Abstract
Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been well described. Individual susceptibility to GC development depends on the host’s genetic predisposition, H. pylori virulence factors, environmental conditions, and geographical determinants. Biological determinants are urgently sought to predict the clinical course of infection in individuals with confirmed H. pylori infection. Possible candidates for such biomarkers include genetic aberrations such as single-nucleotide polymorphisms (SNPs) found in various cytokines/growth factors (e.g., IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17A/B, IFN-γ, TNF, TGF-β) and their receptors (IL-RN, TGFR), innate immunity receptors (TLR2, TLR4, CD14, NOD1, NOD2), enzymes involved in signal transduction cascades (PLCE1, PKLR, PRKAA1) as well as glycoproteins (MUC1, PSCA), and DNA repair enzymes (ERCC2, XRCC1, XRCC3). Bacterial determinants related to GC development include infection with CagA-positive (particularly with a high number of EPIYA-C phosphorylation motifs) and VacA-positive isolates (in particular s1/m1 allele strains). The combined genotyping of bacterial and host determinants suggests that the accumulation of polymorphisms favoring host and bacterial features increases the risk for precancerous and cancerous lesions in patients.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Abdi E, Latifi-Navid S, Zahri S, Yazdanbod A, Safaralizadeh R (2017) Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: A very high-risk area in Northwestern Iran. Microb Pathog 107:287–292. https://doi.org/10.1016/j.micpath.2017.04.007
Al-Sammak F, Kalinski T, Weinert S, Link A, Wex T, Malfertheiner P (2013) Gastric epithelial expression of IL-12 cytokine family in Helicobacter pylori infection in humans: is it head or tail of the coin? PLoS One 17 8(9):e75192. https://doi.org/10.1371/journal.pone.0075192
Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE (2014) Effect of Helicobacter pylori on gastric epithelial cells. World J Gastroenterol 20:12767–12780. https://doi.org/10.3748/wjg.v20.i36.12767
Arisawa T, Tahara T, Shiroeda H, Matsue Y, Minato T, Nomura T, Yamada H, Hayashi R, Saito T, Matsunaga K, Fukuyama T, Hayashi N, Otsuka T, Fukumura A, Nakamura M, Shibata T (2012) Genetic polymorphisms of IL17A and pri-microRNA-938, targeting IL17A3’-UTR, influence susceptibility to gastric cancer. Human Immunol 73:747–752. https://doi.org/10.1016/j.humimm.2012.04.011
Aspholm M, Olfat F, Nordén J, Sondén B, Lundberg C, Sjöström R, Altraja S, Odenbreit S, Haas R, Wadström T, Engstrand L, Semino-Mora C, Liu H, Dubois A, Teneberg S, Arnqvist A, Borén T (2006) SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans. PLoS Pathog 2(10):e110. https://doi.org/10.1371/journal.ppat.0020110
Backert S, Naumann M (2010) What a disorder: proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol 18(11):479–486. https://doi.org/10.1016/j.tim.2010.08.003
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.2007.10.006
Backert S, Tegtmeyer N, Selbach M (2010) The versatility of Helicobacter pylori CagA effector protein functions: the master key hypothesis. Helicobacter 15(3):163–176. https://doi.org/10.1111/j.1523-5378.2010.00759.x
Backert S, Tegtmeyer N, Fischer W (2015) Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system. Future Microbiol 10:955–965. https://doi.org/10.2217/fmb.15.32
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_8
Bagheri N, Azadegan-Dehkordi F, Sanei H, Taghikhani A, Rahimian G, Salimzadeh L, Hashemzadeh-Chaleshtori M, Rafieian-kopaei M, Shirzad M, Shirzad H (2014) Association of TLR4 single-nucleotide polymorphism with H. pylori associated gastric diseases in Iranian patients. Clin Res Hepatol Gastroenterol 38:366–371. https://doi.org/10.1016/j.clinre.2013.12.004
Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545. https://doi.org/10.1016/S0140-6736(00)04046-0
Barden S, Lange S, Tegtmeyer N, Conradi J, Sewald N, Backert S, Niemann HH (2013) A helical RGD motif promoting cell adhesion: crystal structures of the Helicobacter pylori type IV secretion system pilus protein CagL. Structure 21(11):1931–1941. https://doi.org/10.1016/j.str.2013.08.018
Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, Schiavon S, Guariso G, Ceroti M, Nitti D, Rugge M, Plebani M, Atherton JC (2008) Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 135(1):91–99. https://doi.org/10.1053/j.gastro.2008.03.041
Batista SA, Rocha GA, Rocha AM, Saraiva IE, Cabral MM, Oliveira RC, Queiroz DM (2011) Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol 11:61. https://doi.org/10.1186/1471-2180-11-61
Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE (2014) Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 94:329–354. https://doi.org/10.1152/physrev.00040.2012
Bockerstett KA, DiPaolo RJ (2017) Regulation of gastric carcinogenesis by inflammatory cytokines. Cell Mol Gastroenterol Hepatol 4:47–53. https://doi.org/10.1016/j.jcmgh.2017.03.005
Brenner D, Blaser H, Mak TW (2015) Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol 15:362–374. https://doi.org/10.1038/nri3834
Bridge DR, Merrell DS (2013) Polymorphism in the Helicobacter pylori CagA and VacA toxins and disease. Gut Microbes 4:101–117. https://doi.org/10.4161/gmic.23797
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):95–103
Butcher LD, den Hartog G, Ernst PB, Crowe SE (2017) Oxidative stress resulting from Helicobacter pylori infection contributes to gastric carcinogenesis. Cell Mol Gastroenterol Hepatol 3:316–322. https://doi.org/10.1016/j.jcmgh.2017.02.002
Buzzeli JN, Chalinor HV, Pavlic DI, Sutton P, Menheniott TR, Giraud AS, Judd LM (2015) IL-33 is a stomach alarmin that initiates a skewed Th2 response to injury and infection. Cell Mol Gastroenterol Hepatol 1:203–221. https://doi.org/10.1016/j.jcmgh.2014.12.003
Caleman Neto A, Rasmussen LT, de Labio RW, de Queiroz VF, Smith Mde A, Viani GA, Payão SL (2014) Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori. J Venom Anim Toxins Incl Trop Dis 20:17. https://doi.org/10.1186/1678-9199-20-17
Canedo P, Castanheira-Vale AJ, Lunet N, Pereira F, Figueiredo C, Gioia-Patricola L, Canzian F, Moreira H, Suriano G, Barros H, Carneiro F, Seruca R, Machado JC (2008) The interleukin-8-251*T/*A polymorphism is not associated with risk for gastric carcinoma development in a Portuguese population. Eur J Cancer Prev 17(1):28–32
Capellá G, Pera G, Sala N, Agudo A, Rico F, Del Giudicce G, Plebani M, Palli D, Boeing H, Bueno-de-Mesquita HB, Carneiro F, Berrino F, Vineis P, Tumino R, Panico S, Berglund G, Simán H, Nyrén O, Hallmans G, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quirós JR, Allen N, Key T, Bingham S, Caldas C, Linseisen J, Nagel G, Overvad K, Tjonneland A, Boshuizen HC, Peeters PH, Numans ME, Clavel-Chapelon F, Trichopoulou A, Lund E, Jenab M, Kaaks R, Riboli E, González CA (2008) DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study. Int J Epidemiol 37(6):1316–1325. https://doi.org/10.1093/ije/dyn145
Castaño-Rodríguez N, Kaakoush NO, Goh KL, Fock KM, Mitchell HM (2013) The role of TLR2, TLR4 and CD14 genetic polymorphisms in gastric carcinogenesis: a case-control study and meta analysis. PLoS ONE 8:e60327. https://doi.org/10.1371/journal.pone.0060327
Castaño-Rodríguez N, Kaakoush NO, Mitchell HM (2014) Pattern-recognition receptors and gastric cancer. Front Immunol 5:336. https://doi.org/10.3389/fimmu.2014.00336
Chen S, Zhu XC, Liu YL, Wang C, Zhang KG (2016a) Investigating the association between XRCC1 gene polymorphisms and susceptibility to gastric cancer. Genet Mol Res. 15(3). https://doi.org/10.4238/gmr.15038342
