Serum pepsinogen levels and gastric atrophy diagnostic capacity in different Colombian populations
Keywords:
Pepsinogens, Helicobacter pylori, Atrophic gastritisAbstract
Objective: To characterize levels of pepsinogen and evaluate the discrimination ability of pepsinogen I (PGI) and the PGI/ pepsinogen II (PGII) ratio for the serological diagnosis of gastric atrophy in different Colombian populations.
Methods: A total 600 subjects without gastric symptoms participated and 544 samples from patients with gastric symptomatology were analyzed from different populations with opposing risks to gastric cancer. A blood sample was taken from all participants; a gastric antrum and body biopsy for the initial diagnosis of gastroduodenal lesions was obtained from the patients. The levels of pepsinogen and Helicobacter pylori serology were estimated with ELISA. Statistical analyses included Kruskal -Wallis and Mann -Whitney test, ROC curve and diagnostic values.
Results: The levels of PGI and PGI / PGII differ by risk area of origin. Levels of PGI, PGII and PGI / PGII decreased with increasing severity of histological diagnosis (P < .005), as with the severity of atrophy and multifocal localization (P ≤.001). The PGI ≤ 86.68 and PGI / PGII ≤ 3.19 with an area under the curve of 0.76 identified patients with severe multifocal atrophy, positive serology for H. pylori, and from the high risk area, with a sensitivity of 77.5% and specificity of 71.74%.
Conclusion: The results suggest that PGI levels together with PGI / PGII ratios and positive serology for H. pylori could be considered for the detection of severe atrophy in high-risk areas. Further studies are needed in high-risk populations
Author Biographies
Teresa Martínez, Instituto Nacional de Cancerología
Grupo de Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá, D.C. Colombia
María Mercedes Bravo, Instituto Nacional de Cancerología
Grupo de Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
Diana Leandra Núñez, Instituto Nacional de Cancerología
Grupo de Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá, D.C. Colombia
Gustavo A. Hernández, Instituto Nacional de Cancerología
Grupo de Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá, D.C. Colombia
Margarita Camorlinga, Hospital de Pediatría CMN siglo XXI
Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría CMN siglo XXI, Ciudad de México, México
References
Ferley J, Shin HR, Bray F, Mathers C, Parkin DM. Globocan 2008 v 1.2 Cancer incidence and mortality worldwide: IARC CancerBase No.10. International Agency for Research on Cancer. 2013, http://globocan iarc fr 2013 August 20 Available from: URL: http://globocan.iarc.fr.
Piñeros M, Pardo C, Gamboa O, Hernandez G. Atlas de mortalidad por cáncer en Colombia. 3 ed. ed. Bogotá: Instituto Nacional de Cancerologia E.S.E.; Instituto Geográfico Agustin Codazzi; 2010.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process-First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention 1. Cancer Res. 1992;52:6735-40.
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345: 784-9.
https://doi.org/10.1056/NEJMoa001999
Flores-Luna L, Camorlinga-Ponce M, Hernandez-Suarez G, Kasamatsu E, Martinez ME, Murillo R, et al. The utility of serologic tests as biomarkers for Helicobacter pylori-associated precancerous lesions and gastric cancer varies between Latin American countries. Cancer Causes Control. 2013;24:241-8.
https://doi.org/10.1007/s10552-012-0106-8
Martinez T, Hernández G, Bravo MM, Trujillo E, Quiroga A, Robayo JC, et al. Polimorfismos geneticos de interleucinas IL-1B-511, IL-1RN IL-10, factor de necrosis tumoral fd-308 e infeccion por Helicobacter pylori CagA positivo en cancer gástrico y ulcera duodenal en diferentes poblaciones en Colombia. Revista Colombiana de Cancerología. 2011;15:85-97.
https://doi.org/10.1016/S0123-9015(11)70071-3
Bravo L, Cortés A, Carrascal E, Jaramillo, García LS, Bravo P, et al. Helicobacter pylori: patología y prevalencia en biopsias gástricas en Colombia. Colombia Médica. 2003;34: 124-31.
