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Gastric Tumorigenesis: Role of Inflammation and Helicobacter pylori

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Gastric Cancer In The Precision Medicine Era

Part of the book series: Current Clinical Pathology ((CCPATH))

Abstract

It is estimated that chronic inflammation contributes to nearly 25% of human cancers. Inflammation of the gastric mucosa is dependent on various modulatory components such as microbes, environment, and host predisposition. Helicobacter pylori (H. pylori) can initiate and sustain gastric inflammation by its virulence factors as well as by altered cellular pathways that are involved in the restoration of the tissue homeostasis after infection. Indeed, in an attempt to repair injured mucosa, immune system may contribute to gastric cancer development through its physiological pro-inflammatory and anti-inflammatory activities which, particularly in a setting of chronic antigenic stimulation, can turn in pro-tumorigenic effects. In this chapter some of the mechanisms connected to H. pylori-related inflammation will be depicted, also focusing on microenvironmental cellular and soluble driving factors recently highlighted in gastric cancer promotion.

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References

  1. Reese DM. Fundamentals-Rudolf Virchow and modern medicine. West J Med. 1998;169(2):105–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Orange M, Reuter U, Hobohm U. Coley’s lessons remembered: augmenting mistletoe therapy. Integr Cancer Ther. 2016;15(4):502–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  4. Blaser MJ, Atherton JC. Helicobacter pylori persistence: biology and disease. J Clin Invest. 2004;113(3):321–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest. 2009;119(9):2475–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Schistosomes, liver flukes and helicobacter pylori, vol. 61. Lyon: International Agency for Research on Cancer; 1994. p. 177.

    Google Scholar 

  7. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118(12):3030–44.

    Article  CAS  PubMed  Google Scholar 

  8. Chmiela M, Wadstrom T, Folkesson H, et al. Anti-Lewis X antibody and Lewis X-anti-Lewis X immune complexes in Helicobacter pylori infection. Immunol Lett. 1998;61(2–3):119–25.

    Article  CAS  PubMed  Google Scholar 

  9. Chmiela M, Gonciarz W. Molecular mimicry in Helicobacter pylori infections. World J Gastroenterol. 2017;23(22):3964–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Correa P, Piazuelo MB. The gastric precancerous cascade. J Dig Dis. 2012;13(1):2–9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Burucoa C, Axon A. Epidemiology of Helicobacter pylori infection. Helicobacter. 2017;22 Suppl 1:1–5.

    Google Scholar 

  12. Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2(1):28–37.

    Article  CAS  PubMed  Google Scholar 

  13. Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23:713–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Suerbaum S, Josenhans C. Helicobacter pylori evolution and phenotypic diversification in a changing host. Nat Rev Microbiol. 2007;5:441–52.

    Article  CAS  PubMed  Google Scholar 

  15. Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol. 2006;1:63–96.

    Article  CAS  PubMed  Google Scholar 

  16. Saberi S, Douraghi M, Azadmanesh K, et al. A potential association between Helicobacter pylori CagA EPIYA and multimerization motifs with cytokeratin 18 cleavage rate during early apoptosis. Helicobacter. 2012;17(5):350–7.

    Article  CAS  PubMed  Google Scholar 

  17. Greenfield LK, Jones NL. Modulation of autophagy by Helicobacter pylori and its role in gastric carcinogenesis. Trends Microbiol. 2013;21(11):602–12.

    Article  CAS  PubMed  Google Scholar 

  18. El-Omar EM, Rabkin CS, Gammon MD, et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology. 2003;124(5):1193–201.

    Article  CAS  PubMed  Google Scholar 

  19. El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404(6776):398–402. Erratum in: Nature 2001 Jul 5;412(6842):99.

    Article  CAS  PubMed  Google Scholar 

  20. Machado JC, Pharoah P, Sousa S, et al. Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology. 2001;121(4):823–9.

    Article  CAS  PubMed  Google Scholar 

  21. Lee WP, Tai DI, Lan KH, et al. The -251T allele of the interleukin-8 promoter is associated with increased risk of gastric carcinoma featuring diffuse-type histopathology in Chinese population. Clin Cancer Res. 2005;11(18):6431–41.

    Article  CAS  PubMed  Google Scholar 

  22. Taguchi A, Ohmiya N, Shirai K, et al. Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomark Prev. 2005;14(11 Pt 1):2487–93.

    Article  CAS  Google Scholar 

  23. De Bernard M, D’Elios MM. The immune modulating activity of the Helicobacter pylori HP-NAP: friend or foe? Toxicon. 2010;56(7):1186–92.

    Article  PubMed  CAS  Google Scholar 

  24. Palframan SL, Kwok T, Gabriel K. Vacuolating cytotoxin A (VacA), a key toxin for Helicobacter pylori pathogenesis. Front Cell Infect Microbiol. 2012;2:92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Barrozo RM, Cooke CL, Hansen LM, et al. Functional plasticity in the type IV secretion system of Helicobacter pylori. PLoS Pathogens. 2013;9(2):e1003189.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Figura N, Marano L, Moretti E, et al. Helicobacter pylori infection and gastric carcinoma: not all the strains and patients are alike. World J Gastrointest Oncol. 2016;8(1):40–54.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wang CA, Liu YC, Du SY, et al. Helicobacter pylori neutrophil-activating protein promotes myeloperoxidase release from human neutrophils. Biochem Biophys Res Commun. 2008;377(1):52–6.

    Article  CAS  PubMed  Google Scholar 

  28. Petersson C, Forsberg M, Aspholm M, et al. Helicobacter pylori SabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein. Med Microbiol Immunol. 2006;195(4):195–206.

