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Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis

  • Olga SokolovaEmail author
  • Michael Naumann
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 421)

Abstract

Over the last years, intensive investigations in molecular biology and cell physiology extended tremendously the knowledge about the association of inflammation and cancer. In frame of this paradigm, the human pathogen Helicobacter pylori triggers gastritis and gastric ulcer disease, and contributes to the development of gastric cancer. Mechanisms, by which the bacteria-induced inflammation in gastric mucosa leads to intestinal metaplasia and carcinoma, are represented in this review. An altered cell-signaling response and increased production of free radicals by epithelial and immune cells account for the accumulation of DNA damage in gastric mucosa, if infection stays untreated. Host genetics and environmental factors, especially diet, can accelerate the process, which offers the opportunity of intervention based on a balanced nutrition. It is supposed that inflammation might influence stem- or progenitor cells in gastric tissue predisposing for metaplasia or tumor relapse. Herein, DNA is strongly mutated and labile, which restricts therapy options. Thus, the understanding of the mechanisms that underlie gastric carcinogenesis will be of preeminent importance for the development of strategies for screening and early detection. As most gastric cancer patients face late-stage disease with a poor overall survival, the development of multi-targeted therapeutic intervention strategies is a major challenge for the future.

Keywords

Helicobacter pylori Oxidative stress DNA repair Genomic instability Stem cells 

Notes

Acknowledgements

This work was supported by the German Research Foundation to M.N. (CRC-854 A04).

References

  1. Aggarwal BB, Sethi G, Nair A, Ichikawa H (2006) Nuclear factor-κB: a Holy Grail in cancer prevention and therapy. Curr Signal Transduct Ther 1(1):25–52.  https://doi.org/10.2174/157436206775269235CrossRefGoogle Scholar
  2. Alexandrov LB, Nik-Zainal S, Siu HC, Leung SY, Stratton MR (2015) A mutational signature in gastric cancer suggests therapeutic strategies. Nat Commun 6:8683.  https://doi.org/10.1038/ncomms9683CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alvarez MC, Santos JC, Maniezzo N, Ladeira MS, da Silva AL, Scaletsky IC, Pedrazzoli J Jr, Ribeiro ML (2013) MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults. World J Gastroenterol 19(20):3043–3051.  https://doi.org/10.3748/wjg.v19.i20.3043CrossRefPubMedPubMedCentralGoogle Scholar
  4. Argent RH, Thomas RJ, Letley DP, Rittig MG, Hardie KR, Atherton JC (2008) Functional association between the Helicobacter pylori virulence factors VacA and CagA. J Med Microbiol 57(Pt 2):145–150.  https://doi.org/10.1099/jmm.0.47465-0CrossRefPubMedGoogle Scholar
  5. Arimoto-Kobayashi S, Ohta K, Yuhara Y, Ayabe Y, Negishi T, Okamoto K, Nakajima Y, Ishikawa T, Oguma K, Otsuka T (2015) Mutagenicity and clastogenicity of extracts of Helicobacter pylori detected by the Ames test and in the micronucleus test using human lymphoblastoid cells. Mutagenesis 30(4):537–544.  https://doi.org/10.1093/mutage/gev016CrossRefPubMedGoogle Scholar
  6. Backert S, Naumann M (2010) What a disorder: Proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol 18:479–486.  https://doi.org/10.1016/j.tim.2010.08.003CrossRefPubMedGoogle Scholar
  7. Backert S, Feller SM, Wessler S (2008) Emerging roles of Abl family tyrosine kinases in microbial pathogenesis. Trends Biochem Sci. 33(2):80–90.  https://doi.org/10.1016/j.tibs.2007.10.006CrossRefPubMedGoogle Scholar
  8. Backert S, Haas R, Gerhard M, Naumann M (2017) The Helicobacter pylori type IV secretion system encoded by the cag Pathogenicity island: architecture, function, and signaling. Curr Top Microbiol Immunol 413:187–220.  https://doi.org/10.1007/978-3-319-75241-9_8CrossRefPubMedGoogle Scholar
  9. Bae M, Lim JW, Kim H (2013) Oxidative DNA damage response in Helicobacter pylori-infected mongolian gerbils. J Cancer Prev 18(3):271–275. https://doi.org/10.15430/JCP.2013.18.3.271
  10. Bernal C, Vargas M, Ossandón F, Santibáñez E, Urrutia J, Luengo V, Zavala LF, Backhouse C, Palma M, Argandoña J, Aguayo F, Corvalán A (2008) DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis. Biol Res 41(3):303–315.  https://doi.org/10.4067/S0716-97602008000300007CrossRefPubMedGoogle Scholar
  11. Brisslert M, Enarsson K, Lundin S, Karlsson A, Kusters JG, Svennerholm AM, Backert S, Quiding-Järbrink M (2005) Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP. FEMS Microbiol Lett 249(1):95–103CrossRefGoogle Scholar
  12. Bulbuloglu E, Inanc F, Bakaris S, Kantarceken B, Cetinkaya A, Cağlar R, Ilhami TK, Kilinc M (2005) Association of adenosine deaminase, superoxide dismutase, and catalase activities with Helicobacter pylori. Dig Dis Sci 50(12):2296–2299.  https://doi.org/10.1007/s10620-005-3050-6CrossRefPubMedGoogle Scholar
  13. Butcher LD, den Hartog G, Ernst PB, Crowe SE (2017) Oxidative stress resulting from Helicobacter pylori infection contributes to gastric cancerogenesis. Cell Mol Gastroenterol Hepathol 3:316–322CrossRefGoogle Scholar
  14. Calvino-Fernández M, Benito-Martínez S, Parra-Cid T (2008) Oxidative stress by Helicobacter pylori causes apoptosis through mitochondrial pathway in gastric epithelial cells. Apoptosis 13(10):1267–1280.  https://doi.org/10.1007/s10495-008-0255-0CrossRefPubMedGoogle Scholar
  15. Cancer Genome Atlas Research Network. Collaborators (315) (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517):202–209.  https://doi.org/10.1038/nature13480CrossRefGoogle Scholar
  16. Cavallo P, Cianciulli A, Mitolo V, Panaro MA (2011) Lipopolysaccharide (LPS) of helicobacter modulates cellular DNA repair systems in intestinal cells. Clin Exp Med 11(3):171–179.  https://doi.org/10.1007/s10238-010-0118-1CrossRefPubMedGoogle Scholar
  17. Chaturvedi R, Asim M, Romero-Gallo J, Barry DP, Hoge S, de Sablet T, Delgado AG, Wroblewski LE, Piazuelo MB, Yan F, Israel DA, Casero RA Jr, Correa P, Gobert AP, Polk DB, Peek RM Jr, Wilson KT (2011) Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA. Gastroenterology 141(5):1696–1708.  https://doi.org/10.1053/j.gastro.2011.07.045CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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.  https://doi.org/10.1053/j.gastro.2012.07.009CrossRefPubMedGoogle Scholar
  19. Choi YJ, Kim N, Chang H, Lee HS, Park SM, Park JH, Shin CM, Kim JM, Kim JS, Lee DH, Jung HC (2015) Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells. Carcinogenesis 36(5):553–563.  https://doi.org/10.1053/j.gastro.2012.07.009CrossRefPubMedGoogle Scholar