Broutet N, Plebani M, Sakarovitch C, Sipponen P, Megraud F. Pepsinogen A, pepsinogen C and gastrin as markers of atrophic chronic gastritis in European dyspeptics. Br J Cancer. 2003;88:1239-47.
https://doi.org/10.1038/sj.bjc.6600877
Con SA, Con-Wong R, Con-Chin GR, Con-Chin VG, Takeuchi H, Valerin AL, et al. Serum pepsinogen levels. Helicobacter pylori CagA Status, and cytokine gene polymorphisms associated with gastric premalignant lesions in Costa Rica. Cancer Epidemiol Biomarkers Prev. 2007;16:2631-6.
https://doi.org/10.1158/1055-9965.EPI-07-0215
Dinis-Ribeiro M, Yamaki G, Miki K, Costa-Pereira A, Matsukawa M, Kurihara M. Meta-analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophic gastritis screening. J Med Screen. 2004;11:141-7.
https://doi.org/10.1258/0969141041732184
Miki K, Morita M, Sasajima M, Hoshina R, Kanda E, Urita Y. Usefulness of gastric cancer screening using the serum pepsinogen test method. Am J Gastroenterol. 2003;98:735-9.
https://doi.org/10.1111/j.1572-0241.2003.07410.x
Watabe H, Mitsushima T, Yamaji Y, Okamoto M, Wada R, Kokubo T, et al. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut. 2005;54:764-8.
https://doi.org/10.1136/gut.2004.055400
Ley C, Mohar A, Guarner J, Herrera-Goepfert R, Figueroa LS, Halperin D, et al. Screening markers for chronic atrophic gastritis in Chiapas. Mexico Cancer Epidemiol Biomarkers Prev. 2001;10:107-12.
Ricci C, Vakil N, Rugge M, Gatta L, Perna F, Osborn JF, et al. Serological markers for gastric atrophy in asymptomatic patients infected with Helicobacter pylori. Am J Gastroenterol. 2004;99:1910-5.
https://doi.org/10.1111/j.1572-0241.2004.40614.x
Kang JM, Kim N, Yoo JY, Park YS, Lee DH, Kim HY, et al. The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea. Helicobacter. 2008;13:146-56.
https://doi.org/10.1111/j.1523-5378.2008.00592.x
Sipponen P, Ranta P, Helske T, Kaariainen I, Maki T, Linnala A, et al. Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an observational case-control study. Scand J Gastroenterol. 2002;37:785-91.
https://doi.org/10.1080/gas.37.7.785.791
Haj-sheykholeslami A, Rakhshani N, Amirzargar A, Rafiee R, Shahidi SM, Nikbin B, et al. 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. 2008;6:174-9.
https://doi.org/10.1016/j.cgh.2007.11.016
Yakut M, Ormeci N, Erdal H, Keskin O, Karayel Z, Tutkak H, et al. The association between precancerous gastric lesions and serum pepsinogens, serum gastrin, vascular endothelial growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and Helicobacter pylori Cag A status. Clin Res Hepatol Gastroenterol. 2013;37:302-11.
https://doi.org/10.1016/j.clinre.2012.09.013
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;20:1161-81.
https://doi.org/10.1097/00000478-199610000-00001
Rugge M, Correa P, Dixon MF, Hattori T, Leandro G, Lewin K, et al. Gastric dysplasia: the Padova international classification. Am J Surg Pathol. 2000;24:167-76.
https://doi.org/10.1097/00000478-200002000-00001
Lauren P. Histogenesis of intestinal and diffuse types of gastric carcinoma. Scand J Gastroenterol Suppl. 1991;180:160-4.
https://doi.org/10.3109/00365529109093194
Camorlinga-Ponce M, Torres J, Perez-Perez G, Leal-Herrera Y, Gonzalez-Ortiz B, Madrazo dlG, et al. Validation of a serologic test for the diagnosis of Helicobacter pylori infection and the immune response to urease and CagA in children. Am J Gastroenterol. 1998;93:1264-70.
https://doi.org/10.1111/j.1572-0241.1998.00407.x
Camorlinga-Ponce M, Flores-Luna L, Lazcano-Ponce E, Herrero R, Bernal-Sahagun F, Abdo-Francis JM, et al. Age and severity of mucosal lesions influence the performance of serologic markers in Helicobacter pylori-associated gastroduodenal pathologies. Cancer Epidemiol Biomarkers Prev. 2008;17:2498-504.
https://doi.org/10.1158/1055-9965.EPI-08-0289
Sun LP, Gong YH, Wang L, Yuan Y. Serum pepsinogen levels and their influencing factors: a population-based study in 6990 Chinese from North China. World J Gastroenterol. 2007;13:6562-7.