    Article  CAS  PubMed  Google Scholar 

  29. Montemurro P, Nishioka H, Dundon WG, et al. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a potent stimulant of mast cells. Eur J Immunol. 2002;32(3):671–6.

    Article  CAS  PubMed  Google Scholar 

  30. Brisslert M, Enarsson K, Lundin S, et al. Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP. FEMS Microbiol Lett. 2005;249(1):95–103.

    Article  CAS  PubMed  Google Scholar 

  31. Polenghi A, Bossi F, Fischetti F, et al. The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo. J Immunol. 2007;178(3):1312–20.

    Article  CAS  PubMed  Google Scholar 

  32. Amedei A, Cappon A, Codolo G, et al. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. J Clin Invest. 2006;116(4):1092–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ricci V, Giannouli M, Romano M, et al. Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role. World J Gastroenterol. 2014;20(3):630–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Schmees C, Prinz C, Treptau T, et al. Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology. 2007;132(5):1820–33.

    Article  CAS  PubMed  Google Scholar 

  35. Oertli M, Noben M, Engler DB, et al. Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proc Natl Acad Sci U S A. 2013;110(8):3047–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Backert S, Tegtmeyer N, Fischer W. Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system. Future Microbiol. 2015;10(6):955–65.

    Article  CAS  PubMed  Google Scholar 

  37. Hatakeyama M. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell Host Microbe. 2014;15(3):306–16.

    Article  CAS  PubMed  Google Scholar 

  38. Churin Y, Al-Ghoul L, Kepp O, et al. Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol. 2003;161(2):249–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mimuro H, Suzuki T, Tanaka J, et al. Grb2 is a key mediator of helicobacter pylori CagA protein activities. Mol Cell. 2002;10(4):745–55.

    Article  CAS  PubMed  Google Scholar 

  40. Murata-Kamiya N, Kurashima Y, Teishikata Y, et al. Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 2007;26(32):4617–26.

    Article  CAS  PubMed  Google Scholar 

  41. Saadat I, Higashi H, Obuse C, et al. Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature. 2007;447(7142):330–3.

    Article  CAS  PubMed  Google Scholar 

  42. Tsugawa H, Suzuki H, Saya H, et al. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe. 2012;12(6):764–77.

    Article  CAS  PubMed  Google Scholar 

  43. Ishimoto T, Oshima H, Oshima M, et al. CD44+ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis. Cancer Sci. 2010;101(3):673–8.

    Article  CAS  PubMed  Google Scholar 

  44. Garay J, Piazuelo MB, Majumdar S, et al. The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice. Cancer Lett. 2016;371(1):90–8.

    Article  CAS  PubMed  Google Scholar 

  45. Hirata K, Suzuki H, Imaeda H, et al. CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence. Br J Cancer. 2013;109(2):379–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wakamatsu Y, Sakamoto N, Oo HZ, et al. Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int. 2012;62(2):112–9.

    Article  PubMed  Google Scholar 

  47. Watanabe T, Asano N, Fichtner-Feigl S, et al. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J Clin Invest. 2010;120(5):1645–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang G, Lo LF, Forsberg LS, et al. Helicobacter pylori peptidoglycan modifications confer lysozyme resistance and contribute to survival in the host. MBio. 2012;3(6):e00409–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wang G, Maier SE, Lo LF, et al. Peptidoglycan deacetylation in Helicobacter pylori contributes to bacterial survival by mitigating host immune responses. Infect Immun. 2010;78(11):4660–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kalali B, Mejías-Luque R, Javaheri A, et al. H. pylori virulence factors: influence on immune system and pathology. Mediators Inflamm. 2014;2014:426309.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Kim JM, Kim JS, Lee JY, et al. Vacuolating cytotoxin in Helicobacter pylori water-soluble proteins upregulates chemokine expression in human eosinophils via Ca2+ influx, mitochondrial reactive oxygen intermediates, and NF-kappaB activation. Infect Immun. 2007;75(7):3373–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Takeshima E, Tomimori K, Takamatsu R, et al. Helicobacter pylori VacA activates NF-κB in T cells via the classical but not alternative pathway. Helicobacter. 2009;14(4):271–9.

    Article  CAS  PubMed  Google Scholar 

  53. Muller A, Oertli M, Arnold IC. H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection. Cell Commun Signal. 2011;9(1):25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rizzuti D, Ang M, Sokollik C, et al. Helicobacter pylori inhibits dendritic cell maturation via interleukin-10-mediated activation of the signal transducer and activator of transcription 3 pathway. J Innate Immun. 2015;7(2):199–211.

    Article  CAS  PubMed  Google Scholar 

  55. Shimizu T, Chiba T, Marusawa H. Helicobacter pylori-mediated genetic instability and gastric carcinogenesis. Curr Top Microbiol Immunol. 2017;400:305–23.

    CAS  PubMed  Google Scholar 

  56. Ushijima T, Hattori N. 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. 2012;18(4):923–9.

    Article  CAS  PubMed  Google Scholar 

  57. Pignatelli B, Bancel B, Plummer M, et al. Helicobacter pylori eradication attenuates oxidative stress in human gastric mucosa. Am J Gastroenterol. 2001;96(6):1758–66.

    Article  CAS  PubMed  Google Scholar 

  58. Mera R, Fontham ET, Bravo LE, et al. Long term follow up of patients treated for Helicobacter pylori infection. Gut. 2005;54(11):1536–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Massarrat S, Haj-Sheykholeslami A, Mohamadkhani A, et al. Precancerous conditions after H. pylori eradication: a randomized double blind study in first degree relatives of gastric cancer patients. Arch Iran Med. 2012;15(11):664–9.