  20. Cover TL, Blaser MJ (2009) Helicobacter pylori in health and disease. Gastroenterology 136(6):1863–1873.  https://doi.org/10.1053/j.gastro.2009.01.073CrossRefPubMedPubMedCentralGoogle Scholar
  21. Davalli P, Marverti G, Lauriola A, D’Arca D (2018) Targeting oxidatively induced DNA damage response in cancer: opportunities for novel cancer therapies. Oxid Med Cell Longev 2018:2389523.  https://doi.org/10.1155/2018/2389523CrossRefPubMedPubMedCentralGoogle Scholar
  22. Davies GR, Simmonds NJ, Stevens TR, Sheaff MT, Banatvala N, Laurenson IF, Blake DR, Rampton DS (1994) Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut 35:179–185.  https://doi.org/10.1136/gut.35.2.179CrossRefPubMedPubMedCentralGoogle Scholar
  23. De Luca P, De Siervi A (2016) Critical role for BRCA1 expression as a marker of chemosensitivity response and prognosis. Front Biosci (Elite Ed) 8:72–83.  https://doi.org/10.2741/752CrossRefGoogle Scholar
  24. den Hartog G, Chattopadhyay R, Ablack A, Hall EH, Butcher LD, Bhattacharyya A, Eckmann L, Harris PR, Das S, Ernst PB, Crowe SE (2016) Regulation of Rac1 and reactive oxygen species production in response to infection of gastrointestinal epithelia. PLoS Pathog 12(1):e1005382.  https://doi.org/10.1371/journal.ppat.1005382CrossRefGoogle Scholar
  25. Deng N, Liu JW, Sun LP, Xu Q, Duan ZP, Dong NN, Yuan Y (2014) Expression of XPG protein in the development, progression and prognosis of gastric cancer. PLoS ONE 9(9):e108704.  https://doi.org/10.1371/journal.pone.0108704CrossRefPubMedPubMedCentralGoogle Scholar
  26. Ding SZ, O’Hara AM, Denning TL, Dirden-Kramer B, Mifflin RC, Reyes VE, Ryan KA, Elliott SN, Izumi T, Boldogh I, Mitra S, Ernst PB, Crowe SE (2004) Helicobacter pylori and H2O2 increase AP endonuclease-1/redox factor-1 expression in human gastric epithelial cells. Gastroenterology 127(3):845–858.  https://doi.org/10.1053/j.gastro.2004.06.017CrossRefPubMedGoogle Scholar
  27. Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE (2007) Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect Immun 75:4030–4039.  https://doi.org/10.1128/IAI.00172-07CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ding SZ, Goldberg JB, Hatakeyama M (2010a) Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Future Oncol 6(5):851–862.  https://doi.org/10.2217/fon.10.37CrossRefPubMedPubMedCentralGoogle Scholar
  29. Ding SZ, Fischer W, Kaparakis-Liaskos M, Liechti G, Merrell DS, Grant PA, Ferrero RL, Crowe SE, Haas R, Hatakeyama M, Goldberg JB (2010b) Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS ONE 5(4):e9875.  https://doi.org/10.1371/journal.pone.0009875CrossRefPubMedPubMedCentralGoogle Scholar
  30. Ding Y, Yang Q, Wang B, Ye G, Tong X (2016) The correlation of MGMT promoter methylation and clinicopathological features in gastric cancer: a systematic review and meta-analysis. PLoS ONE 11(11):e0165509.  https://doi.org/10.1371/journal.pone.0165509CrossRefPubMedPubMedCentralGoogle Scholar
  31. Donnelly JM, Engevik AC, Engevik M, Schumacher MA, Xiao C, Yang L, Worrell RT, Zavros Y (2014) Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell. Dig Dis Sci 59(3):569–582.  https://doi.org/10.1007/s10620-013-2927-zCrossRefPubMedGoogle Scholar
  32. Dulger AC, Aslan M, Nazligul Y, Horoz M, Bolukbas C, Bolukbas FF, Celik H, Kocyigit A (2011) Peripheral lymphocyte DNA damage and oxidative status after eradication therapy in patients infected with Helicobacter pylori. Pol Arch Med Wewn 121(12):428–432 PMID: 22012003PubMedGoogle Scholar
  33. Echizen K, Hirose O, Maeda Y, Oshima M (2016) Inflammation in gastric cancer: Interplay of the COX-2/prostaglandin E2 and Toll-like receptor/MyD88 pathways. Cancer Sci 107(4):391–397.  https://doi.org/10.1111/cas.12901CrossRefPubMedPubMedCentralGoogle Scholar
  34. Elingarami S, Liu H, Kalinjuma AV, Hu W, Li S, He N (2015) Polymorphisms in NEIL-2, APE-1, CYP2E1 and MDM2 genes are independent predictors of gastric cancer risk in a Northern Jiangsu Population (China). J Nanosci Nanotechnol 15(7):4815–4828.  https://doi.org/10.1166/jnn.2015.10028CrossRefPubMedGoogle Scholar
  35. Elseweidy MM, Taha MM, Younis NN, Ibrahim KS, Hamouda HA, Eldosouky MA, Soliman H (2010) Gastritis induced by Helicobacter pylori infection in experimental rats. Dig Dis Sci 55(10):2770–2777.  https://doi.org/10.1007/s10620-009-1103-yCrossRefPubMedGoogle Scholar
  36. Farinati F, Cardin R, Bortolami M, Nitti D, Basso D, de Bernard M, Cassaro M, Sergio A, Rugge M (2008) Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism. Int J Cancer 123(1):51–55.  https://doi.org/10.1159/000320052CrossRefPubMedGoogle Scholar
  37. Fu HW (2014) Helicobacter pylori neutrophil-activating protein: from molecular pathogenesis to clinical applications. World J Gastroenterol 20(18):5294–5301.  https://doi.org/10.3748/wjg.v20.i18.5294CrossRefPubMedPubMedCentralGoogle Scholar
  38. Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SJ, Wilson KT (1999) Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 116(6):1319–1329.  https://doi.org/10.1016/S0016-5085(99)70496-8CrossRefPubMedGoogle Scholar
  39. Fu HW (2014) Helicobacter pylori neutrophil-activating protein: from molecular pathogenesis to clinical applications. World J Gastroenterol 20(18):5294–5301.  https://doi.org/10.3748/wjg.v20.i18.5294.
  40. Fu H, Ma Y, Yang M, Zhang C, Huang H, Xia Y, Lu L, Jin W, Cui D (2016) Persisting and increasing neutrophil infiltration associates with gastric carcinogenesis and E-cadherin downregulation. Sci Rep 6:29762.  https://doi.org/10.1038/srep29762CrossRefPubMedPubMedCentralGoogle Scholar
  41. Fujii Y, Yoshihashi K, Suzuki H, Tsutsumi S, Mutoh H, Maeda S, Yamagata Y, Seto Y, Aburatani H, Hatakeyama M (2012) CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5. Proc Natl Acad Sci USA 109(50):20584–20589.  https://doi.org/10.1073/pnas.1208651109CrossRefPubMedGoogle Scholar
  42. Futagami S, Hiratsuka T, Shindo T, Horie A, Hamamoto T, Suzuki K, Kusunoki M, Miyake K, Gudis K, Crowe SE, Tsukui T, Sakamoto C (2008) Expression of apurinic/apyrimidinic endonuclease-1 (APE-1) in Helicobacter pylori-associated gastritis, gastric adenoma, and gastric cancer. Helicobacter 13(3):209–218.  https://doi.org/10.1111/j.1523-5378.2008.00605.xCrossRefPubMedGoogle Scholar
  43. Gao JP, Xu W, Liu WT, Yan M, Zhu ZG (2018) Tumor heterogeneity of gastric cancer: from the perspective of tumor-initiating cell. World J Gastroenterol 24(24):2567–2581.  https://doi.org/10.3748/wjg.v24.i24.2567CrossRefPubMedPubMedCentralGoogle Scholar
  44. Giannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI (2008) Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci USA 105(11):4358–4363.  https://doi.org/10.1073/pnas.0800668105CrossRefPubMedGoogle Scholar
