HELICOBACTER PYLORI’NİN NEDEN OLDUĞU EPİGENETİK VE GENETİK DEĞİŞİKLİKLER VE GASTRİK KARSİNOJENEZ GELİŞİMİNDE ROLLERİ

Yıl 2019, Cilt: 43 Sayı: 3, 285 - 308, 08.09.2019

Didem Oral Anıl Yirün , Pınar Erkekoğlu

https://doi.org/10.33483/jfpau.544386

Cited By: 2

Öz

        Amaç: Helicobacter
pylori mide mukozasında kolonize olan bir bakteridir ve dünya genelinde en
yaygın infeksiyon hastalıklarından birisidir. Helicobacter pylori’nin gastrik
kanser ve mukoza-assosiye lenfoid doku (MALT) lenfomaya neden olduğuna dair
bulgular vardır. Bu bakterinin gastrik karsinojenez gelişimindeki etki
mekanizmaları ile ilgili pek çok çalışma yapılmış olup, hem epigenetik hem de
genetik mekanizmaların bu süreçte etkili olduğu belirtilmektedir. Bu derlemede,
Helicobacter pylori’nin neden olduğu gastrik karsinojenez sürecindeki epigenetik
ve genetik mekanizmalar değerlendirilecektir.

       
Gereç ve Yöntem: Helicobacter
pylori’nin neden olduğu epigenetik ve genetik değişiklikler ve gastrik
karsinojenez gelişimindeki rolünün tespiti için yapılan çalışmaların kapsamlı
olarak derlenebilmesi için başta PUBMED olmak üzere sağlık bilimleri alanındaki
veri tabanları kullanılmış ve özellikle de son on yılda bu konuda yayınlanan
makalelerden yararlanılmıştır.

        Sonuç ve Tartışma: Helicobacter
pylori’nin neden olduğu karsinojenezin gelişiminde kronik inflamasyonun yol
açtığı oksidatif stres, bakteriyel virülans faktörleri, konakçıya bağlı
intrinsik ve ekstrinsik faktörlerin bir bütün olarak tetiklediği epigenetik ve
genetik mekanizmalar rol oynamaktadır. Ancak, bu Helicobacter pylori’nin yol
açtığı tüm epigenetik ve genetik değişiklikler henüz tam olarak anlaşılmamış
olup, daha fazla in vivo ve in vitro mekanistik çalışmaya gereksinim
duyulmaktadır. 

Anahtar Kelimeler

Helicobacter pylori, epigenetik mekanizmalar, DNA hasarı, gastrik karsinojenez

EPIGENETIC AND GENETIC CHANGES CAUSED BY HELICOBACTER PYLORI AND THEIR ROLES IN GASTRIC CARCINOGENESIS

Öz

        Objective: Helicobacter
pylori is a bacteria which colonizes in the gastric mucosa and it is one of the
major infectious diseases throughout the world. There are findings pointing out
that Helicobacter pylori can cause gastric cancer and mucosa-associated
lymphoid tissue (MALT) lymphoma. There are several studies on the mechanism of
action of this bacterium and it is indicated that both epigenetic and genetic
mechanisms are effective in this process. In this review, we will evaluate
epigenetic and genetic mechanisms caused by Helicobacter pylori through gastric
carcinogenesis development.

        Material and Method: In order to review the epigenetic and
genetic mechanisms caused by Helicobacter pylori and their roles in gastric
carcinogenesis development comprehensively, the health sciences databases
including PUBMED were used and particularly the scientific papers on thse
sbject published in the last ten years were used.

        Result and Discussion: The epigenetic and genetic mechanisms caused by chronic
inflammation (like oxidative stress, bacterial virulance factors, intrinsic and
extrinsic fators) may trigger the gastric carcinogenesis development by
Helicobacter pylori as a whole. However, all of the epigenetic and genetic
alterations caused by Helicobacter pylori are not yet fully understood and more
in vivo ve in vitro mechanistic studies are needed.

