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Serum pepsinogens and risk of gastric and esophageal cancers in the General Population Nutrition Intervention Trial cohort
  1. Jian-Song Ren (jiansongren{at}yahoo.com)
  1. Cancer Institute of the Chinese Academy of Medical Sciences and Peking Union Medical College, China
    1. Farin Kamangar (kamangaf{at}mail.nih.gov)
    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States
      1. You-Lin Qiao
      1. Cancer Institute of the Chinese Academy of Medical Sciences and Peking Union Medical College, China
        1. Philip Taylor (ptaylor{at}mail.nih.gov)
        1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States
          1. Hao Liang
          1. Cancer Institute of the Chinese Academy of Medical Sciences and Peking Union Medical College, China
            1. Sanford Dawsey (dawseys{at}mail.nih.gov)
            1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States
              1. Bin Liu
              1. Cancer Institute of the Chinese Academy of Medical Sciences and Peking Union Medical College, China
                1. Jin-Hu Fan
                1. Cancer Institute of the Chinese Academy of Medical Sciences and Peking Union Medical College, China
                  1. Christian Abnet (abnetc{at}mail.nih.gov)
                  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States

                    Abstract

                    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 noncardia adenocarcinoma, gastric cardia adenocarcinoma, and esophageal squamous cell carcinoma.

                    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 at study baseline.

                    Main outcome measures: Adjusted hazard ratios and 95% confidence intervals for the association between serum PGI/II ratio and caner risk.

                    Results: Compared to subjects with PGI/II ratio of > 4, those with ≤4 had HRs (95%CIs) of 2.72 (1.77-4.20) and 2.12 (1.42-3.16) for noncardia and cardia gastric cancers, respectively. Risk of both cancers were also increased when other cut points ranging from 3 to 6, or when we used quartile models, or nonlinear continuous models. Risk of ESCC was marginally increased in those with PGI/II ratio ≤4, with HR (95% CI) of 1.56 (0.99-2.47), 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 cancer 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 noncardia and cardia gastric adenocarcinomas in subjects with low PGI/II ratio, but little evidence for an association with ESCC risk.

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