Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Serum 8 Hydroxydeoxyguanosine and Cytotoxin Associated Gene A as Markers for Helicobacter pylori Infection

  • Yeniova, Abdullah Ozgur (Gastroenterology, Kecioren Teaching and Research Hospital) ;
  • Uzman, Metin (Gastroenterology, Kecioren Teaching and Research Hospital) ;
  • Kefeli, Ayse (Gastroenterology, Kecioren Teaching and Research Hospital) ;
  • Basyigit, Sebahat (Gastroenterology, Kecioren Teaching and Research Hospital) ;
  • Ata, Naim (Internal Medicine, Kecioren Teaching and Research Hospital) ;
  • Dal, Kursat (Internal Medicine, Kecioren Teaching and Research Hospital) ;
  • Guresci, Servet (Pathology, Kecioren Teaching and Research Hospital) ;
  • Nazligul, Yasar (Gastroenterology, Kecioren Teaching and Research Hospital)
  • Published : 2015.08.03
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Helicobacter pylori (H.pylori) is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomas and mucosa associated tissue lymphomas. Cytotoxin associated gene A (CagA) is one of the virulence factors of H.pylori. It is hypothesized that reactive oxygen species (ROS) play roles in H.pylori associated disease especially in development of gastric adenocarcinoma. Individuals infected with H.pylori bearing CagA produce more ROS than others. 8-hydroxydeoxyguanosine (8OHdG) is an in vitro marker of DNA damage and oxidative stress. The aim of this study was to investigate the relationship between 8OHdG level, H.pylori infection and CagA and alterations of serum 8OHdG level after H.pylori eradication. Materials and Methods: Patients admitted with dyspeptic complaints and upper gastrointestinal endoscopy were assessed. H.pylori was determined from histopathology of specimens. Serum 8OHdG levels of three groups (H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive) were compared. Patients with H.pylori infection received eradication therapy. Serum 8OHdG levels pretreatment and posttreatment were also compared. Results: In total, 129 patients (M/F, 57/72) were enrolled in the study. Serum 8OHdG level of H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive groups were significantly different ($5.77{\pm}1.35ng/ml$, $5.43{\pm}1.14ng/ml$ and $7.57{\pm}1.25ng/ml$ respectively, p=0.05). Furthermore, eradication therapy reduced serum 8OHdG level ($6.10{\pm}1.54ng/ml$ vs $5.55{\pm}1.23ng/ml$, p=0.05). Conclusions: Individuals infected with H.pylori bearing CagA strains have the highest serum 8OHdG level and eradication therapy decreases the serum 8OHdG level. To the best of our knowledge this is the first study that evaluated the effect of CagA virulence factor on serum 8OHdG level and the effect of eradication therapy on serum 8OHdG levels together. Eradication of CagA bearing H.pylori may prevent gastric adenocarcinoma by decreasing ROS. 8OHdG level may thus be a good marker for prevention from gastric adenocarcinoma.

