Cancer Causes & Control

, Volume 24, Issue 2, pp 241–248 | Cite as

The utility of serologic tests as biomarkers for Helicobacter pylori-associated precancerous lesions and gastric cancer varies between Latin American countries

  • L. Flores-Luna
  • M. Camorlinga-Ponce
  • G. Hernandez-Suarez
  • E. Kasamatsu
  • M. E. Martínez
  • R. Murillo
  • E. Lazcano
  • J. Torres
Original paper
First Online:
Received:
Accepted:

Abstract

Purpose

Currently, studies on serologic diagnosis of Helicobacter pylori-associated gastric cancer (GC) in Latin America are scarce. The aim of the present study was to evaluate the association between H. pylori serology tests in patients with early precancerous lesions or GC, when compared with non-atrophic gastritis in Colombia, Paraguay, and Mexico, three countries in Latin America with a high prevalence of H. pylori infection but contrasting rates of GC mortality.

Methods

Gastric biopsies and blood samples were obtained from patients attending the gastroenterology or oncology services of hospitals in the three participating countries. IgG antibodies against H. pylori whole-cell antigens and CagA were tested in 1,117 sera using an enzyme-linked immunoabsorbent assay.

Results

Positive and significant associations were shown for H. pylori seropositivity and preneoplastic lesions in Mexico (OR 2.0; 95 % CI 1.1–3.4) but not in Colombia (OR 1.2; 95 % CI 0.6–2.1) or Paraguay (OR 1.5; 95 % CI 0.6–3.2); no significant associations were shown for GC in any country. CagA seropositivity was associated with preneoplasic lesions in all three countries (ORs = 2.1, 3.0, and 3.1 for Mexico, Colombia, and Paraguay, respectively), and with GC only in Colombia (OR 4.3; 95 % CI 2.1–9.2).

Conclusions

In countries of Latin America, the IgG CagA test might be a useful biomarker for patients with gastric preneoplastic lesions and for those at risk of developing gastric cancer.

Keywords

Helicobacter pylori CagA Gastric cancer Gastric preneoplastic lesions Serologic biomarkers 
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Notes

Acknowledgments

This work was supported by CONACYT, México (grant No. 69450), and by Instituto Nacional de Cancerología, Colombia (Grant No. 1044-06). JT is a recipient of a exclusivity scholarship from Fundación IMSS, México.