    PubMed  Google Scholar 

  60. Chen HN, Wang Z, Li X, Zhou ZG. Helicobacter pylori eradication cannot reduce the risk of gastric cancer in patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis. Gastric Cancer. 2016;19(1):166–75.

    Article  PubMed  Google Scholar 

  61. Koeppel M, Garcia-Alcalde F, Glowinski F, et al. Helicobacter pylori infection causes characteristic DNA damage patterns in human cells. Cell Rep. 2015;11(11):1703–13.

    Article  CAS  PubMed  Google Scholar 

  62. Lee WP, Hou MC, Lan KH, et al. 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. 2016;606:90–8.

    Article  CAS  PubMed  Google Scholar 

  63. Kawanishi S, Ohnishi S, Ma N, et al. Crosstalk between DNA damage and inflammation in the multiple steps of carcinogenesis. Int J Mol Sci. 2017;18(8):E1808.

    Article  PubMed  CAS  Google Scholar 

  64. Baek HY, Lim JW, Kim H, et al. Oxidative-stress-related proteome changes in Helicobacter pylori-infected human gastric mucosa. Biochem J. 2004;379(Pt 2):291–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang FY, Chan AO, Rashid A, et al. Helicobacter pylori induces promoter methylation of E-cadherin via interleukin-1β activation of nitric oxide production in gastric cancer cells. Cancer. 2012;118(20):4969–80.

    Article  CAS  PubMed  Google Scholar 

  66. Hanada K, Uchida T, Tsukamoto Y, et al. Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infect Immun. 2014;82(10):4182–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Shimizu T, Marusawa H, Matsumoto Y, et al. Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection. Gastroenterology. 2014;147(2):407–17.e3.

    Article  CAS  PubMed  Google Scholar 

  68. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yuan X, Zhou Y, Wang W, et al. Activation of TLR4 signaling promotes gastric cancer progression by inducing mitochondrial ROS production. Cell Death Dis. 2013;4:e794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cha B, Lim JW, Kim KH, et al. HSP90beta interacts with Rac1 to activate NADPH oxidase in Helicobacter pylori-infected gastric epithelial cells. Int J Biochem Cell Biol. 2010;42(9):1455–61.

    Article  CAS  PubMed  Google Scholar 

  71. Handa O, Naito Y, Yoshikawa T. CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling. Biochem Pharmacol. 2007;73(11):1697–702.

    Article  CAS  PubMed  Google Scholar 

  72. Chaturvedi R, Asim M, Romero-Gallo J, et al. Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA. Gastroenterology. 2011;141(5):1696–708.e1–2.

    Article  CAS  PubMed  Google Scholar 

  73. Vitkute J, Stankevicius K, Tamulaitiene G, et al. Specificities of eleven different DNA methyltransferases of Helicobacter pylori strain 26695. J Bacteriol. 2001;183(2):443–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Niwa T, Tsukamoto T, Toyoda T, et al. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res. 2010;70(4):1430–40.

    Article  CAS  PubMed  Google Scholar 

  75. Maeda M, Moro H, Ushijima T. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway. Gastric Cancer. 2017;20(Suppl 1):8–15.

    Article  CAS  PubMed  Google Scholar 

  76. Matsumoto Y, Marusawa H, Kinoshita K, et al. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med. 2007;13(4):470–6.

    Article  CAS  PubMed  Google Scholar 

  77. Nagata N, Akiyama J, Marusawa H, et al. Enhanced expression of activation-induced cytidine deaminase in human gastric mucosa infected by Helicobacter pylori and its decrease following eradication. J Gastroenterol. 2014;49(3):427–35.

    Article  CAS  PubMed  Google Scholar 

  78. Matsumoto Y, Marusawa H, Kinoshita K, et al. Up-regulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. Gastroenterology. 2010;139(6):1984–94.

    Article  CAS  PubMed  Google Scholar 

  79. Machado AM, Figueiredo C, Touati E, et al. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells. Clin Cancer Res. 2009;15(9):2995–3002.

    Article  CAS  PubMed  Google Scholar 

  80. Kim JJ, Tao H, Carloni E, et al. Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology. 2002;123(2):542–53.

    Article  CAS  PubMed  Google Scholar 

  81. Park DI, Park SH, Kim SH, et al. Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein. Helicobacter. 2005;10(3):179–84.

    Article  CAS  PubMed  Google Scholar 

  82. Toller IM, Neelsen KJ, Steger M, et al. Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proc Natl Acad Sci U S A. 2011;108(36):14944–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hartung ML, Gruber DC, Koch KN, et al. H. pylori-induced DNA Strand breaks are introduced by nucleotide excision repair endonucleases and promote NF-κB target gene expression. Cell Rep. 2015;13(1):70–9.

    Article  CAS  PubMed  Google Scholar 

  84. Terebiznik MR, Raju D, Vázquez CL, et al. Effect of Helicobacter pylori’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells. Autophagy. 2009;5(3):370–9.

    Article  CAS  PubMed  Google Scholar 

  85. Wang YH, Wu JJ, Lei HY. The autophagic induction in Helicobacter pylori-infected macrophage. Exp Biol Med (Maywood). 2009;234(2):171–80.

    Article  CAS  Google Scholar 

  86. Yang X, Yu DD, Yan F, et al. The role of autophagy induced by tumor microenvironment in different cells and stages of cancer. Cell Biosci. 2015;5:14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Polk DB, Peek RM Jr. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010;10(6):403–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Raju D, Jones NL. Methods to monitor autophagy in H. pylori vacuolating cytotoxin A (VacA)-treated cells. Autophagy. 2010;6(1):138–43.

