk of both cancers was also increased when we used other cut points ranging from 3 to 6, or quartile models, or nonlinear continuous models. Risk of OSCC was marginally increased in those with PGI/II ratio ⩽4, with HR (95% CI) of 1.56 (0.99 to 2.47), but quartile models and continuous models showed no increased risk. The nonlinear continuous models suggested that any single cut point collapsed subjects with dissimilar gastric adenocarcinoma risks, and that using cut points was not an efficient use of data in evaluating these associations.
Conclusion: In this prospective study, we found similar and significantly increased risks of non-cardia and cardia gastric adenocarcinomas in subjects with low PGI/II ratio but little evidence for an association with the risk of OSCC.
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Funding: This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and by NCI contracts number N01-SC-91030, N01-RC-47701 and N01-RC-47702, and by funds from the Cancer Institute, Chinese Academy of Medical Sciences.
Competing interests: None.
Ethics approval: The conduct of the Linxian General Population Nutrition Intervention Trial and extended follow-up was approved by the institutional review boards of the Cancer Institute of the Chinese Academy of Medical Sciences and the US National Cancer Institute and has been approved annually since 1985.