Keywords

References

  1. Ames BN, Gold LS (1990). Too many rodent carcinogens: mitogenesis increases mutagenesis. Science, 249, 970-1. https://doi.org/10.1126/science.2136249
  2. Calvino Fernandez M, Parra Cid T (2010). H. pylori and mitochondrial changes in epithelial cells. The role of oxidative stress. Rev Esp Enferm Dig, 102, 41-50.
  3. Davies GR, Banatvala N, Collins CE, et al (1994). Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa. Scand J Gastroenterol, 29, 419-24. https://doi.org/10.3109/00365529409096832
  4. Ernst PB, Gold BD (2000). The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol, 54, 615-40. https://doi.org/10.1146/annurev.micro.54.1.615
  5. Everett SM, White KL, Drake IM, et al (2002). The effect of Helicobacter pylori infection on levels of DNA damage in gastric epithelial cells. Helicobacter, 7, 271-80. https://doi.org/10.1046/j.1523-5378.2002.00098.x
  6. Farinati F, Cardin R, Russo VM, et al (2003). Helicobacter pylori CagA status, mucosal oxidative damage and gastritis phenotype: a potential pathway to cancer? Helicobacter, 8, 227-34. https://doi.org/10.1046/j.1523-5378.2003.00149.x
  7. Ferlay J, Soerjomataram I, Dikshit R, et al (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136, 359-86. https://doi.org/10.1002/ijc.29210
  8. Figura N, Valassina M, Roviello F, et al (2000). Helicobacter pylori cagA and vacA types and gastric carcinoma. Dig Liver Dis, 32, 182-3. https://doi.org/10.1016/S1590-8658(00)80272-8
  9. Hahm KB, Lee KJ, Choi SY, et al (1997). Possibility of chemoprevention by the eradication of Helicobacter pylori: oxidative DNA damage and apoptosis in H. pylori infection. Am J Gastroenterol, 92, 1853-7.
  10. Hussain SP, Hofseth LJ, Harris CC (2003). Radical causes of cancer. Nat Rev Cancer, 3, 276-85. https://doi.org/10.1038/nrc1046
  11. Jang TJ, Kim JR (2000). Proliferation and apoptosis in gastric antral epithelial cells of patients infected with Helicobacter pylori. J Gastroenterol, 35, 265-71. https://doi.org/10.1007/s005350050344
  12. Kasai H (1997). Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res, 387, 147-63. https://doi.org/10.1016/S1383-5742(97)00035-5
  13. Katsurahara M, Kobayashi Y, Iwasa M, et al (2009). Reactive nitrogen species mediate DNA damage in Helicobacter pylori-infected gastric mucosa. Helicobacter, 14, 552-8. https://doi.org/10.1111/j.1523-5378.2009.00719.x
  14. Kehrer JP (1993). Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol, 23, 21-48. https://doi.org/10.3109/10408449309104073
  15. Khodaii Z, Ghaderian SM, Akbarzadeh Najar R, et al (2011). cagA and vacA status and influence of Helicobacter pylori infection on serum oxidative DNA damage in Iranian patients with peptic ulcer disease. Ir J Med Sci, 180, 155-61. https://doi.org/10.1007/s11845-010-0548-5
  16. Ladeira MS, Rodrigues MA, Salvadori DM, et al (2004). DNA damage in patients infected by Helicobacter pylori. Cancer Epidemiol Biomarkers Prev, 13, 631-7.
  17. Lunec J, Holloway KA, Cooke MS, et al (2002). Urinary 8-oxo-2'-deoxyguanosine: redox regulation of DNA repair in vivo? Free Radic Biol Med, 33, 875-85. https://doi.org/10.1016/S0891-5849(02)00882-1
  18. Ma Y, Zhang L, Rong S, et al (2013). Relation between gastric cancer and protein oxidation, DNA damage, and lipid peroxidation. Oxid Med Cell Longev, 2013, 543760.
  19. Margaret AL, Syahruddin E, Wanandi SI (2011). Low activity of manganese superoxide dismutase (MnSOD) in blood of lung cancer patients with smoking history: relationship to oxidative stress. Asian Pac J Cancer Prev, 12, 3049-53.
  20. Moradi MT, Yari K, Rahimi Z, et al (2015). Manganese superoxide dismutase (MnSOD Val-9Ala) gene polymorphism and susceptibility to gastric cancer. Asian Pac J Cancer Prev, 16, 485-8. https://doi.org/10.7314/APJCP.2015.16.2.485
  21. Moss S, Calam J (1992). Helicobacter pylori and peptic ulcers: the present position. Gut, 33, 289-92. https://doi.org/10.1136/gut.33.3.289
  22. Murata M, Thanan R, Ma N, et al (2012). Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis. J Biomed Biotechnol, 2012, 623019.
  23. Naito Y, Yoshikawa T (2002). Molecular and cellular mechanisms involved in Helicobacter pylori-induced inflammation and oxidative stress. Free Radic Biol Med, 33, 323-36. https://doi.org/10.1016/S0891-5849(02)00868-7
  24. Nishibayashi H, Kanayama S, Kiyohara T, et al (2003). Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma. J Gastroenterol Hepatol, 18, 1384-91. https://doi.org/10.1046/j.1440-1746.2003.03192.x
  25. Noorgaard A, Andersen LP, Nielsen H (1995). Neutrophil degranulation by Helicobacter pylori proteins. Gut, 36, 354-7. https://doi.org/10.1136/gut.36.3.354
  26. Ohnishi S, Ma N, Thanan R, et al (2013). DNA damage in inflammation-related carcinogenesis and cancer stem cells. Oxid Med Cell Longev, 2013, 387014.
  27. Peek RM (2002). Helicobacter pylori strain-specific modulation of gastric mucosal cellular turnover: implications for carcinogenesis. J Gastroenterol, 37, 10-6.
  28. Raza Y, Khan A, Farooqui A, et al (2014). Oxidative DNA damage as a potential early biomarker of helicobacter pylori associated carcinogenesis. Pathol Oncol Res, 20, 839-46. https://doi.org/10.1007/s12253-014-9762-1
  29. Witherell HL, Hiatt RA, Replogle M, et al (1998). Helicobacter pylori infection and urinary excretion of 8-hydroxy-2-deoxyguanosine, an oxidative DNA adduct. Cancer Epidemiol Biomarkers Prev, 7, 91-6.

Cited by

  1. eradication vol.52, pp.2, 2018, https://doi.org/10.1080/10715762.2017.1418981
  2. Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial vol.7, pp.13, 2018, https://doi.org/10.1161/JAHA.117.008226