Anahtar Kelimeler

epigenetic mechanisms, DNA damage, gastric carcinogenesis, Helicobacter pylori, Helicobacter pylori

Kaynakça

• 1. Nardone, G., Compare, D., De Colibus, P., de Nucci, G., Rocco, A. (2007). Helicobacter pylori and epigenetic mechanisms underlying gastric carcinogenesis. Digestive Diseases, 25(3), 225-229.
• 2. Nakajima, T., Maekita, T., Oda, I., Gotoda, T., Yamamoto, S., Umemura, S., Ichinose, M., Sugimura, T., Ushijima, T., Saito, D. (2006). Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Cancer, Epidemiology Biomarkers & Prevention, 15(11), 2317-2321.
• 3. Chiba, T., Marusawa, H., Ushijima, T. (2012). Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation. Gastroenterology, 143(3), 550-563.
• 4. Kawanishi, S., Hiraku, Y., Pinlaor, S., Ma, N. (2006). Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis. Biological Chemistry, 387(4), 365-372.
• 5. Mager, D.L. (2006). Bacteria and cancer: cause, coincidence or cure? A review. Journal of Translational Medicine, 28, 4, 14.
• 6. Weitzman, M.D., Weitzman, J.B. (2014). What's the damage? The impact of pathogens on pathways that maintain host genome integrity. Cell Host & Microbe, 15(3), 283-294.
• 7. Correa, P. (2003). Helicobacter pylori infection and gastric cancer. Cancer, Epidemiology, Biomarkers & Prevention, 12(3), 238s-241s.
• 8. Nishizawa, T., Suzuki, H. (2015). Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy. Biomedical Research International, 2015, 794378.
• 9. Ladeira, M.S., Bueno, R.C., Dos Santos, B.F., Pinto, C.L., Prado, R.P., Silveira, M.G., Rodrigues, M.A., Bartchewsky, W. Jr., Pedrazzoli, J. Jr., Ribeiro, M.L., Salvadori, D.M. (2008). Relationship among oxidative DNA damage, gastric mucosal density and therelevance of cagA, vacA and iceA genotypes of Helicobacter pylori. Digestive Diseases and Sciences, 53(1), 248-255.
• 10. Toller, I.M., Neelsen, K.J., Steger, M., Hartung, M.L., Hottiger, M.O., Stucki, M., Kalali, B., Gerhard, M., Sartori, A.A., Lopes, M., Müller, A. ( 2011). Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proceedings of National Academy of Sciences U S A. 108(36), 14944-14949.
• 11. Neelapu, N.R.R., Nammi, D., Pasupuleti, A.C.M., Surekka, C. (2014). Helicobacter pylori induced gastric inflamation, ulcer, and cancer: a pathogenesis perspective. International Journal of Inflammation, Cancer and Integrative Therapy, 1, 1000113.
• 12. Blaser, M.J. (1990). Helicobacter pylori and the pathogenesis of gastroduodenal inflammation. Journal of Infectious Diseases, 161(4), 626-633.
• 13. Kusters, J.G., van Vliet, A.H., Kuipers, E.J. (2006). Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews, 19(3), 449-490.
• 14. Burkitt, M.D., Duckworth, C.A., Williams, J.M., Pritchard, D.M. (2017). Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models. Disease Models & Mechanisms, 10(2), 89-104.
• 15. Junaid, M., Linn, A.K., Javadi, M.B., Al-Gubare, S., Ali, N., Katzenmeier, G. (2016). Vacuolating cytotoxin A (VacA) - A multi-talented pore-forming toxin from Helicobacter pylori. Toxicon, 118:27-35.
• 16. Zhang, X.Y., Zhang, P.Y., Aboul-Soud, MA. (2017). From inflammation to gastric cancer: Role of Helicobacter pylori. Oncology Letters, 13(2), 543-548.
• 17. Moss, S.F. (2016). The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer. Cellular and Molecular Gastroenterology and Hepatology, 3(2), 183-191.
• 18. Blaser, M.J. (1992). Helicobacter pylori: its role in disease. Clinical Infectious Diseases, 15(3), 386-391.
• 19. Arabski, M., Klupinska, G., Chojnacki, J., Kazmierczak, P., Wisniewska-Jarosinska, M, Drzewoski, J., Blasiak, J. (2005). DNA damage and repair in Helicobacter pylori-infected gastric mucosa cells. Mutation Research, 570(1), 129-135.
• 20. Valenzuela, M.A., Canales, J., Corvalán, A.H., Quest, A.F. (2015).Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World Journal of Gastroenterology, 21(45), 12742-12756.