Chen YL, Mo XQ, Huang GR, Huang YQ, Xiao J, Zhao LJ, Wei HY (2016b) Gene polymorphisms of pathogenic Helicobacter pylori in patients with different types of gastrointestinal disease. World J Gastroenterol 22(44):9718–9726. https://doi.org/10.3748/wjg.v22.i44.9718
Cheng J, Fan XM (2013) Role of cyclooxygenase-2 in gastric cancer development and progression. World J Gastroenterol 19:7361–7368. https://doi.org/10.3748/wjg.v19.i42.7361
Cherati MR, Shokri-Shirvani J, Karkhah A, Rajabnia R, Nouri HR (2017) Helicobacter pylori cagL amino acid polymorphism D58E59 pave the way toward peptic ulcer disease while N58E59 is associated with gastric cancer in north of Iran. Microb Pathog 107:413–418. https://doi.org/10.1016/j.micpath.2017.04.025
Chmiela M, Miszczyk K, Rudnicka K (2014) Structural modifications of Helicobacter pylori lipopolysaccharide: an idea how to live in peace. World J Gastroenterol 20:9882–9897. https://doi.org/10.3748/wjg.v20.i29.9882
Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M (1975) A model for gastric cancer epidemiology. Lancet 2:58–60
Demitrack ES, Samuelson LC (2017) Notch as a driver of gastric epithelial cell proliferation. Cell Mol Gastroenterol Hepatol 3:323–330. https://doi.org/10.1016/j.jcmgh.2017.01.012
Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AH, Reindl W, Backert S, Saur D, Schmid RM, Rad R (2006) Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis 194:1346–1355. https://doi.org/10.1086/508426
El-Omar EM (2001) The importance of interleukin 1β in Helicobacter pylori associated disease. Gut 48:743–747
El-Omar EM, Oien K, El-Nujumi A, Gillen D, Wirz A, Dahill S, Williams C, Ardill JE, McColl KE (1997) Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 113:15–24. https://doi.org/10.1016/S0016-5085(97)70075-1
El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404(6776):398–402. https://doi.org/10.1038/35006081
Epplein M, Xiang YB, Cai Q, Peek RM Jr, Li H, Correa P, Gao J, Wu J, Michel A, Pawlita M, Zheng W, Shu XO (2013) Circulating cytokines and gastric cancer risk. Cancer Causes Control 24:2245–2250. https://doi.org/10.1007/s10552-013-0284-z
Ferreira RM, Machado JC, Leite M, Carneiro F, Figueiredo C (2012) The number of Helicobacter pylori CagA EPIYA C tyrosine phosphorylation motifs influences the pattern of gastritis and the development of gastric carcinoma. Histopathology 60:992–998. https://doi.org/10.1111/j.1365-2559.2012.04190.x
Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simões M (2002) Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94(22):1680–1687
Franco AT, Friedman DB, Nagy TA, Romero-Gallo J, Krishna U, Kendall A, Israel DA, Tegtmeyer N, Washington MK, Peek RM Jr (2009) Delineation of a carcinogenic Helicobacter pylori proteome. Mol Cell Proteomics 8:1947–1958. https://doi.org/10.1074/mcp.M900139-MCP200
Fukui H, Zhang X, Sun C, Hara K, Kikuchi S, Yamasaki T, Kondo T, Tomita T, Oshima T, Watari J, Imura J, Fujimori T, Sasako M, Miwa H (2014) IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signalling. Br J Cancer 111:763–771. https://doi.org/10.1038/bjc.2014.336
Garza-González E, Bosques-Padilla FJ, El-Omar E, Hold G, Tijerina-Menchaca R, Maldonado-Garza HJ, Pérez-Pérez GI (2005) Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. Int J Cancer 114(2):237–241. https://doi.org/10.1002/ijc.20718
Gifford GB, Demitrack ES, Keeley TM, Tam A, La Cunza N, Dedhia PH, Spence JR, Simeone DM, Saotome I, Louvi A, Siebel CW, Samuelson LC (2017) Notch 1 and Notch 2 receptors regulate mouse and human gastric antral epithelial cell homeostasis. Gut 66:1001–1011. https://doi.org/10.1136/gutjnl-2015-310811