  45. Gobert AP, Wilson KT (2017) Polyamine- and NADPH-dependent generation of ROS during Helicobacter pylori infection: A blessing in disguise. Free Radic Biol Med 105:16–27.  https://doi.org/10.1016/j.freeradbiomed.2016.09.024CrossRefPubMedGoogle Scholar
  46. Goldenring JR, Nam KT, Mills JC (2011) The origin of pre-neoplastic metaplasia in the stomach: chief cells emerge from the Mist. Exp Cell Res 317(19):2759–2764.  https://doi.org/10.1016/j.yexcr.2011.08.017CrossRefPubMedPubMedCentralGoogle Scholar
  47. Gong M, Ling SS, Lui SY, Yeoh KG, Ho B (2010) Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology 139(2):564–573.  https://doi.org/10.1053/j.gastro.2010.03.050CrossRefPubMedGoogle Scholar
  48. Goto A, Hirahashi M, Osada M, Nakamura K, Yao T, Tsuneyoshi M, Takayanagi R, Oda Y (2011) Aberrant activation-induced cytidine deaminase expression is associated with mucosal intestinalization in the early stage of gastric cancer. Virchows Arch 458(6):717–724.  https://doi.org/10.1007/s00428-011-1086-xCrossRefPubMedGoogle Scholar
  49. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G et al (2007) Patterns of somatic mutation in human cancer genomes. Nature 446(7132):153–158.  https://doi.org/10.1038/nature05610CrossRefPubMedPubMedCentralGoogle Scholar
  50. Guo Y, Nie Q, MacLean AL, Li Y, Lei J, Li S (2017) Multiscale modeling of inflammation-induced tumorigenesis reveals competing oncogenic and oncoprotective roles for inflammation. Cancer Res 77(22):6429–6441.  https://doi.org/10.1158/0008-5472.CAN-17-1662CrossRefPubMedGoogle Scholar
  51. Hanada K, Uchida T, Tsukamoto Y, Watada M, Yamaguchi N, Yamamoto K, Shiota S, Moriyama M, Graham DY, Yamaoka Y (2014) Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infect Immun 82(10):4182–4189.  https://doi.org/10.1128/IAI.02368-14CrossRefPubMedPubMedCentralGoogle Scholar
  52. Handa O, Naito Y, Yoshikawa T (2011) Redox biology and gastric carcinogenesis: the role of Helicobacter pylori. Redox Rep 16(1):1–7.  https://doi.org/10.1179/174329211X12968219310756CrossRefPubMedGoogle Scholar
  53. Hartung ML, Gruber DC, Koch KN, Grüter L, Rehrauer H, Tegtmeyer N, Backert S, Müller A (2015) Helicobacter pylori-Induced DNA strand breaks are introduced by nucleotide excision repair endonucleases and promote NF-κB target gene expression. Cell Rep 13(1):70–79.  https://doi.org/10.1016/j.celrep.2015.08.074CrossRefPubMedGoogle Scholar
  54. Hatakeyama M (2014) Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell Host Microbe 15(3):306–316.  https://doi.org/10.1016/j.chom.2014.02.008CrossRefPubMedGoogle Scholar
  55. Hauer MH, Gasser SM (2017) Chromatin and nucleosome dynamics in DNA damage and repair. Genes Dev 31(22):2204–2221.  https://doi.org/10.1101/gad.307702.117CrossRefPubMedPubMedCentralGoogle Scholar
  56. Hayakawa Y, Ariyama H, Stancikova J, Sakitani K, Asfaha S, Renz BW, Dubeykovskaya ZA, Shibata W, Wang H, Westphalen CB, Chen X, Takemoto Y, Kim W, Khurana SS, Tailor Y, Nagar K, Tomita H, Hara A, Sepulveda AR, Setlik W, Gershon MD, Saha S, Ding L, Shen Z, Fox JG, Friedman RA, Konieczny SF, Worthley DL, Korinek V, Wang TC (2015) Mist1 expressing gastric stem cells maintain the normal and neoplastic gastric epithelium and are supported by a perivascular stem cell niche. Cancer Cell 28(6):800–814.  https://doi.org/10.1016/j.ccell.2015.10.003CrossRefPubMedPubMedCentralGoogle Scholar
  57. Hoffmann W (2015) Current status on stem cells and cancers of the gastric epithelium. Int J Mol Sci 16(8):19153–19169.  https://doi.org/10.3390/ijms160819153CrossRefPubMedPubMedCentralGoogle Scholar
  58. Holbrook JD, Parker JS, Gallagher KT, Halsey WS, Hughes AM, Weigman VJ, Lebowitz PF, Kumar R (2011) Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine. J Transl Med 9:119.  https://doi.org/10.1186/1479-5876-9-119CrossRefPubMedPubMedCentralGoogle Scholar
  59. Houghton J, Wang TC (2005) Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 128(6):1567–1578.  https://doi.org/10.1053/j.gastro.2005.03.037CrossRefPubMedGoogle Scholar
  60. Huang XW, Luo RH, Zhao Q, Shen ZZ, Huang LL, An XY, Zhao LJ, Wang J, Huang YZ (2011) Helicobacter pylori induces mitochondrial DNA mutation and reactive oxygen species level in AGS cells. Int J Med Sci 8(1):56–67.  https://doi.org/10.7150/ijms.8.56CrossRefPubMedPubMedCentralGoogle Scholar
  61. Huang KK, Ramnarayanan K, Zhu F, Srivastava S, Xu C, Tan ALK, Lee M, Tay S, Das K, Xing M, Fatehullah A, Alkaff SMF, Lim TKH, Lee J, Ho KY, Rozen SG, Teh BT, Barker N, Chia CK, Khor C, Ooi CJ, Fock KM, So J, Lim WC, Ling KL, Ang TL, Wong A, Rao J, Rajnakova A, Lim LG, Yap WM, Teh M, Yeoh KG, 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.e5.  https://doi.org/10.1016/j.ccell.2017.11.018CrossRefPubMedGoogle Scholar
  62. Hudler P (2012) Genetic aspects of gastric cancer instability. Sci World J 2012:761909.  https://doi.org/10.1100/2012/761909CrossRefGoogle Scholar
  63. Hung WY, Wu CW, Yin PH, Chang CJ, Li AF, Chi CW, Wei YH, Lee HC (2010) Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochim Biophys Acta 1800:264–270.  https://doi.org/10.1016/j.bbagen.2009.06.006CrossRefPubMedGoogle Scholar
  64. Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H, Masuko T, Shimizu T, Ishikawa T, Kai K, Takahashi E, Imamura Y, Baba Y, Ohmura M, Suematsu M, Baba H, Saya H (2011) CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 19(3):387–400.  https://doi.org/10.1016/j.ccr.2011.01.038CrossRefPubMedPubMedCentralGoogle Scholar
  65. Jang SH, Lim JW, Morio T, Kim H (2012) Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells. Free Radic Biol Med 52(3):607–615.  https://doi.org/10.1016/j.freeradbiomed.2011.11.010CrossRefPubMedGoogle Scholar
  66. Jimenez-Del-Rio M, Velez-Pardo C (2012) The bad, the good, and the ugly about oxidative stress. Oxid Med Cell Longev 2012:163913.  https://doi.org/10.1155/2012/163913
  67. Jüttner S, Cramer T, Wessler S, Walduck A, Gao F, Schmitz F, Wunder C, Weber M, Fischer SM, Schmidt WE, Wiedenmann B, Meyer TF, Naumann M, Höcker M (2003) Helicobacter pylori stimulates host cyclooxygenase-2 gene transcription: critical importance of MEK/ERK-dependent activation of USF1/-2 and CREB transcription factors. Cell Microbiol 5(11):821–834.  https://doi.org/10.1046/j.1462-5822.2003.00324.xCrossRefPubMedGoogle Scholar
  68. Kalisperati P, Spanou E, Pateras IS, Korkolopoulou P, Varvarigou A, Karavokyros I, Gorgoulis VG, Vlachoyiannopoulos PG, Sougioultzis S (2017) Inflammation, DNA damage, Helicobacter pylori and gastric tumorigenesis. Front Genet 8:20.  https://doi.org/10.1038/oncsis.2014.42CrossRefPubMedPubMedCentralGoogle Scholar
  69. Karaman A, Kabalar ME, Binici DN, Oztürk C, Pirim I (2010) Genetic alterations in gastric precancerous lesions. Genet Couns 21(4):439–450PubMedGoogle Scholar