    Article  CAS  PubMed  Google Scholar 

  89. Mathew R, Karp CM, Beaudoin B, et al. Autophagy suppresses tumorigenesis through elimination of p62. Cell. 2009;137(6):1062–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mohamed A, Ayman A, Deniece J, et al. P62/biquitin IHC expression correlated with clinicopathologic parameters and outcome in gastrointestinal carcinomas. Front Oncol. 2015;5:70.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Gump JM, Thorburn A. Autophagy and apoptosis: what is the connection? Trends Cell Biol. 2011;21(7):387–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Eisenberg-Lerner A, Bialik S, Simon HU, et al. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009;16(7):966–75.

    Article  CAS  PubMed  Google Scholar 

  93. Xu MY, Lee DH, Joo EJ, et al. Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells. Food Chem Toxicol. 2013;59:703–8. https://doi.org/10.1016/j.fct.2013.06.059. Epub 2013 Jul 9.

    Article  CAS  PubMed  Google Scholar 

  94. Lim SC, Han SI. Ursodeoxycholic acid effectively kills drug-resistant gastric cancer cells through induction of autophagic death. Oncol Rep. 2015;34(3):1261–8.

    Article  CAS  PubMed  Google Scholar 

  95. Mukhopadhyay S, Panda PK, Sinha N, et al. Autophagy and apoptosis: where do they meet? Apoptosis. 2014;19(4):555–66.

    Article  CAS  PubMed  Google Scholar 

  96. Karki R, Man SM, Kanneganti TD. Inflammasomes and Cancer. Cancer Immunol Res. 2017;5(2):94–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jorgensen I, Rayamajhi M, Miao EA. Programmed cell death as a defence against infection. Nat Rev Immunol. 2017;17(3):151–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12(4):253–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. O’Keeffe J, Moran AP. Conventional, regulatory, and unconventional T cells in the immunologic response to Helicobacter pylori. Helicobacter. 2008;13(1):1–19.

    Article  PubMed  Google Scholar 

  100. Choi YJ, Kim N, Chang H, et al. Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells. Carcinogenesis. 2015;36(5):553–63.

    Article  CAS  PubMed  Google Scholar 

  101. Mesali H, Ajami A, Hussein-Nattaj H, et al. Regulatory T cells and myeloid-derived suppressor cells in patients with peptic ulcer and gastric cancer. Iran J Immunol. 2016;13(3):167–77.

    PubMed  Google Scholar 

  102. Bockerstett KA, DiPaolo RJ. Regulation of gastric carcinogenesis by inflammatory cytokines. Cell Mol Gastroenterol Hepatol. 2017;4(1):47–53.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Jafarzadeh A, Larussa T, Nemati M, et al. T cell subsets play an important role in the determination of the clinical outcome of Helicobacter pylori infection. Microb Pathog. 2018. pii: S0882–4010(16)30548–4.

    Google Scholar 

  104. González CA, Figueiredo C, Lic CB, et al. Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long-term follow-up in a high-risk area in Spain. Am J Gastroenterol. 2011;106(5):867–74.

    Article  PubMed  CAS  Google Scholar 

  105. Hanada K, Yamaoka Y. Genetic battle between Helicobacter pylori and humans. The mechanism underlying homologous recombination in bacteria, which can infect human cells. Microbes Infect. 2014;16(10):833–9.

    Article  CAS  PubMed  Google Scholar 

  106. Rubin EJ, Trent MS. Colonize, evade, flourish: how glyco-conjugates promote virulence of Helicobacter pylori. Gut Microbes. 2013;4(6):439–53.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Ferreira JA, Magalhães A, Gomes J, et al. Protein glycosylation in gastric and colorectal cancers: toward cancer detection and targeted therapeutics. Cancer Lett. 2017;387:32–45.

    Article  CAS  PubMed  Google Scholar 

  108. Karita M, Blaser MJ. Acid-tolerance response in Helicobacter pylori and differences between cagA+ and cagA- strains. J Infect Dis. 1998;178:213–9.

    Article  CAS  PubMed  Google Scholar 

  109. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347:1175–86.

    Article  CAS  PubMed  Google Scholar 

  110. Figura N, Trabalzini L, Mini R, et al. Inactivation of Helicobacter pylori cagA gene affects motility. Helicobacter. 2004;9:185–93.

    Article  CAS  PubMed  Google Scholar 

  111. Basaglia G, Sperandio P, Tomasini ML, et al. Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates. J Chemother. 2004;16(5):504–6.

    Article  CAS  PubMed  Google Scholar 

  112. De Paoli P, Tomasini ML, Basaglia G. The predictive value of Helicobacter pylori in-vitro metronidazole resistance. Clin Microbiol Infect. 2004;10(12):1105–6.

    Article  PubMed  Google Scholar 

  113. Tomasini ML, Zanussi S, Sozzi M, et al. Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens. J Clin Microbiol. 2003;41(3):976–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sozzi M, Crosatti M, Kim SK, et al. Heterogeneity of Helicobacter pylori cag genotypes in experimentally infected mice. FEMS Microbiol Lett. 2001;203(1):109–14.

    Article  CAS  PubMed  Google Scholar 

  115. Figura N, Valassina M, Moretti E, et al. Histological variety of gastric carcinoma and Helicobacter pylori cagA and vacA polymorphism. Eur J Gastroenterol Hepatol. 2015;27(9):1017–21.

    Article  CAS  PubMed  Google Scholar 

  116. Repetto O, Zanussi S, Casarotto M, et al. Differential proteomics of Helicobacter pylori associated with autoimmune atrophic gastritis. Mol Med. 2014;20:57–71.