• 21. Farinati, F., Cardin, R., Degan, P., Rugge, M., Mario, F.D., Bonvicini, P., Naccarato, R. (1998). Oxidative DNA damage accumulation in gastric carcinogenesis. Gut, 42(3), 351-356.
• 22. Crabtree, J.E., Farmery, S.M., Lindley, I.J., Figura, N., Peichl, P., Tompkins, D.S. (1994). CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. Journal of Clinical Pathology, 47(10), 945-950.
• 23. Kim, J.J., Tao, H., Carloni, E., Leung, W.K., Graham, D.Y., Sepulveda, A.R. (2002). Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology, 123(2), 542-553.
• 24. Zarrilli, R., Ricci, V., Romano, M. (1999).Molecular response of gastric epithelial cells to Helicobacter pylori-induced cell damage. Cellular Microbiology, 1(2), 93-99.
• 25. Xie, Y., Zhou, J.J., Zhao, Y., Zhang, T., Mei, L.Z. (2017). H.pylori modifies methylation of global genomic DNA and the gastrin gene promoter in gastric mucosal cells and gastric cancer cells. Microbiology and Pathology, 108, 129-136.
• 26. Huang, H., Tian, J., Xu, X., Liang, Q., Huang, X., Lu, J., Yao, Y. (2018). A study on the roles of Helicobacter pylori in bile reflux gastritis and gastric cancer. Jornal of BUON, 23(3), 659-664.
• 27. Ushijima, T., Nakajima, T., Maekita, T. (2006). DNA methylation as a marker for the past and future. Journal of Gastroenterology, 41(5), 401-407.
• 28. Chan, A.O., Lam, S.K., Wong, B.C., Wong, W.M., Yuen, M.F., Yeung, Y.H., Hui, W.M., Rashid, A., Kwong, Y.L. (2003). Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut, 52(4), 502-506.
• 29. Chan, A.O., Wong, B.C., Lan, H.Y., Loke, S.L., Chan, W.K., Hui, W.M., Yuen, Y.H., Ng, I., Hou, L., Wong, W.M., Yuen, M.F., Luk, J.M., Lam, SK. (2003). Deregulation of E-cadherin-catenin complex in precancerous lesions of gastric adenocarcinoma. J Gastroenterology and Hepatology, 18(5), 534-539.
• 30. Maeda, M., Moro, H., Ushijima, T. (2017). Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway. Gastric Cancer, 20 (Suppl 1), 8-15.
• 31. Maekita, T., Nakazawa, K., Mihara, M., Nakajima, T., Yanaoka, K., Iguchi, M., Arii, K., Kaneda, A., Tsukamoto, T., Tatematsu, M., Tamura, G., Saito, D., Sugimura, T., Ichinose, M., Ushijima, T. (2006). High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clinical Cancer Research, 12, 989-995.
• 32. Huang, K.K., Ramnarayanan, K., Zhu, F., Srivastava, S., Xu, C., Tan, A.L.K., Lee, M., Tay, S., Das, K., Xing, M., Fatehullah, A., Alkaff, S.M.F., Lim, T.K.H., Lee, J., Ho, K.Y., Rozen, S.G., Teh, B.T., Barker, N., Chia, C.K., Khor, C., Ooi, C.J., Fock, K.M., So, J., Lim, W.C., Ling, K.L., Ang, T.L., Wong, A., Rao, J., Rajnakova, A., Lim, L.G., Yap, W.M., Teh, M., Yeoh, K.G., Tan, P. (2018). Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer. Cancer Cell. 33(1), 137-150.
• 33. Yao, Y., Tao, H., Park, D.I., Sepulveda, J.L., Sepulveda, A.R. (2006). Demonstration and characterization of mutations induced by Helicobacter pylori organisms in gastric epithelial cells. Helicobacter, 11(4), 272-286.
• 34. Niwa, T., Tsukamoto, T., Toyoda, T., Mori, A., Tanaka, H., Maekita, T., Ichinose, M., Tatematsu, M., Ushijima, T. (2010). Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Research, 70(4), 1430-1440.
• 35. Zhang, Y., Liu, H., Zhou, K. (2001). Lack of correlation of vacA genotype, cagA gene of Helicobacter pylori and their expression products with various gastroduodenal diseases. China Medical Journal, 114(7), 703-706.
• 36. Xia, G., Schneider-Stock, R., Diestel, A., Habold, C., Krueger, S., Roessner, A., Naumann, M., Lendeckel, U. (2008). Helicobacter pylori regulates p21(WAF1) by histone H4 acetylation. Biochemical and Biophysical Research Communications, 369(2), 526-531.
• 37. Fehri, L.F., Rechner, C., Janssen, S., Mak, T.N., Holland, C., Bartfeld, S., Brüggemann, H., Meyer, T.F. (2009). Helicobacter pylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation. Epigenetics, 4(8), 577-586.