  70. Kato K, Hasui K, Wang J, Kawano Y, Aikou T, Murata F (2008) Homeostatic mass control in gastric non-neoplastic epithelia under infection of Helicobacter pylori: an immunohistochemical analysis of cell growth, stem cells and programmed cell death. Acta Histochem Cytochem 41(3):23–38.  https://doi.org/10.1267/ahc.07021CrossRefPubMedPubMedCentralGoogle Scholar
  71. Katsurahara M, Kobayashi Y, Iwasa M, Ma N, Inoue H, Fujita N, Tanaka K, Horiki N, Gabazza EC, Takei Y (2009) Reactive nitrogen species mediate DNA damage in Helicobacter pylori-infected gastric mucosa. Helicobacter 14(6):552–558.  https://doi.org/10.1111/j.1523-5378.2009.00719.xCrossRefPubMedGoogle Scholar
  72. Kidane D, Murphy DL, Sweasy JB (2014) Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection. Oncogenesis 3:e128.  https://doi.org/10.1038/oncsis.2014.42CrossRefPubMedPubMedCentralGoogle Scholar
  73. Kim MJ, Kim H (2015) Anticancer effect of lycopene in gastric carcinogenesis. J Cancer Prev 20(2):92–96.  https://doi.org/10.15430/JCP.2015.20.2.92CrossRefPubMedPubMedCentralGoogle Scholar
  74. Kim YR, Chung NG, Kang MR, Yoo NJ, Lee SH (2010) Novel somatic frameshift mutations of genes related to cell cycle and DNA damage response in gastric and colorectal cancers with microsatellite instability. Tumori 96(6):1004–1009. PMID: 21388066 https://www.ncbi.nlm.nih.gov/pubmed/21388066
  75. Kim MS, An CH, Kim SS, Yoo NJ, Lee SH (2011) Frameshift mutations of poly(adenosine diphosphate-ribose) polymerase genes in gastric and colorectal cancers with microsatellite instability. Hum Pathol 42(9):1289–1296.  https://doi.org/10.1016/j.humpath.2010.11.020CrossRefPubMedGoogle Scholar
  76. Kim YJ, Kim EH, Hahm KB (2012) Oxidative stress in inflammation-based gastrointestinal tract diseases: challenges and opportunities. J Gastroenterol Hepatol 27(6):1004–1010.  https://doi.org/10.1111/j.1440-1746.2012.07108.xCrossRefPubMedGoogle Scholar
  77. Kim HS, Choi SI, Min HL, Kim MA, Kim WH (2013) Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM) gene and ATM protein loss in primary gastric cancer with microsatellite instability. PLoS ONE 8(12):e82769.  https://doi.org/10.1371/journal.pone.0082769CrossRefPubMedPubMedCentralGoogle Scholar
  78. Kiraly O, Gong G, Olipitz W, Muthupalani S, Engelward BP (2015) Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet 11(2):e1004901.  https://doi.org/10.1371/journal.pgen.1004901CrossRefPubMedPubMedCentralGoogle Scholar
  79. Koeppel M, Garcia-Alcalde F, Glowinski F, Schlaermann P, Meyer TF (2015) Helicobacter pylori infection causes characteristic DNA damage patterns in human cells. Cell Rep 11(11):1703–1713.  https://doi.org/10.1016/j.celrep.2015.05.030CrossRefPubMedGoogle Scholar
  80. Langley RE, Rothwell PM (2014) Aspirin in gastrointestinal oncology: new data on an old friend. Curr Opin Oncol 26(4):441–447.  https://doi.org/10.1097/CCO.0000000000000098CrossRefPubMedGoogle Scholar
  81. Larussa T, Leone I, Suraci E, Imeneo M, Luzza F (2015) Helicobacter pylori and T helper cells: mechanisms of immune escape and tolerance. J Immunol Res 2015:981328.  https://doi.org/10.1155/2015/981328CrossRefPubMedPubMedCentralGoogle Scholar
  82. Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49.  https://doi.org/10.1111/apm.1965.64.1.31CrossRefPubMedGoogle Scholar
  83. Lee S, Shin MG, Jo WH, Kim MJ, Kim HR, Lee WS, Park DH, Won JH, Shin JH, Suh SP, Ryang DW (2007) Association between Helicobacter pylori-related peptic ulcer tissue and somatic mitochondrial DNA mutations. Clin Chem 53(7):1390–1392.  https://doi.org/10.1373/clinchem.2007.088047CrossRefPubMedGoogle Scholar
  84. Lee HC, Huang KH, Yeh TS, Chi CW (2014) Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression. World J Gastroenterol 20(14):3950–3959.  https://doi.org/10.3748/wjg.v20.i14.3950CrossRefPubMedPubMedCentralGoogle Scholar
  85. Lee WP, Hou MC, Lan KH, Li CP, Chao Y, Lin HC, Lee SD (2016) Helicobacter pylori-induced chronic inflammation causes telomere shortening of gastric mucosa by promoting PARP-1-mediated non-homologous end joining of DNA. Arch Biochem Biophys 606:90–98.  https://doi.org/10.1016/j.abb.2016.07.014CrossRefPubMedGoogle Scholar
  86. Li Q, Jia Z, Wang L, Kong X, Li Q, Guo K, Tan D, Le X, Wei D, Huang S, Mishra L, Xie K (2012) Disruption of Klf4 in villin-positive gastric progenitor cells promotes formation and progression of tumors of the antrum in mice. Gastroenterology 142(3):531–542.  https://doi.org/10.1053/j.gastro.2011.11.034CrossRefPubMedGoogle Scholar
  87. Ling SS, Yeoh KG, Ho B (2013) Helicobacter pylori γ-glutamyl transpeptidase: a formidable virulence factor. World J Gastroenterol 19(45):8203–8210.  https://doi.org/10.3748/wjg.v19.i45.8203CrossRefPubMedPubMedCentralGoogle Scholar
  88. Liu L, Gerson SL (2006) Targeted modulation of MGMT: clinical implication. Clin Cancer Res 12(2):328–331.  https://doi.org/10.1158/1078-0432.CCR-05-2543CrossRefPubMedGoogle Scholar
  89. Liu X, Meltzer SJ (2017) Gastric cancer in the era of precision medicine. Cell Mol Gastroenterol Hepatol 3(3):348–358.  https://doi.org/10.1016/j.jcmgh.2017.02.003CrossRefPubMedPubMedCentralGoogle Scholar
  90. Machado AM, Figueiredo C, Seruca R, Rasmussen RJ (2010) Helicobacter pylori infection generates genetic instability in gastric cells. Biochim Biophys Acta 1806(1):58–65.  https://doi.org/10.1016/j.bbcan.2010.01.007CrossRefPubMedGoogle Scholar
  91. Machado AM, Desler C, Bøggild S, Strickertsson JA, 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. Mech Ageing Dev 134(10):460–466.  https://doi.org/10.1016/j.mad.2013.08.004CrossRefPubMedGoogle Scholar
  92. 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.  https://doi.org/10.1007/s10120-016-0650-0CrossRefPubMedGoogle Scholar
  93. Maeda M, Yamashita S, Shimazu T, Iida N, Takeshima H, Nakajima T, Oda I, Nanjo S, Kusano C, Mori A, Moro H, Yamada H, Tsugane S, Sugiyama T, Sakai Y, Ushijima T (2018) Novel epigenetic markers for gastric cancer risk stratification in individuals after Helicobacter pylori eradication. Gastric Cancer.  https://doi.org/10.1007/s10120-018-0803-4
  94. Maleki SS, Röcken C (2017) Chromosomal instability in gastric cancer biology. Neoplasia 19(5):412–420.  https://doi.org/10.1016/j.neo.2017.02.012CrossRefPubMedPubMedCentralGoogle Scholar
  95. Markkanen E (2017) Not breathing is not an option: how to deal with oxidative DNA damage. DNA Repair (Amst) 59:82–105.  https://doi.org/10.1016/j.dnarep.2017.09.007CrossRefGoogle Scholar
  96. Matsubara S, Takasu S, Tsukamoto T, Mutoh M, Masuda S, Sugimura T, Wakabayashi K, Totsuka Y (2012) Induction of glandular stomach cancers in Helicobacter pylori-infected Mongolian gerbils by 1-nitrosoindole-3-acetonitrile. Int J Cancer 130(2):259–266.  https://doi.org/10.1002/ijc.26020CrossRefPubMedGoogle Scholar