    Article  PubMed  CAS  Google Scholar 

  117. Bernardini G, Figura N, Ponzetto A, et al. Application of proteomics to the study of Helicobacter pylori and implications for the clinic. Expert Rev Proteomics. 2017;14(6):477–90.

    Article  CAS  PubMed  Google Scholar 

  118. Sozzi M, Valentini M, Figura N, et al. Atrophic gastritis and intestinal metaplasia in Helicobacter pylori infection: the role of CagA status. Am J Gastroenterol. 1998;93(3):375–9.

    Article  CAS  PubMed  Google Scholar 

  119. Sozzi M, Tomasini ML, Vindigni C, et al. Heterogeneity of cag genotypes and clinical outcome of Helicobacter pylori infection. J Lab Clin Med. 2005;146(5):262–70.

    Article  CAS  PubMed  Google Scholar 

  120. Korneev KV, Atretkhany KN, Drutskaya MS, et al. TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis. Cytokine. 2017;89:127–35.

    Article  CAS  PubMed  Google Scholar 

  121. Pachathundikandi SK, Müller A, Backert S. Inflammasome activation by Helicobacter pylori and its implications for persistence and immunity. Curr Top Microbiol Immunol. 2016;397:117–31.

    CAS  PubMed  Google Scholar 

  122. Kohyama M, Saijyo K, Hayasida M, et al. Direct activation of human CD8+ cytotoxic T lymphocytes by interleukin-18. Jpn J Cancer Res. 1998;89(10):1041–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Palma G, Barbieri A, Bimonte S, et al. Interleukin 18: friend or foe in cancer. Biochim Biophys Acta. 2013;1836(2):296–303.

    CAS  PubMed  Google Scholar 

  124. Terme M, Ullrich E, Aymeric L, et al. IL-18 induces PD-1-dependent immunosuppression in cancer. Cancer Res. 2011;71(16):5393–9.

    Article  CAS  PubMed  Google Scholar 

  125. Yao J, Li ZH, Li YX, et al. Association between the −607 C > a polymorphism in interleukin-18 gene promoter with gastrointestinal cancer risk: a meta-analysis. Genet Mol Res. 2015;14(4):16880–7.

    Article  CAS  PubMed  Google Scholar 

  126. Tu S, Bhagat G, Cui G, et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 2008;14(5):408–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Chen J, Ye Y, Liu P, et al. Suppression of T cells by myeloid-derived suppressor cells in cancer. Hum Immunol. 2017;78(2):113–9.

    Article  CAS  PubMed  Google Scholar 

  128. Diaz-Montero CM, Salem ML, Nishimura MI, et al. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58(1):49–59.

    Article  CAS  PubMed  Google Scholar 

  129. Mantovani A. The growing diversity and spectrum of action of myeloid-derived suppressor cells. Eur J Immunol. 2010;40(12):3317–20.

    Article  CAS  PubMed  Google Scholar 

  130. Parker KH, Beury DW, Ostrand-Rosenberg S. Myeloid-derived suppressor cells: critical cells driving immune suppression in the tumor microenvironment. Adv Cancer Res. 2015;128:95–139.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Chang WJ, Du Y, Zhao X, et al. Inflammation-related factors predicting prognosis of gastric cancer. World J Gastroenterol. 2014;20(16):4586–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Shoji H, Tada K, Kitano S, et al. The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy. Oncotarget. 2017;8(56):95083–94.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Ricci V, Romano M, Boquet P. Molecular cross-talk between Helicobacter pylori and human gastric mucosa. World J Gastroenterol. 2011;17(11):1383–99.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Zhuang Y, Shi Y, Liu XF, et al. Helicobacter pylori infected macrophages induce Th17 cell differentiation. Immunobiology. 2011;216(1–2):200–7.

    Article  CAS  PubMed  Google Scholar 

  135. Ichiyama K, Yoshida H, Wakabayashi Y, et al. Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem. 2008;283(25):17003–8. https://doi.org/10.1074/jbc.M801286200. Epub 2008 Apr 23.

    Article  CAS  PubMed  Google Scholar 

  136. Caruso C, Lio D, Cavallone L, et al. Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci. 2004;1028:1–13.

    Article  CAS  PubMed  Google Scholar 

  137. Zanussi S, Serraino D, Dolcetti R, et al. Cancer, aging and immune reconstitution. Anti Cancer Agents Med Chem. 2013;13(9):1310–24.

    Article  CAS  Google Scholar 

  138. Serelli-Lee V, Ling KL, Ho C, et al. Persistent Helicobacter pylori specific Th17 responses in patients with past H. pylori infection are associated with elevated gastric mucosal IL-1beta. PLoS One. 2012;7(6):e39199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Akhiani AA, Pappo J, Kabok Z, et al. Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells. J Immunol. 2002;169(12):6977–84.

    Article  CAS  PubMed  Google Scholar 

  140. Jager A, Kuchroo VK. Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol. 2010;72(3):173–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Zhang Y, Zhang Y, Gu W, et al. TH1/TH2 cell differentiation and molecular signals. Adv Exp Med Biol. 2014;841:15–44.

    Article  CAS  PubMed  Google Scholar 

  142. Kabisch R, Semper RP, Wustner S, et al. Helicobacter pylori gamma-glutamyltranspeptidase induces tolerogenic human dendritic cells by activation of glutamate receptors. J Immunol. 2016;196(10):4246–52.