References

  1. 1.
    Lochhead P, El-Omar EM (2008) Gastric cancer. Br Med Bull 85:87–100PubMedCrossRefGoogle Scholar
  2. 2.
    Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM (2010) The global burden of cancer: priorities for prevention. Carcinogenesis 31:100–110PubMedCrossRefGoogle Scholar
  3. 3.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRefGoogle Scholar
  4. 4.
    Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J et al (2009) Recent patterns in gastric cancer: a global overview. Int J Cancer 125:666–673PubMedCrossRefGoogle Scholar
  5. 5.
    Hatakeyama M (2011) Anthropological and clinical implications for the structural diversity of the Helicobacter pylori CagA oncoprotein. Cancer Sci 102:36–43PubMedCrossRefGoogle Scholar
  6. 6.
    Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M et al (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA 105:1003–1008PubMedCrossRefGoogle Scholar
  7. 7.
    Brenner H, Arndt V, Stegmaier C, Ziegler H, Rothenbacher D (2004) Is Helicobacter pylori infection a necessary condition for noncardia gastric cancer? Am J Epidemiol 159:252–258PubMedCrossRefGoogle Scholar
  8. 8.
    Suriani R, Colozza M, Cardesi E, Mazzucco D, Marino M et al (2008) CagA and VacA Helicobacter pylori antibodies in gastric cancer. Can J Gastroenterol 22:255–258PubMedGoogle Scholar
  9. 9.
    Blaser MJ, Perez–Perez GI, Kleanthous H, Cover TL, Peek RM et al (1995) Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55:2111–2115PubMedGoogle Scholar
  10. 10.
    Cover TL, Glupczynski Y, Lage AP, Burette A, Tummuru MK et al (1995) Serologic detection of infection with cagA+ Helicobacter pylori strains. J Clin Microbiol 33:1496–1500PubMedGoogle Scholar
  11. 11.
    Mattar R, Marques SB, Monteiro Mdo S, Dos Santos AF, Iriya K et al (2007) Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic ulcer disease development in Brazil. J Med Microbiol 56:9–14PubMedCrossRefGoogle Scholar
  12. 12.
    Shiota S, Matsunari O, Watada M, Yamaoka Y (2010) Serum Helicobacter pylori CagA antibody as a biomarker for gastric cancer in east-Asian countries. Future Microbiol 5:1885–1893PubMedCrossRefGoogle Scholar
  13. 13.
    Webb PM, Crabtree JE, Forman D (1999) Gastric cancer, cytotoxin-associated gene A-positive Helicobacter pylori, and serum pepsinogens: an international study. The Eurogst Study Group. Gastroenterology 116:269–276PubMedCrossRefGoogle Scholar
  14. 14.
    Camorlinga-Ponce M, Flores-Luna L, Lazcano-Ponce E, Herrero R, Bernal-Sahagun F et al (2008) Age and severity of mucosal lesions influence the performance of serologic markers in Helicobacter pylori-associated gastroduodenal pathologies. Cancer Epidemiol Biomarkers Prev 17:2498–2504PubMedCrossRefGoogle Scholar
  15. 15.
    Camorlinga-Ponce M, Torres J, Perez–Perez G, Leal-Herrera Y, Gonzalez-Ortiz B et al (1998) 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 93:1264–1270PubMedCrossRefGoogle Scholar
  16. 16.
    Ferreccio C, Rollán A, Harris PR, Serrano C, Gederlini A et al (2007) Gastric cancer is related to early Helicobacter pylori infection in a high-prevalence country. Cancer Epidemiol Biomarkers Prev 16:662–667PubMedCrossRefGoogle Scholar
  17. 17.
    Plummer M, van Doorn LJ, Franceschi S, Kleter B, Canzian F et al (2007) Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. J Natl Cancer Inst 99:1328–1334PubMedCrossRefGoogle Scholar
  18. 18.
    Camargo MC, Yepez MC, Ceron C, Guerrero N, Bravo LE et al (2004) Age at acquisition of Helicobacter pylori infection: comparison of two areas with contrasting risk of gastric cancer. Helicobacter 9:262–270PubMedCrossRefGoogle Scholar
  19. 19.
    Kasamatsu E, Bravo LE, Bravo JC, Aguirre-Garcia J, Flores-Luna L et al (2010) Reproducibility of histopathologic diagnosis of precursor lesions of gastric carcinoma in three Latin American countries. Salud Publica Mex 52:386–390PubMedCrossRefGoogle Scholar
  20. 20.
    Torres J, Camorlinga-Ponce M, Perez–Perez G, Munoz L, Munoz O (2002) Specific serum immunoglobulin G response to urease and CagA antigens of Helicobacter pylori in infected children and adults in a country with high prevalence of infection. Clin Diagn Lab Immunol 9:97–100PubMedGoogle Scholar
  21. 21.