  97. Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, Nakao K, Hirayama T, Kohno S (2011) MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer 128(2):361–370.  https://doi.org/10.1002/ijc.25348CrossRefPubMedGoogle Scholar
  98. McDonald SA, Greaves LC, Gutierrez-Gonzalez L, Rodriguez-Justo M, Deheragoda M, Leedham SJ, Taylor RW, Lee CY, Preston SL, Lovell M, Hunt T, Elia G, Oukrif D, Harrison R, Novelli MR, Mitchell I, Stoker DL, Turnbull DM, Jankowski JA, Wright NA (2008) Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Gastroenterology 134(2):500–510.  https://doi.org/10.1053/j.gastro.2007.11.035CrossRefGoogle Scholar
  99. Miftahussurur M, Yamaoka Y, Graham DY (2017) Helicobacter pylori as an oncogenic pathogen, revisited. Expert Rev Mol Med 19:e4.  https://doi.org/10.1017/erm.2017.4CrossRefPubMedGoogle Scholar
  100. Mika D, Guruvayoorappan C (2011) Myeloperoxidase: the yin and yang in tumour progression. J Exp Ther Oncol 9(2):93–100. PMID: 21699016 http://www.oldcitypublishing.com/pdf/2427
  101. Mirzaee V, Molaei M, Shalmani HM, Zali MR (2008) Helicobacter pylori infection and expression of DNA mismatch repair proteins. World J Gastroenterol 14(43):6717–6721.  https://doi.org/10.3748/wjg.14.6717CrossRefPubMedPubMedCentralGoogle Scholar
  102. Morisawa T, Marusawa H, Ueda Y, Iwai A, Okazaki IM, Honjo T, Chiba T (2008) Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression. Int J Cancer 123(12):2735–2740.  https://doi.org/10.1002/ijc.23853CrossRefPubMedGoogle Scholar
  103. Muhammad JS, Nanjo S, Ando T, Yamashita S, Maekita T, Ushijima T, Tabuchi Y, Sugiyama T (2017) Autophagy impairment by Helicobacter pylori-induced methylation silencing of MAP1LC3Av1 promotes gastric carcinogenesis. Int J Cancer 140(10):2272–2283.  https://doi.org/10.1002/ijc.30657CrossRefPubMedGoogle Scholar
  104. Nagata N, Akiyama J, Marusawa H, Shimbo T, Liu Y, Igari T, Nakashima R, Watanabe H, Uemura N, Chiba T (2014) Enhanced expression of activation-induced cytidine deaminase in human gastric mucosa infected by Helicobacter pylori and its decrease following eradication. J Gastroenterol 49(3):427–435.  https://doi.org/10.1007/s00535-013-0808-zCrossRefPubMedGoogle Scholar
  105. Nagini S (2012) Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 4(7):156–169.  https://doi.org/10.4251/wjgo.v4.i7.156CrossRefPubMedPubMedCentralGoogle Scholar
  106. Naito Y, Takagi T, Okada H, Nukigi Y, Uchiyama K, Kuroda M, Handa O, Kokura S, Yagi N, Kato Y, Osawa T, Yoshikawa T (2008) Expression of inducible nitric oxide synthase and nitric oxide-modified proteins in Helicobacter pylori-associated atrophic gastric mucosa. J Gastroenterol Hepatol 23(Suppl 2):S250–S257.  https://doi.org/10.1111/j.1440-1746.2008.05412.xCrossRefPubMedGoogle Scholar
  107. Nakamura J, Tanaka T, Kitajima Y, Noshiro H, Miyazaki K (2014) Methylation-mediated gene silencing as biomarkers of gastric cancer: a review. World J Gastroenterol 20(34):1991–2006.  https://doi.org/10.3748/wjg.i34.11991CrossRefGoogle Scholar
  108. Nathan C, Cunningham-Bussel A (2013) Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol 13(5):349–361.  https://doi.org/10.1038/nri3423CrossRefPubMedPubMedCentralGoogle Scholar
  109. Naumann M, Sokolova O, Tegtmeyer N, Backert S (2017) Helicobacter pylori: a paradigm pathogen for subverting host cell signal transmission. Trends Microbiol 25(4):316–328.  https://doi.org/10.1016/j.tim.2016.12.004CrossRefPubMedGoogle Scholar
  110. Nishimura T (2008) Total number of genome alterations in sporadic gastrointestinal cancer inferred from pooled analyses in the literature. Tumour Biol 29(6):343–350.  https://doi.org/10.1159/000176044CrossRefPubMedGoogle Scholar
  111. Nishizawa T, Suzuki H (2015) Gastric carcinogenesis and underlying molecular mechanisms: Helicobacter pylori and novel targeted therapy. Biomed Res Int 2015:794378.  https://doi.org/10.1155/2015/794378
  112. Niwa T, Toyoda T, Tsukamoto T, Mori A, Tatematsu M, Ushijima T (2013) Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent. Cancer Prev Res (Philadelphia, PA) 6(4):263–270.  https://doi.org/10.1158/1940-6207.capr-12-0369CrossRefGoogle Scholar
  113. Noto JM, Khizanishvili T, Chaturvedi R, Piazuelo MB, Romero-Gallo J, Delgado AG, Khurana SS, Sierra JC, Krishna US, Suarez G, Powell AE, Goldenring JR, Coffey RJ, Yang VW, Correa P, Mills JC, Wilson KT, Peek RM Jr (2013) Helicobacter pylori promotes the expression of Krüppel-like factor 5, a mediator of carcinogenesis, in vitro and in vivo. PLoS ONE 8(1):e54344.  https://doi.org/10.1371/journal.pone.0054344CrossRefPubMedPubMedCentralGoogle Scholar
  114. Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, Yamada G, Azuma T, Hatakeyama M (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA 105(3):1003–1008.  https://doi.org/10.1073/pnas.0711183105CrossRefPubMedGoogle Scholar
  115. Oldani A, Cormont M, Hofman V, Chiozzi V, Oregioni O, Canonici A, Sciullo A, Sommi P, Fabbri A, Ricci V, Boquet P (2009) Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells. PLoS Pathog 5(10):e1000603.  https://doi.org/10.1371/journal.ppat.1000603CrossRefPubMedPubMedCentralGoogle Scholar
  116. Park DI, Park SH, Kim SH, Kim JW, Cho YK, Kim HJ, Sohn CI, Jeon WK, Kim BI, Cho EY, Kim EJ, Chae SW, Sohn JH, Sung IK, Sepulveda AR, Kim JJ (2005) Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein. Helicobacter 10(3):179–184.  https://doi.org/10.1111/j.1523-5378.2005.00309.xCrossRefPubMedGoogle Scholar
  117. Park SY, Yoo EJ, Cho NY, Kim N, Kang GH (2009) Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection. J Pathol 219(4):410–416.  https://doi.org/10.1002/path.2596CrossRefGoogle Scholar
  118. Parsonnet J, Friedman GD, Orentreich N, Vogelman H (1997) Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 40(3):297–301. https://www.ncbi.nlm.nih.gov/pubmed/9135515
  119. Perri F, Cotugno R, Piepoli A, Merla A, Quitadamo M, Gentile A, Pilotto A, Annese V, Andriulli A (2007) Aberrant DNA methylation in non-neoplastic gastric mucosa of Helicobacter pylori infected patients and effect of eradication. Am J Gastroenterol 102(7):1361–1371.  https://doi.org/10.1111/j.1572-0241.2007.01284.xCrossRefPubMedGoogle Scholar
  120. Persson C, Canedo P, Machado JC, El-Omar EM, Forman D (2011) Polymorphisms in inflammatory response genes and their association with gastric cancer: a HuGE systematic review and meta-analyses. Am J Epidemiol 173(3):259–270.  https://doi.org/10.1093/aje/kwq370CrossRefPubMedGoogle Scholar
  121. Pollard TD, Earnshaw WC, Lippincott-Schwartz J (2008) Cell Biology, 2nd edn. Saunders/Elsevier, Philadelphia, p 905Google Scholar
