Serum Gastrin and the Pepsinogen I/II Ratio as Markers for Diagnosis of Premalignant Gastric Lesions

  • Shafaghi, Afshin (Division of Gastroenterology and Hepatology, Guilan University of Medical Sciences) ;
  • Mansour-Ghanaei, Fariborz (Division of Gastroenterology and Hepatology, Guilan University of Medical Sciences) ;
  • Joukar, Farahnaz (Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences) ;
  • Sharafkhah, Maryam (Biostatistics, Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital) ;
  • Mesbah, Alireza (Razi Pathobiology Laboratory, Tehran University of Medical Sciences, Shariati Hospital) ;
  • Askari, Kurosh (Pathology Department, Guilan University of Medical Sciences) ;
  • Geranmayeh, Siamak (Sina Pathobiology Laboratory, Tehran University of Medical Sciences, Shariati Hospital) ;
  • Mehrvarz, Alireza (Afra Pathobiology Laboratory, Rasht, Tehran University of Medical Sciences, Shariati Hospital) ;
  • Souti, Fatemeh (Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences) ;
  • Sokhanvar, Homayoon (Division of Gastroenterology and Hepatology, Guilan University of Medical Sciences) ;
  • Fakhrieh, Saba (Division of Gastroenterology and Hepatology, Guilan University of Medical Sciences) ;
  • Aminian, Keyvan (Division of Gastroenterology and Hepatology, Guilan University of Medical Sciences) ;
  • Yousefi-Mashhour, Mahmud (Division of Gastroenterology and Hepatology, Guilan University of Medical Sciences) ;
  • Khosh-Sorur, Mahmud (Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences) ;
  • Rasoulian, Javid (Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences)
  • Published : 2013.06.30


Background: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. Methods: A cross-sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. Results: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). Conclusions: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.


Gastrin;pepsinogen I;pepsinogen II;preneoplastic lesion;gastric cancer;Northern Iran


  1. Axon A (2002). Gastric cancer and Helicobacter pylori. Aliment Pharmacol Ther, 16, 83-8.
  2. Borch K, Axelsson CK, Halgreen H, et al (1989). The ratio of pepsinogen A to pepsinogen C: a sensitive test for atrophic gastritis. Scand J Gastroenterol, 24, 870-6
  3. Carneiro F, Machado JC, David L, (2001). Current thoughts on the histopathogenesis of gastric cancer. Eur J Cancer Prev, 10, 101-2.
  4. Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, et al (2004). Validity of serum Pepsinogen I/II ratio for the diagnosis of gastric epithelial dysplasia and intestinal metaplasia during the follow-up of patients at risk for intestinal-type gastric adenocarcinoma. Neoplasia, 6, 449-56.
  5. Haj-Sheykholeslami A, Rakhshani N, Amirzargar A, et al (2008). Serum pepsinogen I, pepsinogen II, and gastrin 17 in relatives of gastric cancer patients: comparative study with type and severity of gastritis. Clin Gastroenterol Hepatol, 6, 174-9.
  6. Iijima K, Abe Y, Kikuchi R, et al (2009). Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal, healthy stomach. World J Gastroenterol, 15, 853-9.
  7. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  8. Karnes WE Jr, Samloff IM, Siurala M, et al (1991). Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Gastroenterology , 101, 167-74
  9. Kikuchi R, Abe Y, Iijima K, et al (2011). Low serum levels of pepsinogen and gastrin 17 are predictive of extensive gastric atrophy with high-risk of early gastric cancer. Tohoku J Exp Med, 223, 35-44.
  10. Kitahara F, Kashiwagi A, Kanai T, et al (1996). A role of pepsinogen assay as the first cancer screening before screening by gastroscopy. J Gastroenterological Mass Survey, 116, 42-8.
  11. Kitahara F, Kobayashi K, Sato T, et al (1999). Accuracy of screening for gastric cancer using serum pepsinogen concentrations. Gut, 44, 693-7.
  12. Kodoi A, Yoshihara M, Sumii K, et al (1995). Serum pepsinogen in screening for gastric cancer. J Gastroenterol, 30, 452-60.
  13. Kwon YM, Lim HT, Lee K, et al (2009). Factors associated with use of gastric cancer screening services in Korea. World J Gastroenterol, 15, 3653-9.
  14. Maconi G, Manes G, Porro GB (2008). Role of symptoms in diagnosis and outcome of gastric cancer. World J Gastroenterol, 14, 1149-55.
  15. Malekzadeh R, Derakhshan MH, Malekzadeh Z (2009).Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med, 12, 576-83.
  16. Mansour-Ghanaei F, Joukar F, Soati F, Mansour-Ghanaei A, Bakhshizadeh Naserani S (2012). Knowledge about gastric carcinoma in North of Iran, a high prevalent region for gastric carcinoma: a population-based telephone survey. Asian Pac J Cancer Prev, 13, 3361-6.
  17. Mansour-Ghanaei F, Sokhanvar H, Joukar F, et al (2010). Endoscopic findings in a mass screening program for cancer in a high risk region- Guilan province of Iran. Asian Pac J Cancer Prev, 13, 1407-12.
  18. Miki K (2011). Gastric cancer screening by combined assay for serum anti-Helicobacter Gastric cancer screening by combined assay for serum anti-Helicobacter. Proc Jpn Acad Ser B Phys Biol Sci, 87, 405-14.
  19. Miki K, Ichinose M, Ishikawa KB, et al (1993). Clinical application of serum pepsinogen I and II levels for mass screening to detect gastric cancer. Jpn J Cancer Res, 84, 1086-90.
  20. Miki K (1992). Mass screening of stomach neoplasms by serum pepsinogen analysis. J Jpn Society of Internal Med, 81, 654-9.
  21. Miki K, Ichinose M, Kawamura N, et al (1989). The significance of low serum pepsinogen levels to detect stomach cancer associated with extensive chronic a gastritis in Japanese subjects. Jpn J Cancer Res, 80, 111-14.
  22. Nasrollahzade D, Aghcheli K, Sotoudeh M, et al (2011). Accuracy and cut-off values of pepsinogens I,II, and Gastrin 17 for diagnosis of gastric fundic atrophy: Influence of gastritis. PLoS one, 6, 26957.
  23. Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.
  24. Parkin DM (2004). International variation. Oncogene, 23, 6329-40.
  25. Parkin DM, Bray FI, Devesa SS (2001). Cancer burden in the year 2000. The global picture. Eur J Cancer, 37, 4-66.
  26. Puri S, Mangat C, Bhatia V, Kaur AP, Kohli DR (2010). Knowledge of cancer and its risk factors in Chandigarh, India. Int J Epidemiol, 8, 1-7.
  27. Sadjadi A, Malekzadeh R, Derakhshan MH, et al (2003). Cancer occurrence in Ardabil: results of a population-based cancer registry from Iran. Int J Cancer, 107, 113-8.
  28. Sadjadi A, Nouraie M, Mohagheghi MA, et al (2005). Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev, 6, 359-63.
  29. Stemmermann GN, Samloff IM, Nomura AM, et al (1987). Serum pepsinogens I and II and stomach cancer. Clin Chim Acta, 163, 191-8.
  30. Varis K, Sipponen P, Laxen F, et al (2000). Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. Helsinki Gastritis Study Group. Scand J Gastroenterol, 35, 950-6.
  31. Yanaoka K, Oka M, Mukoubayashi C, et al (2008). Cancer highrisk subjects identified by serum pepsinogen tests: outcomes after 10-year follow-up in asymptomatic middle-aged males. Cancer Epidemiol Biomarkers Prev, 17, 838-45.

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