González CA, Figueiredo C, Lic CB, Ferreira RM, Pardo ML, Ruiz Liso JM, Alonso P, Sala N, Capella G, Sanz-Anquela JM (2011) 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 106(5):867–874. https://doi.org/10.1038/ajg.2011.1
Goodwin AC, Weinberger DM, Ford CB, Nelson JC, Snider JD, Hall JD, Paules CI, Peek RM Jr, Forsyth MH (2008) Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system. Microbiology 154:2231–2240. https://doi.org/10.1099/mic.0.2007/016055-0
Grebowska A, Moran AP, Matusiak A, Bak-Romaniszyn L, Czkwianianc E, Rechciński T, Walencka M, Płaneta-Małecka I, Rudnicka W, Chmiela M (2008) Anti-phagocytic activity of Helicobacter pylori lipopolysaccharide (LPS)-possible modulation of the innate immune response to these bacteria. Pol J Microbiol 57:185–192
Grebowska A, Moran AP, Bielanski W, Matusiak A, Rechcinski T, Rudnicka K, Baranowska A, Rudnicka W, Chmiela M (2010) Helicobacter pylori lipopolysaccharide activity in human peripheral blood mononuclear leukocyte cultures. J Physiol Pharmacol 61:437–442
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.2015.08.074
Hayakawa Y, Fox JG, Wang TC (2017) Isthmus stem cells are the origins of metaplasia in the gastric corpus. Cell Mol Gastroenterol Hepatol 4:89–94. https://doi.org/10.1016/j.jcmgh.2017.02.009
Howlett M, Chalinor HV, Buzzelli JN, Nguyen N, van Driel IR, Bell KM, Fox JG, Dimitriadis E, Menheniott TR, Giraud AS, Judd LM (2012) IL-11 is a parietal cell cytokine that induces atrophic gastritis. Gut 61:1398–1409. https://doi.org/10.1136/gutjnl-2011-300539
Huang ZG, Tang GC (2010) Influence of Helicobacter pylori cagA gene of gastric mucosa epithelialcell tumor associated protein expression. Zhongguo Gonggongweishen Zazhi 26:881–883
Huang JQ, Zheng GF, Sumanac K, Irvine EJ, Hunt RH (2003) Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 125:1636–1644
Hunt RH, Camilleri M, Crowe SE, El-Omar EM, Fox JG, Kuipers EJ, Malfertheiner P, McColl KE, Pritchard DM, Rugge M, Sonnenberg A, Sugano K, Tack J (2015) The stomach in health and disease. Gut 64:1650–1668. https://doi.org/10.1136/gutjnl-2014-307595
Hwang IR, Kodama T, Kikuchi S, Sakai K, Peterson LE, Graham DY, Yamaoka Y (2002) Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection. Gastroenterology 123(6):1793–1803. https://doi.org/10.1053/gast.2002.37043
IARC Working Group on the Evaluation of Carcinogenic Risks to humans (1994) Schistosomes, liver flukes and Helicobacter pylori. IIARC Monogr Eval Carcinog Risks Hum 61:1–241
Islami F, Kamangar F (2008) Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res (Phila) 1(5):329–338. https://doi.org/10.1158/1940-6207.capr-08-0109
Jenks PJ, Jeremy AH, Robinson PA, Walker MM, Crabtree JE (2003) Long term infection with Helicobacter felis and inactivation of the tumor suppressor gene p53 cumulatively enhance the gastrin mutation frequency in Big Blue® transgenic mice. J Pathol 201:596–602. https://doi.org/10.1002/path.1488
Jiang YX, Li GM, Yi D, Yu PW (2015) A meta-analysis: The association between interleukin-17 pathway gene polymorphism and gastrointestinal diseases. Gene 572:243–251. https://doi.org/10.1016/j.gene.2015.07.018
Jones KR, Jang S, Chang JY, Kim J, Chung IS, Olsen CH, Merrell DS, Cha JH (2011) Polymorphisms in the intermediate region of VacA impact Helicobacter-pylori-induced disease development. J Clin Microbiol 49:101–110. https://doi.org/10.1128/JCM.01782-10
Kamada T, Kurose H, Yamanaka Y, Manabe N, Kusunoki H, Shiotani A, Inoue K, Hata J, Matsumoto H, Akiyama T, Hirai T, Sadahira Y, Haruma K (2012) Relationship between gastroesophageal junction adenocarcinoma and Helicobacter pylori infection in Japan. Digestion 85(4):256–260. https://doi.org/10.1159/000336352