  122. Poplawski T, Chojnacki C, Czubatka A, Klupinska G, Chojnacki J, Blasiak J (2013) Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells. Mol Biol Rep 40(8):5205–5212.  https://doi.org/10.1007/s11033-013-2622-3CrossRefPubMedPubMedCentralGoogle Scholar
  123. Posselt G, Backert S, Wessler S (2013) The functional interplay of Helicobacter pylori factors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal 11:77. https://doi.org/10.1186/1478-811X-11-77
  124. Qian X, Huang C, Cho CH, Hui WM, Rashid A, Chan AO (2008) E-cadherin promoter hypermethylation induced by interleukin-1beta treatment or Helicobacter pylori infection in human gastric cancer cell lines. Cancer Lett 263(1):107–113.  https://doi.org/10.1016/j.canlet.2007.12.023CrossRefPubMedGoogle Scholar
  125. Raza Y, Khan A, Farooqui A, Mubarak M, Facista A, Akhtar SS, Khan S, Kazi JI, Bernstein C, Kazmi SU (2014) Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis. Pathol Oncol Res 20(4):839–846.  https://doi.org/10.1007/s12253-014-9762-1CrossRefPubMedGoogle Scholar
  126. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49(11):1603–1616.  https://doi.org/10.1016/j.freeradbiomed.2010.09.006CrossRefPubMedPubMedCentralGoogle Scholar
  127. Ricci V (2016) Relationship between VacA toxin and host cell autophagy in Helicobacter pylori infection of the human stomach: a few answers, many questions. Toxins (Basel) 8(7): pii E203.  https://doi.org/10.3390/toxins8070203
  128. Rocha GA, Rocha AM, Gomes AD, Faria CL Jr, Melo FF, Batista SA, Fernandes VC, Almeida NB, Teixeira KN, Brito KS, Queiroz DM (2015) STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer. BMC Cancer 15:528.  https://doi.org/10.1186/s12885-015-1533-1CrossRefPubMedPubMedCentralGoogle Scholar
  129. Ronchetti L, Melucci E, De Nicola F, Goeman F, Casini B, Sperati F, Pallocca M, Terrenato I, Pizzuti L, Vici P, Sergi D, Di Lauro L, Amoreo CA, Gallo E, Diodoro MG, Pescarmona E, Vitale I, Barba M, Buglioni S, Mottolese M, Fanciulli M, De Maria R, Maugeri-Saccà M (2017) DNA damage repair and survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy. Int J Cancer 140(11):2587–2595.  https://doi.org/10.1002/ijc.30668CrossRefPubMedGoogle Scholar
  130. Sahan AZ, Hazra TK, Das S (2018) The pivotal role of DNA repair in infection mediated-inflammation and cancer. Front Microbiol 9:663.  https://doi.org/10.3389/fmicb.2018.00663CrossRefPubMedPubMedCentralGoogle Scholar
  131. Santos JC, Ribeiro ML (2015) Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis. World J Gastroenterol 21(30):9021–9037.  https://doi.org/10.3748/wjg.v21.i30.9021CrossRefPubMedPubMedCentralGoogle Scholar
  132. Santos JC, Brianti MT, Almeida VR, Ortega MM, Fischer W, Haas R, Matheu A, Ribeiro ML (2017) Helicobacter pylori infection modulates the expression of miRNAs associated with DNA mismatch repair pathway. Mol Carcinog 56(4):1372–1379.  https://doi.org/10.1002/mc.22590CrossRefPubMedGoogle Scholar
  133. Sasaki T, Kuniyasu H, Luo Y, Kitayoshi M, Tanabe E, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y (2013) Increased phosphorylation of AKT in high-risk gastric mucosa. Anticancer Res 33(8):3295–3300 PMID: 23898095PubMedGoogle Scholar
  134. Satin B, Del Giudice G, Della Bianca V, Dusi S, Laudanna C, Tonello F, Kelleher D, Rappuoli R, Montecucco C, Rossi F (2000) The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. J Exp Med 191:1467–1476.  https://doi.org/10.1084/jem.191.9.1467CrossRefPubMedPubMedCentralGoogle Scholar
  135. Schmees C, Prinz C, Treptau T, Rad R, Hengst L, Voland P, Bauer S, Brenner L, Schmid RM, Gerhard M (2007) Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyltranspeptidase. Gastroenterology 132(5):1820–1833.  https://doi.org/10.1053/j.gastro.2007.02.031CrossRefPubMedGoogle Scholar
  136. Sell S (2011) Infection, stem cells and cancer signals. Curr Pharm Biotechnol 12(2):182–188.  https://doi.org/10.2174/138920111794295675CrossRefPubMedPubMedCentralGoogle Scholar
  137. Serizawa T, Hirata Y, Hayakawa Y, Suzuki N, Sakitani K, Hikiba Y, Ihara S, Kinoshita H, Nakagawa H, Tateishi K, Koike K (2015) Gastric metaplasia induced by Helicobacter pylori is associated with enhanced SOX9 expression via Interleukin-1 signaling. Infect Immun 84(2):562–572.  https://doi.org/10.1128/IAI.01437-15CrossRefPubMedGoogle Scholar
  138. Shahi H, Bahreiny R, Reiisi S (2016) Helicobacter pylori and its virulence factors’ effect on serum oxidative DNA damages in adults with dyspepsia. Acta Med Iran 54(11):704–708 PMID: 28033692PubMedGoogle Scholar
  139. Sheh A, Lee CW, Masumura K, Rickman BH, Nohmi T, Wogan GN, Fox JG, Schauer DB (2010) Mutagenic potency of Helicobacter pylori in the gastric mucosa of mice is determined by sex and duration of infection. Proc Natl Acad Sci USA 107(34):15217–15222.  https://doi.org/10.1073/pnas.1009017107CrossRefPubMedGoogle Scholar
  140. Shimizu T, Marusawa H, Endo Y, Chiba T (2012) Inflammation-mediated genomic instability: roles of activation-induced cytidine deaminase in carcinogenesis. Cancer Sci 103(7):1201–1206.  https://doi.org/10.1111/j.1349-7006.2012.02293.xCrossRefPubMedGoogle Scholar
  141. Shimizu T, Marusawa H, Matsumoto Y, Inuzuka T, Ikeda A, Fujii Y, Minamiguchi S, Miyamoto S, Kou T, Sakai Y, Crabtree JE, Chiba T (2014) Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection. Gastroenterology 147(2):407–417.e3.  https://doi.org/10.1053/j.gastro.2014.04.036CrossRefPubMedGoogle Scholar
  142. Shimizu T, Chiba T, Marusawa H (2017) Helicobacter pylori-mediated genetic instability and gastric carcinogenesis. Curr Top Microbiol Immunol 400:305–323.  https://doi.org/10.1007/978-3-319-50520-6_13CrossRefPubMedGoogle Scholar
  143. Shiotani A, Cen P, Graham DY (2013) Eradication of gastric cancer is now both possible and practical. Semin Cancer Biol 23(6 Pt B):492–501.  https://doi.org/10.1016/j.semcancer.2013.07.004CrossRefPubMedGoogle Scholar
  144. Sigal M, Rothenberg ME, Logan CY, Lee JY, Honaker RW, Cooper RL, Passarelli B, Camorlinga M, Bouley DM, Alvarez G, Nusse R, Torres J, Amieva MR (2015) Helicobacter pylori activates and expands Lgr5(+) stem cells through direct colonization of the gastric glands. Gastroenterology 148(7):1392–1404.  https://doi.org/10.1053/j.gastro.2015.02.049CrossRefPubMedGoogle Scholar
  145. Singh SR (2013) Gastric cancer stem cells: a novel therapeutic target. Cancer Lett 338(1):110–119.  https://doi.org/10.1016/j.canlet.2013.03.035CrossRefPubMedPubMedCentralGoogle Scholar
  146. Slavin T, Neuhausen SL, Rybak C, Solomon I, Nehoray B, Blazer K, Niell-Swiller M, Adamson AW, Yuan YC, Yang K, Sand S, Castillo D, Herzog J, Wu X, Tao S, Chavez T, Woo Y, Chao J, Mora P, Horcasitas D, Weitzel J (2017) Genetic gastric cancer susceptibility in the international clinical cancer genomics community research network. Cancer Genet 216–217:111–119.  https://doi.org/10.1016/j.cancergen.2017.08.001CrossRefPubMedPubMedCentralGoogle Scholar
