Abstract
Background and Aim
The selection of a high-risk group of gastric cancer is important. This study was performed to compare the efficacy of non-invasive gastric cancer screening through the measurement of pepsinogen (PG) I/II ratio and endoscopic screening using histologic criteria (Meining’s risk index for gastric cancer) in Korean patients.
Methods
Included in the study were 460 gastric cancer patients and 460 control cases who underwent upper endoscopy between June 2003 and July 2008 at Seoul National University Bundang Hospital. Serum PG I/II ratio and histologic characteristics were evaluated for each participant. Multivariate logistic regression was performed to compare the predictive power for gastric cancer of both the PG II/I ratio (the inverse form of PG I/II ratio) and the histologic gastric cancer risk index.
Results
A higher PG II/I ratio was significantly associated with a higher risk for gastric cancer (odds ratio of highest quartile for cancer vs. lowest quartile, 3.51; 95% confidence interval, 2.29–5.36) in the multivariate logistic model. The validity (in terms of calibration and discrimination) of the PG-including multivariate logistic model was comparable to the histologic gastric cancer risk index model. The results were similar regardless of the staging of the cancer, Lauren’s histologic classification, and the location of the cancer.
Conclusions
These results suggest that non-invasive measurement of serum PG I/II ratio is as effective as Meining’s histologic gastric cancer risk index in predicting gastric cancer occurrence.
Similar content being viewed by others
References
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
Kunisaki C, Ishino J, Nakajima S, et al. Outcomes of mass screening for gastric carcinoma. Ann Surg Oncol. 2006;13:221–228.
Hosokawa O, Miyanaga T, Kaizaki Y, et al. Decreased death from gastric cancer by endoscopic screening: association with a population-based cancer registry. Scand J Gastroenterol. 2008;43:1112–1115.
Meining A, Bayerdorffer E, Muller P, et al. Gastric carcinoma risk index in patients infected with Helicobacter pylori. Virchows Arch. 1998;432:311–314.
Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer. 2006;9:245–253.
Mizoue T, Yoshimura T, Tokui N, et al. Prospective study of screening for stomach cancer in Japan. Int J Cancer. 2003;106:103–107.
Watabe H, Mitsushima T, Yamaji Y, et al. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut. 2005;54:764–768.
Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology. 2007;133:659–672.
Forman D, Newell DG, Fullerton F, et al. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ. 1991;302:1302–1305.
Ohata H, Kitauchi S, Yoshimura N, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer. 2004;109:138–143.
Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325:1127–1131.
The EUROGAST study group. An international association between Helicobacter pylori infection and gastric cancer. Lancet. 1993;341:1359–1362.
Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789.
Hirata Y, Maeda S, Mitsuno Y, et al. Helicobacter pylori CagA protein activates serum response element-driven transcription independently of tyrosine phosphorylation. Gastroenterology. 2002;123:1962–1971.
Goto T, Haruma K, Kitadai Y, et al. Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients. Clin Cancer Res. 1999;5:1411–1415.
Kodoi A, Yoshihara M, Sumii K, Haruma K, Kajiyama G. Serum pepsinogen in screening for gastric cancer. J Gastroenterol. 1995;30:452–460.
Borch K, Axelsson CK, Halgreen H, Damkjaer Nielsen MD, Ledin T, Szesci PB. The ratio of pepsinogen A to pepsinogen C: a sensitive test for atrophic gastritis. Scand J Gastroenterol. 1989;24:870–876.
Samloff IM. Cellular localization of group I pepsinogens in human gastric mucosa by immunofluorescence. Gastroenterology. 1971;61:185–188.
Samloff IM, Liebman WM. Cellular localization of the group II pepsinogens in human stomach and duodenum by immunofluorescence. Gastroenterology. 1973;65:36–42.
Samloff IM, Varis K, Ihamaki T, Siurala M, Rotter JI. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology. 1982;83:204–209.
Miki K, Ichinose M, Kakei N, et al. The clinical application of the serum pepsinogen I and II levels as a mass screening method for gastric cancer. Adv Exp Med Biol. 1995;362:139–143.
Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–1181.
Kajitani T. The general rules for the gastric cancer study in surgery and pathology. Part I. clinical classification. Jpn J Surg. 1981;11:127–139.
Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.
Loffeld RJ, Stobberingh E, Flendrig JA, Arends JW. Helicobacter pylori in gastric biopsy specimens. Comparison of culture, modified Giemsa stain, and immunohistochemistry. A retrospective study. J Pathol. 1991;165:69–73.
Kim SY, Ahn JS, Ha YJ, et al. Serodiagnosis of Helicobacter pylori infection in Korean patients using enzyme-linked immunosorbent assay. J Immunoassay. 1998;19:251–270.
Kullavanijaya P, Thong-Ngam D, Hanvivatvong O, Nunthapisud P, Tangkijvanich P, Suwanagool P. Analysis of eight different methods for the detection of Helicobacter pylori infection in patients with dyspepsia. J Gastroenterol Hepatol. 2004;19:1392–1396.
Andersen LP, Kiilerick S, Pedersen G, et al. An analysis of seven different methods to diagnose Helicobacter pylori infections. Scand J Gastroenterol. 1998;33:24–30.
Karnes WE Jr, Samloff IM, Siurala M, et al. Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Gastroenterology. 1991;101:167–174.
Kokkola A, Kosunen TU, Puolakkainen P, et al. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS. 2003;111:619–624.
Kang JM, Kim N, Yoo JY, et al. The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea. Helicobacter. 2008;13:146–156.
Tashiro A, Sano M, Kinameri K, Fujita K, Takeuchi Y. Comparing mass screening techniques for gastric cancer in Japan. World J Gastroenterol. 2006;12:2874–4873.
Leung WK, Wu MS, Kakugawa Y, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–287.
Imagawa S, Yoshihara M, Ito M, et al. Evaluation of gastric cancer risk using topography of histological gastritis: a large-scaled cross-sectional study. Dig Dis Sci. 2008;53:1818–1823.
Mabogunje OA, Subbuswamy SG, Lawrie JH. The two histological types of gastric carcinoma in northern Nigeria. Gut. 1978;19:425–429.
Di Mario F, Cavallaro LG, Moussa AM, et al. Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium. Dig Dis Sci. 2006;51:1791–1795.
Asaka M, Kimura T, Kudo M, et al. Relationship of Helicobacter pylori to serum pepsinogens in an asymptomatic Japanese population. Gastroenterology. 1992;102:760–766.
Korstanje A, van Eeden S, Offerhaus JA, et al. Comparison between serology and histology in the diagnosis of advanced gastric body atrophy: a study in a Dutch primary community. J Clin Gastroenterol. 2008;42:18–22.
Bodger K, Wyatt JI, Heatley RV. Variation in serum pepsinogens with severity and topography of Helicobacter pylori-associated chronic gastritis in dyspeptic patients referred for endoscopy. Helicobacter. 2001;6:216–224.
Yim JY, Kim N, Choi SH, et al. Seroprevalence of Helicobacter pylori in South Korea. Helicobacter. 2007;12:333–340.
Acknowledgments
This study was supported by the Korean Health 21 R & D Project, Ministry of Health & Welfare, Republic of Korea (#A060266).
Conflict of interest and financial support
None of the authors had conflicts of interest that potentially influence the described research, and there was no external financial support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kwak, M.S., Kim, N., Lee, H.S. et al. Predictive Power of Serum Pepsinogen Tests for the Development of Gastric Cancer in Comparison to the Histologic Risk Index. Dig Dis Sci 55, 2275–2282 (2010). https://doi.org/10.1007/s10620-010-1181-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-010-1181-x