• 38. Ding, S.Z., Goldberg, J.B., Hatakeyama, M. (2010). Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Future Oncology, 6(5):851-862.
• 39. Santos, J.C., Gambeloni, R.Z., Roque, A.T., Oeck, S., Ribeiro, ML. (2018). Epigenetic Mechanisms of ATM Activation after Helicobacter pylori Infection. American Journal of Pathology, 188(2), 329-335.
• 40. Jang, S.H., Lim, J.W., Morio, T, Kim H. (2012). Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells. Free Radical Biology and Medicine, 52(3), 607-615.
• 41. Hanada, K., Graham, D.Y. (2014).Helicobacter pylori and the molecular pathogenesis of intestinal-type gastric carcinoma. Expert Review of Anticancer Therapy,14(8), 947-954.
• 42. Hanada, K., Uchida, T., Tsukamoto, Y., Watada, M., Yamaguchi, N., Yamamoto, K., Shiota, S., Moriyama, M., Graham, D.Y., Yamaoka, Y. (2014). Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infection and Immunity, 82(10), 4182-4189.
• 43. Xie, C., Xu, L.Y., Yang, Z., Cao, X.M., Li, W., Lu, N.H. (2014).Expression of γH2AX in various gastric pathologies and its association with Helicobacter pylori infection. Oncology Letters, 7(1), 159-163.
• 44. Koeppel, M., Garcia-Alcalde, F., Glowinski, F., Schlaermann, P., Meyer, T.F. (2015). Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells. Cellular Reproduction, 11(11), 1703-1713.
• 45. Machado, A.M., Figueiredo, C., Touati, E., Máximo, V., Sousa, S, Michel, V., Carneiro, F., Nielsen, F.C., Seruca, R., Rasmussen, L.J. (2009). Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells. Clinical Cancer Research, 15(9), 2995-3002.
• 46. Machado, A.M., Desler, C., Bøggild, S., Strickertsson, J.A., Friis-Hansen, L., Figueiredo, C., Seruca, R., Rasmussen, LJ. (2013). Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells. Mechanisms of Ageing and Development, 134(10), 460-6.
• 47. Ding, S.Z., Fischer, W., Kaparakis-Liaskos, M., Liechti, G., Merrell, D.S., Grant, P.A., Ferrero, R.L., Crowe, S.E., Haas, R., Hatakeyama, M., Goldberg, J.B. (2010). Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS One, 5(4), e9875.
• 48. Futagami, S., Hiratsuka, T., Shindo, T., Horie, A., Hamamoto, T., Suzuki, K., Kusunoki, M., Miyake, K., Gudis, K., Crowe, S.E., Tsukui, T., Sakamoto, C. (2008). Expression of apurinic/apyrimidinic endonuclease-1 (APE-1) in H. pylori-associated gastritis,gastric adenoma, and gastric cancer. Helicobacter,13(3), 209-218.
• 49. Leung, W.K., Kim, J.J., Kim, J.G., Graham, D.Y., Sepulveda, A.R. (2000). Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. American Journal of Pathology, 156(2), 537-543.
• 50. Park, D.I., Park, S.H., Kim, S.H., Kim, J.W., Cho, Y.K., Kim, H.J., Sohn, C.I., Jeon, W.K., Kim, B.I., Cho, E.Y., Kim, E.J., Chae, S.W., Sohn, J.H., Sung, I.K., Sepulveda, A.R., Kim, J.J. (2005). Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein. Helicobacter, 10(3), 179-184.
• 51. Hiyama, T., Haruma, K., Kitadai, Y., Masuda, H., Miyamoto, M., Tanaka, S., Yoshihara, M., Shimamoto, F., Chayama, K. (2002). K-ras mutation in Helicobacter pylori-associated chronic gastritis in patients with and without gastric cancer. International Journal of Cancer, 97(5), 562-566.
• 52. Sawa, T., Ohshima, H. (2006). Nitrative DNA damage in inflammation and its possible role in carcinogenesis. Nitric Oxide, 14(2), 91-100.
• 53. Shibata, A., Parsonnet, J., Longacre, T.A., Garcia, M.I., Puligandla, B., Davis, R.E., Vogelman, J.H., Orentreich, N., Habel, L.A. (2002). CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma. Carcinogenesis, 23(3), 419-424.
• 54. Touati, E. (2010). When bacteria become mutagenic and carcinogenic: lessons from H.pylori. Mutation Research, 703(1), 66-70.
• 55. Morgan, C., Jenkins, G.J., Ashton, T., Griffiths, A.P., Baxter, J.N., Parry, E.M., Parry, J.M. (2003). Detection of p53 mutations in precancerous gastric tissue. British Journal of Cancer, 89(7), 1314-1319.