    Article  PubMed  CAS  Google Scholar 

  143. Bergman MP, Engering A, Smits HH, et al. Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med. 2004;200(8):979–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Larussa T, Leone I, Suraci E, et al. Enhanced expression of indoleamine 2, 3-dioxygenase in Helicobacter pylori-infected human gastric mucosa modulates Th1/Th2 pathway and interleukin 17 production. Helicobacter. 2015;20(1):41–8.

    Article  CAS  PubMed  Google Scholar 

  145. Pellicanò A, Imeneo M, Leone I, et al. Enhanced activation of Cyclooxygenase-2 downregulates Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa. Helicobacter. 2007;12(3):193–9.

    Article  PubMed  Google Scholar 

  146. Toller IM, Hitzler I, Sayi A, et al. Prostaglandin E2 prevents Helicobacter-induced gastric preneoplasia and facilitates persistent infection in a mouse model. Gastroenterology. 2010;138(4):1455–67.

    Article  CAS  PubMed  Google Scholar 

  147. Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defence. Br J Nutr. 2005;93(Suppl 1):S41–8.

    Article  CAS  PubMed  Google Scholar 

  148. Taylor JM, Ziman ME, Canfield DR, et al. Effects of a Th1-versus a Th2-biased immune response in protection against Helicobacter pylori challenge in mice. Microb Pathog. 2008;44(1):20–7.

    Article  CAS  PubMed  Google Scholar 

  149. Marotti B, Rocco A, De Colibus P, et al. Interleukin-13 mucosal production in Helicobacter pylori-related gastric diseases. Dig Liver Dis. 2008;40(4):240–7.

    Article  CAS  PubMed  Google Scholar 

  150. Yang P, Qiu G, Wang S, et al. The mutations of Th1 cell-specific T-box transcription factor may be associated with a predominant Th2 phenotype in gastric cancers. Int J Immunogenet. 2010;37(2):111–5.

    Article  CAS  PubMed  Google Scholar 

  151. Liu X, Cao K, Xu C, et al. GATA-3 augmentation down-regulates Connexin43 in Helicobacter Pylori associated gastric carcinogenesis. Cancer Biol Ther. 2015;16(6):987–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Sun X, Zhang M, El-Zataari M, et al. TLR2 mediates Helicobacter pylori-induced tolerogenic immune response in mice. PLoS One. 2013;8(9):e74595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Nemati M, Larussa T, Khorramdelazad H, et al. Toll-like receptor 2: an important immunomodulatory molecule during Helicobacter pylori infection. Life Sci. 2017;178:17–29.

    Article  CAS  PubMed  Google Scholar 

  154. Das S, Suarez G, Beswick EJ, et al. Expression of B7-H1 on gastric epithelial cells: its potential role in regulating T cells during Helicobacter pylori infection. J Immunol. 2006;176(5):3000–9.

    Article  CAS  PubMed  Google Scholar 

  155. Mitchell P, Afzali B, Fazekasova H, et al. Helicobacter pylori induces in-vivo expansion of human regulatory T cells through stimulating interleukin-1β production by dendritic cells. Clin Exp Immunol. 2012;70(3):300–9.

    Article  CAS  Google Scholar 

  156. Zhang C, Zhang X. ChenXH. Inhibition of the interleukin-6 signaling pathway: a strategy to induce immune tolerance. Clin. Rev. Allerg Immunol. 2014;47(2):163–73.

    CAS  Google Scholar 

  157. Zheng SG. Regulatory T cells vs Th17: differentiation of Th17 versus Treg, are they mutually exclusive? Afr J Clin Exp Immunol. 2013;2(1):94–106.

    Google Scholar 

  158. Hamajima N, Naito M, Kondo T, et al. Genetic factors involved in the development of Helicobacter pylori-related gastric cancer. Cancer Sci. 2006;97(11):1129–38.

    Article  CAS  PubMed  Google Scholar 

  159. Li M, Wang Y, Gu Y. Quantitative assessment of the influence of tumor necrosis factor alpha polymorphism with gastritis and gastric cancer risk. Tumour Biol. 2014;35(2):1495–502.

    Article  CAS  PubMed  Google Scholar 

  160. Loh M, Koh KX, Yeo BH, et al. Meta-analysis of genetic polymorphisms and gastric cancer risk: variability in associations according to race. Eur J Cancer. 2009;45(14):2562–8.

    Article  CAS  PubMed  Google Scholar 

  161. Silva-Fernandes IJ, da Silva TA, Agnez-Lima LF, et al. Helicobacter pylori genotype and polymorphisms in DNA repair enzymes: where do they correlate in gastric cancer? J Surg Oncol. 2012;106(4):448–55.

    Article  CAS  PubMed  Google Scholar 

  162. Goto Y, Ando T, Yamamoto K, et al. Association between serum pepsinogens and polymorphismof PTPN11 encoding SHP-2 among Helicobacter pylori seropositive Japanese. Int J Cancer. 2006;118(1):203–8.

    Article  CAS  PubMed  Google Scholar 

  163. Kawai S, Goto Y, Ito LS, et al. Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians. Gastric Cancer. 2006;9(4):277–83.

    Article  CAS  PubMed  Google Scholar 

  164. Hishida A, Matsuo K, Goto Y, et al. Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese. BMC Gastroenterol. 2009;9:51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. He C, Tu H, Sun L, et al. Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese. Carcinogenesis. 2013;34(7):1450–7.

    Article  CAS  PubMed  Google Scholar 

  166. Wang GY, Lu CQ, Zhang RM, et al. The E-cadherin gene polymorphism 160C->A and cancer risk: a HuGE review and meta-analysis of 26 case-control studies. Am J Epidemiol. 2008;167(1):7–14.