https://doi.org/10.3748/wjg.v13.i48.6562
Li P, He C, Sun L, Dong N, Yuan Y. Pepsinogen I and II expressions in situ and their correlations with serum pesignogen levels in gastric cancer and its precancerous disease. BMC Clin Pathol. 2013;13:22.
https://doi.org/10.1186/1472-6890-13-22
Derakhshan MH, El-Omar E, Oien K, Gillen D, Fyfe V, Crabtree JE, et al. Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected with Helicobacter pylori. J Clin Pathol. 2006;59:1293-9.
https://doi.org/10.1136/jcp.2005.036111
Shikata K, Ninomiya T, Yonemoto K, Ikeda F, Hata J, Doi Y, et al. Optimal cutoff value of the serum pepsinogen level for prediction of gastric cancer incidence: the Hisayama Study. Scand J Gastroenterol. 2012;47:669-75.
https://doi.org/10.3109/00365521.2012.658855
Lorente S, Doiz O, Trinidad SM, Castillo J, Lanas A. Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells. Gut. 2002;50:13-8.
https://doi.org/10.1136/gut.50.1.13
Germana B, Di MF, Cavallaro LG, Moussa AM, Lecis P, Liatoupolou S, et al. Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacterpylori antibodies in the management of dyspeptic patients in primary care. Dig Liver Dis. 2005;37:501-8.
https://doi.org/10.1016/j.dld.2005.01.016
Kim HY, Kim N, Kang JM, Park YS, Lee DH, Kim YR, et al. Clinical meaning of pepsinogen test and Helicobacter pylori serology in the health check-up population in Korea. Eur J Gastroenterol Hepatol. 2009;21:606-12.
https://doi.org/10.1097/MEG.0b013e3283086757
Kiyohira K, Yoshihara M, Ito M, Haruma K, Tanaka S, Chayama K. Serum pepsinogen concentration as a marker of Helicobacter pyloriinfection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels. J Gastroenterol. 2003;38:332-8.
https://doi.org/10.1007/s005350300060
Vaananen H, Vauhkonen M, Helske T, Kaariainen I, Rasmussen M, Tunturi-Hihnala H, et al. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol. 2003;15:885-91.
https://doi.org/10.1097/00042737-200308000-00009
Mohamadkhani A, Darvish MS, Salmanroghani H, Allafsghari A, Yazdanbod A, Mirzaei M, et al. Are the serum biomarkers pepsinogen I and II good predictors for the detection of subjects with atrophic gastritis in areas that have different gastric cancer incidence? Arch Iran Med. 2013;16:208-12.
Iijima K, Ohara S, Koike T, Sekine H, Shimosegawa T. Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender. Scand J Gastroenterol. 2004;39:709-16.
https://doi.org/10.1080/00365520410005911
Di MF, Cavallaro LG, Moussa AM, Caruana P, Merli R, Maini A, et al. Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium. Dig Dis Sci. 2006;51:1791-5.
https://doi.org/10.1007/s10620-006-9206-1
Weck MN, Brenner H. Prevalence of chronic atrophic gastritis in different parts of the world. Cancer Epidemiol Biomarkers Prev. 2006;15:1083-94.
https://doi.org/10.1158/1055-9965.EPI-05-0931
Lanas A, Hirschowitz BI. Influence of smoking on basal and on vagally and maximally stimulated gastric acid and pepsin secretion. Scand J Gastroenterol. 1992;27:208-12.
https://doi.org/10.3109/00365529208999950
Kodoman N, Pazos A, Schneider BG, Piazuelo MB, Mera R, Sobota RS, et al. Human and Helicobacter pylori coevolution shapes the risk of gastric disease. PNAS. 2013.
