Digestive Diseases and Sciences

, Volume 60, Issue 9, pp 2712–2717 | Cite as

Characterization of Gastric Cardia Tumors: Differences in Helicobacter pylori Strains and Genetic Polymorphisms

  • Débora Menezes da Costa
  • Eliane dos Santos Pereira
  • Isabelle Joyce de Lima Silva-Fernandes
  • Márcia Valéria Pitombeira Ferreira
  • Silvia Helena Barem Rabenhorst
Original Article



Gastric cancer results from a multifactorial process and is one of the most common causes of death worldwide. These tumors can arise in the distal stomach (non-cardia) and in the cardia region, presenting different characteristics and frequency of occurrence worldwide.


To search for differences between tumors of different locations that could explain the presence of cardia tumors, considering Helicobacter pylori strains and genetic polymorphisms.

Materials and Methods

DNA was extracted from gastric adenocarcinoma tissue of 127 patients. Helicobacter pylori genes were detected by PCR, and polymorphisms by PCR–RFLP.


Most of the tumors were located in non-cardia. The genotype 28152GA of XRCC1 showed an increase in risk of cardia tumors. In analysis performed considering gender, women carrying TNF-308GA genotype showed a decreased risk of non-cardia tumors, while in men the decreased risk of non-cardia tumors was associated with TNF-308GG genotype. Genotypes combinations showed that the SNPs RAD51 135G>C, XRCC3 18067C>T, and XRCC1 28152G>A had some combinations more frequent in cardia tumors, with an increased risk. Patients infected by cagE-positive strains presented a positive correlation with non-cardia tumors.


The results showed some susceptibility differences between tumors of different locations. There was an increased risk relationship between three repair enzyme SNPs and cardia tumors, and the G allele of the cytokine gene TNF negatively influenced the development of non-cardia tumors. Helicobacter pylori strains seemed to be different in the cardia region, where they were less virulent than those located in the distal region of the stomach.


Cardia tumors Helicobacter pylori Repair enzymes Interleukins 


Conflict of interest


Supplementary material

10620_2015_3666_MOESM1_ESM.doc (53 kb)
Supplementary material 1 (DOC 53 kb)


  1. 1.
    Globocan, 2012. Available at: http://globocan.iarc.fr/. Accessed July 17, 2014.
  2. 2.
    Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut. 2001;49:347–353.CrossRefGoogle Scholar
  3. 3.
    Tytgat GN, Bartelink H, Bernards R, et al. Cancer of the esophagus and gastric cardia: recent advances. Dis Esophagus. 2004;17:10–26.CrossRefPubMedGoogle Scholar
  4. 4.
    Piazuelo MB, Correa P. Gastric cancer: overview. Colomb Med. 2013;44:192–201.PubMedGoogle Scholar
  5. 5.
    Foster GD, Twell DJ. Plant gene isolation: principles and practice. England: Wiley; 1996.Google Scholar
  6. 6.
    Lage AP, Godfroid E, Fauconnier A, et al. Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive techniques and detection of cagA gene in gastric biopsy specimens. J Clin Microbiol. 1995;33:2752–2756.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Lima VP, Silva-Fernandes IJ, Alves MK, Rabenhorst SH. Prevalence of Helicobacter pylori genotypes (vacA, cagA, cagE and virB11) in gastric cancer in Brazilian’s patients: an association with histopathological parameters. Cancer Epidemiol. 2011;35:32–37.CrossRefGoogle Scholar
  8. 8.
    de Martel C, Ferlay J, Franceschi S, et al. The global burden of cancers attributable to infections in the year 2008: a review and synthetic analysis. Lancet Oncol. 2012;13:607–615.CrossRefPubMedGoogle Scholar
  9. 9.
    Lunn RM, Langlois RG, Hsieh LL, Thompson CL, Bell DA. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res. 1999;59:2557–2561.PubMedGoogle Scholar
  10. 10.
    Duell EJ, Wiencke JK, Cheng TJ, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000;21:965–971.CrossRefPubMedGoogle Scholar
  11. 11.
    Shen H, Xu Y, Qian Y, et al. Polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population. Int J Cancer. 2000;88:601–606.CrossRefPubMedGoogle Scholar
  12. 12.
    Miao X, Zhang X, Zhang L, et al. Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer. Gastroenterology. 2006;131:420–427.CrossRefPubMedGoogle Scholar
  13. 13.
    Ratnasinghe LD, Abnet C, Qiao YL, et al. Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer. Cancer Lett. 2004;216:157–164.CrossRefPubMedGoogle Scholar
  14. 14.
    Yan L, Yanan D, Donglan S, Na W, Rongmiao Z, Zhifeng C. Polymorphisms of XRCC1 gene and risk of gastric cardiac adenocarcinoma. Dis Esophagus. 2009;22:396–401.CrossRefPubMedGoogle Scholar
  15. 15.
    Xue H, Ni P, Lin B, Xu H, Huang G. X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and gastric cancer risk: a HuGE review and meta-analysis. Am J Epidemiol. 2011;173:363–375.CrossRefPubMedGoogle Scholar
  16. 16.
    Chen B, Zhou Y, Yang P, Wu XT. Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis. Mol Biol Rep. 2012;39:1305–1313.CrossRefPubMedGoogle Scholar
  17. 17.
    Poplawski T, Arabski M, Kozirowskaa D, et al. DNA damage and repair in gastric cancer—a correlation with the hOGG1 and RAD51 genes polymorphisms. Mutat Res. 2006;601:83–91.CrossRefPubMedGoogle Scholar
  18. 18.
    Fan XJ, Ren PL, Lu ZJ, Zhao S, Yang XL, Liu J. The study of esophageal cancer risk associated with polymorphisms of DNA damage repair genes XRCC4 and RAD51. Sichuan Da Xue Xue Bao Yi Xue Ban. 2013;44:568–572.PubMedGoogle Scholar
  19. 19.
    Tramacere I, Pelucchi C, Bagnardi V, et al. A meta-analysis on alcohol drinking and esophageal and gastric cardia adenocarcinoma risk. Ann Oncol. 2012;23:287–297.CrossRefPubMedGoogle Scholar
  20. 20.
    Shrivastav M, De Haro LP, Nickoloff JA. Regulation of DNA double-strand break repair pathway choice. Cell Res. 2008;18:134–147.CrossRefPubMedGoogle Scholar
  21. 21.
    Bishop DK, Ear U, Bhattacharyya A, et al. XRCC3 is required for assembly of RAD51 complexes in vivo. J Biol Chem. 1998;21:21482–21488.CrossRefGoogle Scholar
  22. 22.
    Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997;94:3195–3199.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Hansen S, Vollset SE, Derakhshan MH, et al. Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status. Gut. 2007;56:918–925.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Lima VP, Lima MAP, Ferreira MVP, Barros MAP, Rabenhorst SHB. The relationship between Helicobacter pylori genes cagE and virB11 and gastric cancer. Int J Infect Dis. 2010;14:613–617.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Débora Menezes da Costa
    • 1
  • Eliane dos Santos Pereira
    • 1
  • Isabelle Joyce de Lima Silva-Fernandes
    • 1
  • Márcia Valéria Pitombeira Ferreira
    • 1
  • Silvia Helena Barem Rabenhorst
    • 1
  1. 1.Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of MedicineFederal University of CearáFortalezaBrazil

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