    Article  PubMed  Google Scholar 

  167. Gao L, Nieters A, Brenner H. Meta-analysis: tumour invasion-related genetic polymorphisms and gastric cancer susceptibility. Aliment Pharmacol Ther. 2008;28(5):565–73.

    Article  CAS  PubMed  Google Scholar 

  168. Wang Q, Gu D, Wang M, et al. The E-cadherin (CDH1) -160C>A polymorphism associated with gastric cancer among Asians but not Europeans. DNA Cell Biol. 2011;30(6):395–400.

    Article  CAS  PubMed  Google Scholar 

  169. Chen B, Zhou Y, Yang P, et al. CDH1 -160C>A gene polymorphism is an ethnicity-dependent risk factor for gastric cancer. Cytokine. 2011;55(2):266–73.

    Article  CAS  PubMed  Google Scholar 

  170. Cui Y, Xue H, Lin B, et al. A meta-analysis of CDH1 C-160A genetic polymorphism and gastric cancer risk. DNA Cell Biol. 2011;30(11):937–45.

    Article  CAS  PubMed  Google Scholar 

  171. Li YL, Tian Z, Zhang JB, et al. CDH1 promoter polymorphism and stomach cancer susceptibility. Mol Biol Rep. 2012;39(2):1283–6.

    Article  CAS  PubMed  Google Scholar 

  172. Wang L, Wang G, Lu C, et al. Contribution of the -160C/A polymorphism in the E-cadherin promoter to cancer risk: a meta-analysis of 47 case-control studies. PLoS One. 2012;7(7):e40219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. 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(2):420–7.

    Article  CAS  PubMed  Google Scholar 

  174. Fan H, Liu D, Qiu X, et al. A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma. BMC Med. 2010;8:12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Ravishankar Ram M, Goh KL, Leow AH, et al. Polymorphisms at locus 4p14 of toll-like receptors TLR-1 and TLR-10 confer susceptibility to gastric carcinoma in Helicobacter pylori infection. PLoS One. 2015;10(11):e0141865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Rigoli L, Di Bella C, Fedele F, et al. TLR4 and NOD2/CARD15 genetic polymorphisms and their possible role in gastric carcinogenesis. Anticancer Res. 2010;30(2):513–7.

    CAS  PubMed  Google Scholar 

  177. Hold GL, Rabkin CS, Chow WH, et al. A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors. Gastroenterology. 2007;132(3):905–12.

    Article  CAS  PubMed  Google Scholar 

  178. Santini D, Angeletti S, Ruzzo A, et al. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in gastric cancer of intestinal and diffuse histotypes. Clin Exp Immunol. 2008;154(3):360–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Jing JJ, Li M, Yuan Y. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis. Gene. 2012;499(2):237–42.

    Article  CAS  PubMed  Google Scholar 

  180. Hishida A, Matsuo K, Goto Y, et al. Toll-like receptor 4 +3725 G/C polymorphism, Helicobacter pylori seropositivity, and the risk of gastric atrophy and gastric cancer in Japanese. Helicobacter. 2009;14(1):47–53.

    Article  CAS  PubMed  Google Scholar 

  181. De Oliveira JG, Silva AE. Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population. World J Gastroenterol. 2012;18(11):1235–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Tahara T, Arisawa T, Wang F, et al. Toll-like receptor 2–196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer. Cancer Sci. 2007;98(11):1790–4.

    Article  CAS  PubMed  Google Scholar 

  183. Tahara T, Arisawa T, Wang F, et al. Toll-like receptor 2 (TLR) -196 to 174del polymorphism in gastro-duodenal diseases in Japanese population. Dig Dis Sci. 2008;53(4):919–24.

    Article  CAS  PubMed  Google Scholar 

  184. Zeng HM, Pan KF, Zhang Y, et al. Genetic variants of toll-like receptor 2 and 5, helicobacter pylori infection, and risk of gastric cancer and its precursors in a chinese population. Cancer Epidemiol Biomark Prev. 2011;20(12):2594–602.

    Article  CAS  Google Scholar 

  185. Hofner P, Gyulai Z, Kiss ZF, et al. Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis. Helicobacter. 2007;12(2):124–31.

    Article  CAS  PubMed  Google Scholar 

  186. Kara B, Akkiz H, Doran F, et al. The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis? Clin Exp Med. 2010;10(2):107–12.

    Article  CAS  PubMed  Google Scholar 

  187. Wang P, Zhang L, Jiang JM, et al. Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population. World J Gastroenterol. 2012;18(17):2112–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Kim EJ, Lee JR, Chung WC, et al. Association between genetic polymorphisms of NOD 1 and Helicobacter pylori-induced gastric mucosal inflammation in healthy Korean population. Helicobacter. 2013;18(2):143–50.

    Article  CAS  PubMed  Google Scholar 

  189. Li ZX, Wang YM, Tang FB, et al. NOD1 and NOD2 genetic variants in association with risk of gastric Cancer and its precursors in a Chinese population. PLoS One. 2015;10(5):e0124949.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Castaño-Rodríguez N, Kaakoush NO, Goh KL, et al. The NOD-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer: a case-control study and gene expression analyses. PLoS One. 2014;9(6):e98899.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  191. Companioni O, Bonet C, Muñoz X, et al. Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort. Int J Cancer. 2014;134(1):92–101.

    Article  PubMed  CAS  Google Scholar 

  192. Wex T, Ebert MP, Kropf S, et al. Gene polymorphisms of the NOD-2/CARD-15 gene and the risk of gastric cancer in Germany. Anticancer Res. 2008;28(2A):757–62.