Kamangar F, Abnet CC, Hutchinson AA, Newschaffer CJ, Helzlsouer K, Shugart YY, Pietinen P, Dawsey SM, Albanes D, Virtamo J, Taylor PR (2006) Polymorphisms in inflammation-related genes and risk of gastric cancer (Finland). Cancer Causes Control 17(1):117–125
Kawai M, Furuta Y, Yahara K, Tsuru T, Oshima K, Handa N, Takahashi N, Yoshida M, Azuma T, Hattori M, Uchiyama I, Kobayashi I (2011) Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes. BCM Microbiol 11:104. https://doi.org/10.1186/1471-2180-11-104
Khamri W, Walker MM, Clark P, Atherton JC, Thursz MR, Bamford KB, Lechler RI, Lombardi G (2010) Helicobacter pylori stimulates dendritic cells to induce interleukin-17 expression from CD4+ T lymphocytes. Infect Immun 78:845–853. https://doi.org/10.1128/IAI.00524-09
Kim J, Cho YA, Choi IJ, Lee YS, Kim SY, Shin A, Cho SJ, Kook MC, Nam JH, Ryu KW, Lee JH, Kim YW (2012) Effects of Interleukin-10 polymorphisms, Helicobacter pylori infection, and smoking on the risk of noncardia gastric cancer. PLoS ONE 7:e29643. https://doi.org/10.1371/journal.pone.0029643
Kim SG, Jung HK, Lee HL, Jang JY, Lee H, Kim CG, Shin WG, Shin ES, Lee YC (2013) Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Korean J Gastroenterol 62:3–26. https://doi.org/10.4166/kjg.2013.62.1.3
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 11:1703–1713. https://doi.org/10.1016/j.celrep.2015.05.030
Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, Konig W, Backert S (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449(7164):862–866. https://doi.org/10.1038/nature06187
Latifi-Navid S, Mohammadi S, Maleki P, Zahri S, Yazdanbod A, Siavoshi F, Massarrat S (2013) Helicobacter pylori vacA d1/-il genotypes and geographic differentiation between high and low incidence areas of gastric cancer in Iran. Arch Iran Med 16:330–337. doi:013166/AIM.005
Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS, Graham DY (2016) Association between Helicobacter pylori eradication and gastric cancer incidence: a systemic review and meta-analysis. Gastroenterology 150:1113–1124. https://doi.org/10.1053/j.gastro.2016.01.028
Li WQ, Zhang L, Ma JL, Zhang Y, Li JY, Pan KF, You WC (2009) Association between genetic polymorphisms of DNA base excision repair genes and evolution of precancerous gastric lesions in a Chinese population. Carcinogenesis 30(3):500–505. https://doi.org/10.1093/carcin/bgp018
Li Y, Dai L, Zhang J, Wang P, Chai Y, Ye H, Zhang J, Wang K (2012) Cyclooxygenase-2 polymorphisms and the risk of gastric cancer in various degrees of relationship in the Chinese Han population. Oncol Lett 3:107–112. https://doi.org/10.3892/ol.2011.426
Li ZX, Wang YM, Tang FB, Zhang L, Zhang, Ma JL, Zhou T, You WC, Pan KF (2015) NOD1 and NOD2 genetic variants in association with risk of gastric cancer and its precursors in a Chinese population. PLoS One 1 10(5):e0124949. https://doi.org/10.1371/journal.pone.0124949
Lind J, Backert S, Pfleiderer K, Berg DE, Yamaoka Y, Sticht H, Tegtmeyer N (2014) Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains. PLoS ONE 9(5):e96488. https://doi.org/10.1371/journal.pone.0096488
Lind J, Backert S, Hoffmann R, Eichler J, Yamaoka Y, Perez-Perez GI, Torres J, Sticht H, Tegtmeyer N (2016) Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of East Asian-type Helicobacter pylori strains. BMC Microbiol 16(1):201. https://doi.org/10.1186/s12866-016-0820-6
Liu J, Xu Q, Yuan Q, Wang Z, Xing C, Yuan Y (2015) Association of IL-17A and IL-17F polymorphisms with gastric cancer risk in Asians: a meta-analysis. Human Immunl 76:6–12. https://doi.org/10.1016/j.humimm.2014.12.011
Ma J, Wu D, Hu X, Li J, Cao M, Dong W (2017) Associations between cytokine gene polymorphisms and susceptibility to Helicobacter pylori infection and Helicobacter pylori related gastric cancer, peptic ulcer disease: A meta-analysis. PLoS ONE 4:e0176463. https://doi.org/10.1371/journal.pone.0176463