    Hsu PI, Lai KH, Tseng HH, Liu YC, Yen MY et al (1997) Correlation of serum immunoglobulin G Helicobacter pylori antibody titers with histologic and endoscopic findings in patients with dyspepsia. J Clin Gastroenterol 25:587–591PubMedCrossRefGoogle Scholar
  22. 22.
    Yanaoka K, Oka M, Yoshimura N, Mukoubayashi C, Enomoto S et al (2008) Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Int J Cancer 123:917–926PubMedCrossRefGoogle Scholar
  23. 23.
    Chen TS, Li FY, Chang FY, Lee SD (2002) Immunoglobulin G antibody against Helicobacter pylori: clinical implications of levels found in serum. Clin Diagn Lab Immunol 9:1044–1048PubMedGoogle Scholar
  24. 24.
    Graham DY, Genta RM, Graham DP, Crabtree JE (1996) Serum CagA antibodies in asymptomatic subjects and patients with peptic ulcer: lack of correlation of IgG antibody in patients with peptic ulcer or asymptomatic Helicobacter pylori gastritis. J Clin Pathol 49:829–832PubMedCrossRefGoogle Scholar
  25. 25.
    Bedoya A, Garay J, Sanzon F, Bravo LE, Bravo JC et al (2003) Histopathology of gastritis in Helicobacter pylori-infected children from populations at high and low gastric cancer risk. Hum Pathol 34:206–213PubMedCrossRefGoogle Scholar
  26. 26.
    Munoz L, Camorlinga M, Hernandez R, Giono S, Ramon G et al (2007) Immune and proliferative cellular responses to Helicobacter pylori infection in the gastric mucosa of Mexican children. Helicobacter 12:224–230PubMedCrossRefGoogle Scholar
  27. 27.
    Kokkola A, Kosunen TU, Puolakkainen P, Sipponen P, Harkonen M et al (2003) Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS 111:619–624PubMedCrossRefGoogle Scholar
  28. 28.
    Klaamas K, Held M, Wadstrom T, Lipping A, Kurtenkov O (1996) IgG immune response to Helicobacter pylori antigens in patients with gastric cancer as defined by ELISA and immunoblotting. Int J Cancer 67:1–5PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang L, Blot WJ, You WC, Chang YS, Kneller RW et al (1996) Helicobacter pylori antibodies in relation to precancerous gastric lesions in a high-risk Chinese population. Cancer Epidemiol Biomarkers Prev 5:627–630PubMedGoogle Scholar
  30. 30.
    Con SA, Con-Wong R, Con-Chin GR, Con-Chin VG, Takeuchi H et al (2007) Serum pepsinogen levels, Helicobacter pylori CagA Status, and cytokine gene polymorphisms associated with gastric premalignant lesions in Costa Rica. Cancer Epidemiol Biomarkers Prev 16:2631–2636PubMedCrossRefGoogle Scholar
  31. 31.
    Meine GC, Rota C, Dietz J, Sekine S, Prolla JC (2011) Relationship between cagA-positive Helicobacter pylori infection and risk of gastric cancer: a case control study in Porto Alegre, RS, Brazil. Arq Gastroenterol 48:41–45PubMedGoogle Scholar
  32. 32.
    Tatemichi M, Hamada GS, Nishimoto IN, Kowalski LP, Iriya K et al (2003) Ethnic difference in serology of Helicobacter pylori CagA between Japanese and non-Japanese Brazilians for non-cardia gastric cancer. Cancer Sci 94:64–69PubMedCrossRefGoogle Scholar
  33. 33.
    Nomura AM, Lee J, Stemmermann GN, Nomura RY, Perez–Perez GI et al (2002) Helicobacter pylori CagA seropositivity and gastric carcinoma risk in a Japanese American population. J Infect Dis 186:1138–1144PubMedCrossRefGoogle Scholar
  34. 34.
    Peek RM Jr, Miller GG, Tham KT, Perez–Perez GI, Zhao X et al (1995) Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest 73:760–770PubMedGoogle Scholar
  35. 35.
    Pan ZJ, van der Hulst RW, Feller M, Xiao SD, Tytgat GN et al (1997) Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia. J Clin Microbiol 35:1344–1347PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • L. Flores-Luna
    • 1
  • M. Camorlinga-Ponce
    • 2
  • G. Hernandez-Suarez
    • 3
  • E. Kasamatsu
    • 4
  • M. E. Martínez
    • 5
  • R. Murillo
    • 3
  • E. Lazcano
    • 1
  • J. Torres
    • 2
  1. 1.Centro de Investigación en Salud PoblacionalInstituto Nacional de Salud PúblicaCuernavacaMexico
  2. 2.Instituto Mexicano del Seguro SocialUnidad de Investigación en Enfermedades InfecciosasMexicoMexico
  3. 3.Grupo Investigación EpidemiológicaInstituto Nacional de CancerologíaBogotáColombia
  4. 4.Instituto de Investigaciones en Ciencias de la SaludUniversidad Nacional de AsunciónAsunciónParaguay
  5. 5.Moores UCSD Cancer CenterUniversity of California, San DiegoLa JollaUSA

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