Zheng KC, Aoki K, Li XQ, Lin SG, Wu BS, Zhong WL, et al. Serum pepsinogens, gastrin-17 and Helicobacter pylori antibody in the residents of two cities in china with distinct mortality rates of gastric cancer. Tohoku J Exp Med. 2012;228:289-94.
https://doi.org/10.1620/tjem.228.289
Cao Q, Ran ZH, Xiao SD. Screening of atrophic gastritis and gastric cancer by serum pepsinogen, gastrin-17 and Helicobacter pylori immunoglobulin G antibodies. J Dig Dis. 2007;8:15-22.
https://doi.org/10.1111/j.1443-9573.2007.00271.x
Kato I, Miki K, Munoz N, Vivas JH, Lopez G, Peraza S, et al. Determinants of plasma pepsinogen levels in a population at high risk for stomach cancer in Venezuela. Int J Cancer. 1995;62:512-8.
https://doi.org/10.1002/ijc.2910620504
Kikuchi R, Abe Y, Iijima K, Koike T, Ara N, Uno K, et al. 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. 2011;223:35-44.
https://doi.org/10.1620/tjem.223.35
Abnet CC, Zheng W, Ye W, Kamangar F, Ji BT, Persson C, et al. Plasma pepsinogens, antibodies against Helicobacter pylori, and risk of gastric cancer in the Shanghai Women's Health Study Cohort. Br J Cancer. 2011;104:1511-6.
https://doi.org/10.1038/bjc.2011.77
Martinez T, Hernandez-Suarez G, Bravo MM, Trujillo E, Pérez García J, Robayo JC, et al. Lesiones preneoplásicas gástricas en pacientes colombianos: asociación de polimorfismos genéticos IL-1B-511, IL-1RN, IL-10-819 IL-10-1082, factor de necrosis tumoral á-308 y anticuerpos IgG hacia CagA de Helicobacter pylori. Revista Colombiana de Cancerologia. 2014;18.
https://doi.org/10.1016/S0123-9015(14)70220-3
Naylor GM, Gotoda T, Dixon M, Shimoda T, Gatta L, Owen R, et al. Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients. Gut. 2006;55:1545-52.
https://doi.org/10.1136/gut.2005.080358
Graham DY, Nurgalieva ZZ, El-Zimaity HM, Opekun AR, Campos A, Guerrero L, et al. Noninvasive versus histologic detection of gastric atrophy in a Hispanic population in North America. Clin Gastroenterol Hepatol. 2006;4:306-14.
https://doi.org/10.1016/j.cgh.2005.11.003
Rollan A, Ferreccio C, Gederlini A, Serrano C, Torres J, Harris P. Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer. World J Gastroenterol. 2006;12:7172-8.
https://doi.org/10.3748/wjg.v12.i44.7172
Rugge M, Meggio A, Pennelli G, Piscioli F, Giacomelli L, De PG, et al. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-6.
https://doi.org/10.1136/gut.2006.106666
Storskrubb T, Aro P, Ronkainen J, Sipponen P, Nyhlin H, Talley NJ, et al. Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: The Kalixanda study. Scand J Gastroenterol. 2008;43:1448-55.
https://doi.org/10.1080/00365520802273025
Nasrollahzadeh D, Aghcheli K, Sotoudeh M, Shakeri R, Persson EC, Islami F, et al. Accuracy and cut-off values of pepsinogens I, II and gastrin 17 for diagnosis of gastric fundic atrophy: influence of gastritis. PLoS One. 2011;6:e26957.
https://doi.org/10.1371/journal.pone.0026957
Brenner H, Rothenbacher D, Weck MN. Epidemiologic findings on serologically defined chronic atrophic gastritis strongly depend on the choice of the cutoff-value. Int J Cancer. 2007;121:2782-6.
Fernández J, de Aretxabala X, Santander R, Sabah S, Maira J, Navarro A, et al. Detección de lesiones prenoplásicas gástricas mediante niveles séricos de pepsinógeno en población chilena. Rev Méd Chile. 2007;135:1519-25.
https://doi.org/10.4067/S0034-98872007001200003
Oishi Y, Kiyohara Y, Kubo M, Tanaka K, Tanizaki Y, Ninomiya T, et al. The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study. Am J Epidemiol. 2006;163:629-37.
https://doi.org/10.1093/aje/kwj088
Lomba-Viana R, Dinis-Ribeiro M, Fonseca F, Vieira AS, Bento MJ, Lomba-Viana H. Serum pepsinogen test for early detection of gastric cancer in a European country. Eur J Gastroenterol Hepatol. 2012;24:37-41.
https://doi.org/10.1097/MEG.0b013e32834d0a0a
Shimoyama T, Aoki M, Sasaki Y, Matsuzaka M, Nakaji S, Fukuda S. ABC screening for gastric cancer is not applicable in a Japanese population with high prevalence of atrophic gastritis. Gastric Cancer. 2012;15:331-4.
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