Machado JC, Pharoah P, Sousa S, Carvalho R, Oliveira C, Figueiredo C, Amorim A, Seruca R, Caldas C, Carneiro F, Sobrinho-Simões M (2001) Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology 121(4):823–829
Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, Castro Alves C, Campos ML, Van Doorn LJ, Caldas C, Seruca R, Carneiro F, Sobrinho-Simões M (2003) A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125(2):364–371. https://doi.org/10.1016/S0016-5085(03)00899-0
Machado AM, Figueiredo C, Touati E, Máximo V, Sousa S, Michel V, Carneiro F, Nielsen FC, Seruca R, Rasmussen LJ (2009) Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells. Clin Cancer Res 15:2995–3002. https://doi.org/10.1158/1078-0432.CCR-08-2686
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.2013.08.004
Malaty HM, El-Kasabany A, Graham DY, Miller CC, Reddy SG, Srinivasan SR, Yamaoka Y, Berenson GS (2002) Age at acquisition of Helicobacter pylori infection: a follow up study from infancy to adulthood. Lancet 359:931–988. https://doi.org/10.1016/S0140-6736(02)08025-X
Matos JI, de Sousa HA, Marcos-Pinto R, Dinis-Ribeiro M (2013) Helicobacter pylori CagA and VacA genotypes and gastric phenotype: a meta-analysis. Eur J Gastroenterol Hepatol 25(12):1431–1441. https://doi.org/10.1097/MEG.0b013e328364b53e
McClain MS, Beckett AC, Cover TL (2017) Helicobacter pylori vacuolating toxin and gastric cancer. Toxins 9(10):E316. https://doi.org/10.3390/toxins9100316
McLean MH, El-Omar EM (2014) Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 11:664–674. https://doi.org/10.1038/nrgastro.2014.143
Meira LB, Bugni JM, Green SL, Lee CW, Pang B, Borenshtein D, Rickman BH, Rogers AB, Moroski-Erkul CA, McFaline JL, Schauer DB, Dedon PC, Fox JG, Samson LD (2008) DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest 118:2516–2525. https://doi.org/10.1172/JCI35073
Melchiades JL, Zabaglia LM, Sallas ML, Orcini WA, Chen E, Smith MAC, Payão SLM, Rasmussen LT (2017) Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori. Cytokine 96:203–207. https://doi.org/10.1016/j.cyto.2017.04.020
Melo Barbosa HP, Martins LC, Dos Santos SE, Demachki S, Assumpção MB, Aragão CD, de Oliveira Corvelo TC (2009) Interleukin-1 and TNF-alpha polymorphisms and Helicobacter pylori in a Brazilian Amazon population. World J Gastroenterol 15:1465–1471
Memon AA, Hussein NR, Miendje Deyi VY, Burette A, Atherton JC (2014) Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: a matched case-control study. AJ Clin Microbiol. 52(8):2984–2989. https://doi.org/10.1128/JCM.00551-14
Mizuno T, Ando T, Nobata K, Tsuzuki T, Maeda O, Watanabe O, Minami M, Ina K, Kusugami K, Peek RM, Goto H (2005) Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization. World J Gastroenterol 11:6305–6311
Mnich E, Gajewski A, Rudnicka K, Gonciarz W, Stawerski P, Hinc K, Obuchowski M, Chmiela M (2015) Immunoregulation of antigen presenting and secretory functions of monocytic cells by Helicobacter pylori antigens in relation to impairment of lymphocyte expansion. Acta Biochim Pol 62:641–650. https://doi.org/10.18388/abp.2015_1045
Mocellin S, Verdi D, Pooley KA, Nitti D (2015) Genetic variation and gastric cancer risk: a field synopsis and meta-analysis. Gut 64(8):1209–1219. https://doi.org/10.1136/gutjnl-2015-309168
Moss SF (2016) The clinical evidence linking Helicobacter pylori to gastric cancer. Cell Mol Gastroenterol Hepatol 3(2):183–191. https://doi.org/10.1016/j.jcmgh.2016.12.001
Mukherjee T, Hovingh ES, Foerster EG, Abdel-Nour M, Philpott DJ, Girardin SE (2018) NOD1 and NOD2 in inflammation, immunity and disease. Arch Biochem Biophys pii S0003–9861(18):30937–30938. https://doi.org/10.1016/j.abb.2018.12.022