  147. Smith HC, Bennett RP, Kizilyer A, McDougall WM, Prohaska KM (2012) Functions and regulation of the APOBEC family of proteins. Semin Cell Dev Biol 23(3):258–268.  https://doi.org/10.1016/j.semcdb.2011.10.004CrossRefPubMedGoogle Scholar
  148. Sokolova O, Naumann M (2017) NF-κB signaling in gastric cancer. Toxins (Basel) 9(4):pii E119.  https://doi.org/10.3390/toxins9040119
  149. Sokolova O, Borgmann M, Rieke C, Schweitzer K, Rothkötter HJ, Naumann M (2013) Helicobacter pylori induces type 4 secretion system-dependent, but CagA-independent activation of IκBs and NF-κB/RelA at early time points. Int J Med Microbiol 303(8):548–552.  https://doi.org/10.1016/j.ijmm.2013.07.008CrossRefPubMedGoogle Scholar
  150. Sokolova O, Maubach G, Naumann M (2014) MEKK3 and TAK1 synergize to activate IKK complex in Helicobacter pylori infection. Biochim Biophys Acta 1843(4):715–724.  https://doi.org/10.1016/j.bbamcr.2014.01.006CrossRefPubMedGoogle Scholar
  151. Stairs DB, Kong J, Lynch JP (2010) Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia. Prog Mol Biol Transl Sci 96:231–270.  https://doi.org/10.1016/B978-0-12-381280-3.00010-5CrossRefPubMedPubMedCentralGoogle Scholar
  152. Stracker TH, Roig I, Knobel PA, Marjanović M (2013) The ATM signaling network in development and disease. Front Genet 4:37.  https://doi.org/10.3389/fgene.2013.00037CrossRefPubMedPubMedCentralGoogle Scholar
  153. Sulzbach DE, Oliveira HS, Biolchi V, Richardt Medeiros HR, Bizerra Gandor Jantsch DB, Oliveira Knabben DE, Becker Delving LK, Reckziegel R, Goettert MI, Brum IS, Pozzobon A (2016) Effect of Helicobacter pylori on NFKB1, p38α and TNF-α mRNA expression levels in human gastric mucosa. Exp Ther Med 11(6):2365–2372.  https://doi.org/10.3892/etm.2016.3213CrossRefGoogle Scholar
  154. Tahara E (2004) Genetic pathways of two types of gastric cancer. IARC Sci Publ 157:327–349 PMID: 15055305Google Scholar
  155. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y, Wang TC (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27(5):1006–1020.  https://doi.org/10.1002/stem.30CrossRefPubMedPubMedCentralGoogle Scholar
  156. Takeda Y, Yashima K, Hayashi A, Sasaki S, Kawaguchi K, Harada K, Murawaki Y, Ito H (2012) Expression of AID, P53, and Mlh1 proteins in endoscopically resected differentiated-type early gastric cancer. World J Gastrointest Oncol 4(6):131–137.  https://doi.org/10.4251/wjgo.v4.i6.131CrossRefPubMedPubMedCentralGoogle Scholar
  157. Tamura G (2006) Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol 12(2):192–198.  https://doi.org/10.3748/wjg.v12.i2.192CrossRefPubMedPubMedCentralGoogle Scholar
  158. Tegtmeyer N, Zabler D, Schmidt D, Hartig R, Brandt S, Backert S (2009) Importance of EGF receptor, HER2/Neu and Erk1/2 kinase signalling for host cell elongation and scattering induced by the Helicobacter pylori CagA protein: antagonistic effects of the vacuolating cytotoxin VacA. Cell Microbiol 11(3):488–505.  https://doi.org/10.1111/j.1462-5822.2008.01269.xCrossRefPubMedGoogle Scholar
  159. Tegtmeyer N, Neddermann M, Asche CI, Backert S (2017) Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagA. Mol Microbiol 105(3):358–372.  https://doi.org/10.1111/mmi.13707CrossRefPubMedGoogle Scholar
  160. Terebiznik MR, Raju D, Vázquez CL, Torbricki K, Kulkarni R, Blanke SR, Yoshimori T, Colombo MI, Jones NL (2009) Effect of Helicobacter pylori’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells. Autophagy 5(3):370–379.  https://doi.org/10.4161/auto.5.3.7663CrossRefPubMedGoogle Scholar
  161. Toller IM, Neelsen KJ, Steger M, Hartung ML, Hottiger MO, Stucki M, Kalali B, Gerhard M, Sartori AA, Lopes M, Müller A (2011) Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proc Natl Acad Sci USA 108(36):14944–14949.  https://doi.org/10.1073/pnas.1100959108CrossRefPubMedGoogle Scholar
  162. Touati E (2010) When bacteria become mutagenic and carcinogenic: lessons from Helicobacter pylori. Mutat Res 703(1):66–70.  https://doi.org/10.1016/j.mrgentox.2010.07.014CrossRefPubMedGoogle Scholar
  163. Touati E, Michel V, Thiberge JM, Wuscher N, Huerre M, Labigne A (2003) Chronic Helicobacter pylori infections induce gastric mutations in mice. Gastroenterology 124(5):1408–1419.  https://doi.org/10.1016/S0016-5085(03)00266-XCrossRefPubMedGoogle Scholar
  164. Toyoda T, Tsukamoto T, Hirano N, Mizoshita T, Kato S, Takasu S, Ban H, Tatematsu M (2008) Synergistic upregulation of inducible nitric oxide synthase and cyclooxygenase-2 in gastric mucosa of Mongolian gerbils by a high-salt diet and Helicobacter pylori infection. Histol Histopathol 23:593–599.  https://doi.org/10.14670/HH-23.593
  165. Tsai YC, Li PY, Chen CC, Liu YC (2013) Is the oxidative DNA damage level of human lymphocyte correlated with the antioxidant capacity of serum or the base excision repair activity of lymphocyte? Oxid Med Cell Longev 2013:237583.  https://doi.org/10.1155/2013/237583CrossRefPubMedPubMedCentralGoogle Scholar
  166. Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, Nagano O,  Matsuzaki J, Hibi T (2012) Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host & Microbe 12(6):764–777.  https://doi.org/10.1016/j.chom.2012.10.014
  167. Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, Betz KS, Penz-Oesterreicher M, Bjorkdahl O, Fox JG, Wang TC (2008) Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14(5):408–419.  https://doi.org/10.1016/j.ccr.2008.10.011CrossRefPubMedPubMedCentralGoogle Scholar
  168. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, Yoshida K, Sasaki H, Nomura S, Seto Y, Kaminishi M, Calin GA, Croce CM (2010) Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol 11(2):136–146.  https://doi.org/10.1016/S1470-2045(09)70343-2CrossRefPubMedGoogle Scholar
  169. Uehara T, Ma D, Yao Y, Lynch JP, Morales K, Ziober A, Feldman M, Ota H, Sepulveda AR (2013) Helicobacter pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer. Dig Dis Sci 58(1):140–149.  https://doi.org/10.1007/s10620-012-2360-8CrossRefPubMedGoogle Scholar
  170. Ushijima T, Hattori N (2012) Molecular pathways: involvement of Helicobacter pylori-triggered inflammation in the formation of an epigenetic field defect, and its usefulness as cancer risk and exposure markers. Clin Cancer Res 18(4):923–929.  https://doi.org/10.1158/1078-0432.CCR-11-2011CrossRefGoogle Scholar
  171. Ushijima T, Nakajima T, Maekita T (2006) DNA methylation as a marker for the past and future. J Gastroenterol 41(5):401–407.  https://doi.org/10.1007/s00535-006-1846-6CrossRefPubMedGoogle Scholar
  172. Valenzuela MA, Canales J, Corvalán AH, Quest AF (2015) Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World J Gastroenterol 21(45):12742–12756.  https://doi.org/10.3748/wjg.v21.i45.12742CrossRefPubMedPubMedCentralGoogle Scholar