    CAS  PubMed  Google Scholar 

  193. Hnatyszyn A, Szalata M, Stanczyk J, et al. Association of c.802C>T polymorphism of NOD2/CARD15 gene with the chronic gastritis and predisposition to cancer in H. pylori infected patients. Exp Mol Pathol. 2010;88(3):388–93.

    Article  CAS  PubMed  Google Scholar 

  194. Angeletti S, Galluzzo S, Santini D, et al. NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to gastric cancer in an Italian population. Hum Immunol. 2009;70(9):729–32.

    Article  CAS  PubMed  Google Scholar 

  195. Cooney R, Baker J, Brain O, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 2010;16(1):90–7.

    Article  CAS  PubMed  Google Scholar 

  196. Salucci V, Rimoldi M, Penati C, et al. Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria. Inflamm Bowel Dis. 2008;14(6):812–8.

    Article  PubMed  Google Scholar 

  197. Ying HY, Yu BW, Yang Z, et al. Interleukin-1B 31 C>T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies. J Cell Mol Med. 2016;20(3):526–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Park MJ, Hyun MH, Yang JP, et al. Effects of the interleukin-1β-511 C/T gene polymorphism on the risk of gastric cancer in the context of the relationship between race and H. pylori infection: a meta-analysis of 20,000 subjects. Mol Biol Rep. 2015;42(1):119–34.

    Article  CAS  PubMed  Google Scholar 

  199. Persson C, Canedo P, Machado JC, et al. Polymorphisms in inflammatory response genes and their association with gastric cancer: a HuGE systematic review and meta-analyses. Am J Epidemiol. 2011;173(3):259–70.

    Article  PubMed  Google Scholar 

  200. Lu W, Pan K, Zhang L, et al. Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population. Carcinogenesis. 2005;26(3):631–6.

    Article  CAS  PubMed  Google Scholar 

  201. Cheng D, Hao Y, Zhou W, et al. Positive association between Interleukin-8 -251A > T polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis. Cancer Cell Int. 2013;13(1):100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Wu MS, Wu CY, Chen CJ, et al. Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese. Int J Cancer. 2003;104(5):617–23.

    Article  CAS  PubMed  Google Scholar 

  203. Yang JP, Hyun MH, Yoon JM, et al. Association between TNF-α-308 G/A gene polymorphism and gastric cancer risk: a systematic review and meta-analysis. Cytokine. 2014;70(2):104–14.

    Article  CAS  PubMed  Google Scholar 

  204. Yu JY, Li L, Ma H, et al. Tumor necrosis factor-α 238 G/A polymorphism and gastric cancer risk: a meta-analysis. Tumour Biol. 2013;34(6):3859–63.

    Article  CAS  PubMed  Google Scholar 

  205. Qin Q, Lu J, Zhu H, et al. PARP-1 Val762Ala polymorphism and risk of cancer: a meta-analysis based on 39 case-control studies. PLoS One. 2014;9(5):e98022.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Zhang WH, Wang XL, Zhou J, et al. Association of interleukin-1B (IL-1B) gene polymorphisms with risk of gastric cancer in Chinese population. Cytokine. 2005;30(6):378–81.

    Article  CAS  PubMed  Google Scholar 

  207. Yang JJ, Cho LY, Ma SH, et al. Oncogenic CagA promotes gastric cancer risk via activating ERK signaling pathways: a nested case-control study. PLoS One. 2011;6(6):e21155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Yang JJ, Cho LY, Ko KP, et al. Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer. PLoS One. 2012;7(2):e31020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Arbour NC, Lorenz E, Schutte BC, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25(2):187–91.

    Article  CAS  PubMed  Google Scholar 

  210. Rallabhandi P, Bell J, Boukhvalova MS, et al. Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling. J Immunol. 2006;177(1):322–32.

    Article  CAS  PubMed  Google Scholar 

  211. Mommersteeg MC, Yu J, Peppelenbosch MP, et al. Genetic host factors in Helicobacter pylori-induced carcinogenesis: emerging new paradigms. Biochim Biophys Acta. 2018;1869(1):42–52.

    CAS  Google Scholar 

  212. Camargo MC, Mera R, Correa P, et al. Interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis. Cancer Epidemiol Biomark Prev. 2006;15:1674–87.

    Article  CAS  Google Scholar 

  213. Kamangar F, Cheng C, Abnet CC, et al. Interleukin-1B polymorphisms and gastric cancer risk—a meta-analysis. Cancer Epidemiol Biomark Prev. 2006;15:1920–8.

    Article  CAS  Google Scholar 

  214. Camargo MC, Mera R, Correa P, et al. IL1B polymorphisms and gastric cancer risk. Cancer Epidemiol Biomark Prev. 2007;16(3):635; author reply 635–6.

    Article  CAS  Google Scholar 

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  1. Immunopathology and Cancer Biomarkers, IRCCS, CRO Aviano, National Cancer Institute, Aviano, PN, Italy

    Stefania Zanussi, Mariateresa Casarotto & Chiara Pratesi

  2. IRCCS, CRO Aviano, National Cancer Institute, Aviano, PN, Italy

    Paolo De Paoli

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    Vincenzo Canzonieri

  2. Sbarro Institute for Cancer, Research and Molecular Medicine, Department of Biology, Temple University, Philadelphia, PA, USA

    Antonio Giordano

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Zanussi, S., Casarotto, M., Pratesi, C., Paoli, P.D. (2019). Gastric Tumorigenesis: Role of Inflammation and Helicobacter pylori. In: Canzonieri, V., Giordano, A. (eds) Gastric Cancer In The Precision Medicine Era. Current Clinical Pathology. Humana, Cham. https://doi.org/10.1007/978-3-030-04861-7_1

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