Naumann M, Sokolova O, Tegtmeyer N, Backert S (2017) Helicobacter pylori: a paradigm pathogen for subverting host cell signal transmission. Trends Microbiol 25:316–328. https://doi.org/10.1016/j.tim.2016.12.004
Ng MT, Van’t Hof R, Crockett JC, Hope ME, Berry S, Thomson J, McLean MH, McColl KE, El-Omar EM, Hold GL (2010) Increase in NF-kappaB binding affinity of the variant C allele of the toll-like receptor 9–1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease. Infect Immun 78(3):1345–1352. https://doi.org/10.1128/IAI.01226-09
Ni P, Xu H, Xue H, Lin B, Lu Y (2012) A Meta-analysis on Interleukin-10-1082 promoter polymorphism associated with gastric cancer risk. DNA and Cell Biol 31:582–590. https://doi.org/10.1089/dna.2011.1440
Nogueira C, Figueiredo C, Carneiro F, Gomes AT, Barreira R, Figueira P, Salgado C, Belo L, Peixoto A, Bravo JC, Bravo LE, Realpe JL, Plaisier AP, Quint WG, Ruiz B, Correa P, van Doorn LJ (2001) Helicobacter pylori genotypes may determine gastric histopathology. Am J Pathol 158(2):647–654
Ogiwara H, Sugimoto M, Ohno T, Vilaichone RK, Mahachai V, Graham DY, Yamaoka Y (2009) Role of deletion located between the intermediate and middle regions of the Helicobacter pylori vacA gene in cases gastroduodenal diseases. J Clin Microbiol 47:3493–3500. https://doi.org/10.1128/JCM.00887-09
Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, Koike T, Sekine H, Ohara S, Shimosegawa T (2005) The polymorphism interleukin 8–251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut 54:330–335. https://doi.org/10.1136/gut.2003.033050
Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C, Vauterin M, Suerbaum S, Achtman M, Linz B (2010) A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PloS Genet 6:e1001069. https://doi.org/10.1371/journal.pgen.1001069
Oleastro M, Ménard A (2013) The role of Helicobacter pylori outer membrane proteins in adherence and pathogenesis. Biology (Basel) 2:1110–1134. https://doi.org/10.3390/biology2031110
Pachathundikandi SK, Lind J, Tegtmeyer N, El-Omar EM, Backert S (2015) Interplay of the Gastric Pathogen Helicobacter pylori with Toll-Like Receptors. Biomed Res Int 2015:192420. https://doi.org/10.1155/2015/192420
Palomo J, Dietrich D, Martin P, Palmer G, Gabay C (2015) The interleukin (IL)-1 cytokine family–Balance between agonists and antagonists in inflammatory diseases. Cytokine 76(1):25–37. https://doi.org/10.1016/j.cyto.2015.06.017
Paziak-Domanska B, Chmiela M, Jarosińska A, Rudnicka W (2000) Potential role of CagA in the inhibition of T cell reactivity in Helicobacter pylori infections. Cell Immunol 202:136–139. https://doi.org/10.1006/cimm.2000.1654
Peleteiro B, Lunet N, Carrilho C, Durães C, Machado JC, La Vecchia C, Barros H (2010) Association between cytokine gene polymorphisms and gastric precancerous lesions: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 19(3):762–776. https://doi.org/10.1158/1055-9965.EPI-09-0917
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/kwq370
Petersen CP, Meyer AR, De Salvo C, Choi E, Schlegel C, Petersen A, Engevik AC, Prasad N, Levy SE, Peebles RS, Pizarro TT, Goldenring JR (2018) A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach. Gut 67:805–817. https://doi.org/10.1136/gutjnl-2016-312779
Pimentel-Nunes P, Afonso L, Lopes P, Roncon-Albuquerque R Jr, Gonçalves N, Henrique R, Moreira-Dias L, Leite-Moreira AF, Dinis-Ribeiro M (2011) Increased expression of toll-like receptors (TLR) 2, 4, 5 in gastric dysplasia. Pathol Oncol Res 17:677–683. https://doi.org/10.1007/s12253-011-9368-9
Plummer M, van Doorn LJ, Franceschi S, Kleter B, Canzian F, Vivas J, Lopez G, Colin D, Muñoz N, Kato I (2007) Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. J Natl Cancer Inst 99:1328–1334. https://doi.org/10.1093/jnci/djm120
Plummer M, Franceschi S, Vignat J, Forman D, de Martel C (2015) Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer 136:487–490. https://doi.org/10.1002/ijc.28999