  173. van Loon B, Markkanen E, Hübscher U (2010) Oxygen as a friend and enemy: how to combat the mutational potential of 8-oxo-guanine. DNA Repair (Amst) 9(6):604–616.  https://doi.org/10.1016/j.dnarep.2010.03.004CrossRefGoogle Scholar
  174. Varon C, Dubus P, Mazurier F, Asencio C, Chambonnier L, Ferrand J, Giese A, Senant-Dugot N, Carlotti M, Mégraud F (2012) Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice. Gastroenterology 142(2):281–291.  https://doi.org/10.1053/j.gastro.2011.10.036CrossRefPubMedGoogle Scholar
  175. Velho S, Fernandes MS, Leite M, Figueiredo C, Seruca R (2014) Causes and consequences of microsatellite instability in gastric carcinogenesis. World J Gastroenterol 20(44):16433–16442.  https://doi.org/10.3748/wjg.v20.i44.16433CrossRefPubMedPubMedCentralGoogle Scholar
  176. Vidal AE, Hickson ID, Boiteux S, Radicella JP (2001) Mechanism of stimulation of the DNA glycosylase activity of hOGG1 by the major human AP endonuclease: bypass of the AP lyase activity step. Nucleic Acids Res 29(6):1285–1292. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC29755/
  177. Virchow R (1863) Die Krankhaften Geschwülste. Vorlesungen über Pathologie. Verlag von August Hirschwald, Berlin, p 543Google Scholar
  178. Wada Y, Takemura K, Tummala P, Uchida K, Kitagaki K, Furukawa A, Ishige Y, Ito T, Hara Y, Suzuki T, Mimuro H, Board PG, Eishi Y (2018) Helicobacter pylori induces somatic mutations in TP53 via overexpression of CHAC1 in infected gastric epithelial cells. FEBS Open Bio 8(4):671–679.  https://doi.org/10.1002/2211-5463.12402CrossRefPubMedPubMedCentralGoogle Scholar
  179. Wakamatsu Y, Sakamoto N, Oo HZ, Naito Y, Uraoka N, Anami K, Sentani K, Oue N, Yasui W (2012) Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int 62(2):112–119.  https://doi.org/10.1111/j.1440-1827.2011.02760.xCrossRefPubMedGoogle Scholar
  180. Waldum HL, Öberg K, Sørdal ØF, Sandvik AK, Gustafsson BI, Mjønes P, Fossmark R (2018) Not only stem cells, but also mature cells, particularly neuroendocrine cells, may develop into tumours: time for a paradigm shift. Therap Adv Gastroenterol 11:1756284818775054.  https://doi.org/10.1177/1756284818775054CrossRefPubMedPubMedCentralGoogle Scholar
  181. Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12:685–698.  https://doi.org/10.1038/nrc3365CrossRefPubMedPubMedCentralGoogle Scholar
  182. Wang J, Xu L, Shi R, Huang X, Li SW, Huang Z, Zhang G (2011) Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion 83(4):253–260.  https://doi.org/10.1159/000280318CrossRefPubMedGoogle Scholar
  183. Wang XW, Wu Y, Wang D, Qin ZF (2014) MicroRNA network analysis identifies key microRNAs and genes associated with precancerous lesions of gastric cancer. Genet Mol Res 13(4):8695–8703.  https://doi.org/10.4238/2014.October.27.10CrossRefPubMedGoogle Scholar
  184. Wang YK, Chiang WC, Kuo FC, Wu MC, Shih HY, Wang SSW, Liu CJ, Chen YH, Wu DC, Su WW, Huang YL (2018) Levels of malondialdehyde in the gastric juice: its association with Helicobacter pylori infection and stomach diseases. Helicobacter 23(2):e12460.  https://doi.org/10.1111/hel.12460CrossRefPubMedGoogle Scholar
  185. Ward MH, Cross AJ, Abnet CC, Sinha R, Markin RS, Weisenburger DD (2012) Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach. Eur J Cancer Prev 21(2):134–138.  https://doi.org/10.1097/CEJ.0b013e32834c9b6cCrossRefPubMedPubMedCentralGoogle Scholar
  186. Wei J, Noto J, Zaika E, Romero-Gallo J, Correa P, El-Rifai W, Peek RM, Zaika A (2012) Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses. Proc Natl Acad Sci USA 109(38):E2543–E2550.  https://doi.org/10.1073/pnas.1205664109CrossRefPubMedGoogle Scholar
  187. Woerner SM, Yuan YP, Benner A, Korff S, von Knebel Doeberitz M, Bork P (2010) SelTarbase, a database of human mononucleotide-microsatellite mutations and their potential impact to tumorigenesis and immunology. Nucleic Acids Res 38:D682–D689.  https://doi.org/10.1093/nar/gkp839CrossRefPubMedGoogle Scholar
  188. 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. Biochem Biophys Res Commun 369(2):526–531.  https://doi.org/10.1016/j.bbrc.2008.02.073CrossRefPubMedGoogle Scholar
  189. Yadav VK, DeGregori J, De S (2016) The landscape of somatic mutations in protein coding genes in apparently benign human tissues carries signatures of relaxed purifying selection. Nucleic Acids Res 44(5):2075–2084.  https://doi.org/10.1093/nar/gkw086CrossRefPubMedPubMedCentralGoogle Scholar
  190. Yamashita K, Sakuramoto S, Watanabe M (2011) Genomic and epigenetic profiles of gastric cancer: potential diagnostic and therapeutic applications. Surg Today 41(1):24–38.  https://doi.org/10.1007/s00595-010-4370-5CrossRefPubMedGoogle Scholar
  191. Yan YG, Zhao G, Ma JP, Cai SR, Zhan WH (2008) Effects of different Helicobacter pylori culture filtrates on growth of gastric epithelial cells. World J Gastroenterol 14(23):3745–3749.  https://doi.org/10.3748/wjg.14.3745CrossRefPubMedPubMedCentralGoogle Scholar
  192. Yanaoka K, Oka M, Yoshimura N, Deguchi H, Mukoubayashi C, Enomoto S, Maekita T, Inoue I, Ueda K, Utsunomiya H, Iguchi M, Tamai H, Fujishiro M, Nakamura Y, Tsukamoto T, Inada K, Takeshita T, Ichinose M (2010) Preventive effects of etodolac, a selective cyclooxygenase-2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori-negative precancerous lesion. Int J Cancer 126(6):1467–1473.  https://doi.org/10.1002/ijc.24862CrossRefPubMedGoogle Scholar
  193. Yang B, Fu X, Shao L, Ding Y, Zeng D (2014) Aberrant expression of SIRT3 is conversely correlated with the progression and prognosis of human gastric cancer. Biochem Biophys Res Commun 443(1):156–160.  https://doi.org/10.1016/j.bbrc.2013.11.068CrossRefPubMedGoogle Scholar
  194. Yeniova AO, Uzman M, Kefeli A, Basyigit S, Ata N, Dal K, Guresci S, Nazligul Y (2015) Serum 8 Hydroxydeoxyguanosine and Cytotoxin Associated Gene A as Markers for Helicobacter pylori Infection. Asian Pac J Cancer Prev 16(13):5199–5203 PMID: 26225653Google Scholar
  195. Zhang LJ, Wang SY, Huo XH, Zhu ZL, Chu JK, Ma JC, Cui DS, Gu P, Zhao ZR, Wang MW, Yu J (2009) Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions. World J Gastroenterol 15(22):2731–2738.  https://doi.org/10.3748/wjg.15.2731CrossRefPubMedPubMedCentralGoogle Scholar
  196. Zhang XS, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G, Sticht H, Backert S, Blaser MJ (2015) A specific A/T polymorphism in western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interaction. PloS Pathog 11:e1004621. https://doi.org/10.1371/journal.ppat.1004621

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Experimental Internal MedicineOtto von Guericke UniversityMagdeburgGermany

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