Serum pepsinogens and risk of gastric and oesophageal cancers in the General Population Nutrition Intervention Trial cohort.

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 <or=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 <or=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.