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
Qinghai Z, Yanying W, Yunfang C, Xukui Z, Xiaoqiao Z (2014) Effect of interleukin-17A and interleukin-17F gene polymorphisms on the risk of gastric cancer in Chinese population. Gene 537:328–332. https://doi.org/10.1016/j.gene.2013.11.007
Quin XP, Zhou Y, Chen Y, Li NN, Wu XT (2014) XRCC3 Thr241Met polymorphism and gastric cancer susceptibility: a meta-analysis. Clin Res Hepatol Gastroenterol 38:226–234. https://doi.org/10.1016/j.clinre.2013.10.011
Rad R, Prinz C, Neu B, Neuhofer M, Zeitner M, Voland P, Becker I, Schepp W, Gerhard M (2003) Synergistic effect of Helicobacter pylori virulence factors and interleukin-1 polymorphisms for the development of severe histological changes in the gastric mucosa. J Infect Dis 188(2):272–281. https://doi.org/10.1086/376458
Ramis IB, Vianna JS, Gonçalves CV, von Groll A, Dellagostin OA, da Silva PEA (2015) Polymorphisms of the IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori. J Microbiol Immunol Infect 50:153–159. https://doi.org/10.1016/j.jmii.2015.03.002
Rhead JL, Letley DP, Mohammadi M, Hussein N, Mohagheghi MA, Eshagh Hosseini M, Atherton JC (2007) A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology 133(3):926–936. https://doi.org/10.1053/j.gastro.2007.06.056
Rosenstiel P, Hellmig S, Hampe J, Ott S, Till A, Fischbach W, Sahly H, Lucius R, Fölsch UR, Philpott D, Schreiber S (2006) Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. Cell Microbiol 8(7):1188–1198
Rudnicka K, Miszczyk E, Matusiak A, Walencka M, Moran AP, Rudnicka W, Chmiela M (2015) Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity. Innate Immun 21:127–139. https://doi.org/10.1177/1753425913518225
Savage SA, Hou L, Lissowska J, Chow WH, Zatonski W, Chanock SJ, Yeager M (2006) Interleukin-8 polymorphisms are not associated with gastric cancer risk in a Polish population. Cancer Epidemiol Biomarkers Prev 15(3):589–591
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 107:15217–15222. https://doi.org/10.1073/pnas.1009017107
Shibata J, Goto H, Arisawa T, Niwa Y, Hayakawa T, Nakayama A, Mori N (1999) Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection. Gut 45:24–31
Shigematsu Y, Niwa T, Rehnberg E, Toyoda T, Yoshida S, Mori A, Wakabayashi M, Iwakura Y, Ichinose M, Kim YJ, Ushijima T (2013) Interleukin-1beta induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis. Cancer Lett 340(1):141–147. https://doi.org/10.1016/j.canlet.2013.07.034
Sicinschi LA, Lopez-Carrillo L, Camargo MC, Correa P, Sierra RA, Henry RR, Chen J, Zabaleta J, Piazuelo MB, Schneider BG (2006) Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and -10 genes. Int J Cancer 118(3):649–657. https://doi.org/10.1002/ijc.21364
Sicinschi LA, Correa P, Peek RM, Camargo MC, Piazuelo MB, Romero-Gallo J, Hobbs SS, Krishna U, Delgado A, Mera R, Bravo LE, Schneider BG (2010) CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect 2010:369–378. https://doi.org/10.1111/j.1469-0691.2009.02811.x
Smith SM (2014) Role of Toll-like receptors in Helicobacter pylori infection and immunity. World J Gastrointest Pathophysiol 5(3):133–146. https://doi.org/10.4291/wjgp.v5.i3.133
Sun X, Xu Y, Wang L, Zhang F, Zhang J, Fu X, Jing T, Han J (2016) Association between TNF A gene polymorphisms and Helicobacter pylori infection: a meta-analysis. PLoS ONE 54:703–706. https://doi.org/10.1371/journal.pone.0147410
Tanaka S, Nagashima H, Cruz M, Uchida T, Uotani T, Jiménez Abreu JA, Mahachai V, Vilaichone RK, Ratanachu-Ek T, Tshering L, Graham DY, Yamaoka Y (2017) Interleukin 17C in human Helicobacter pylori gastritis. InfectImmun 85:e00389–17. https://doi.org/10.1128/IAI.00389-17
The EUROGAST Study Group (1993) An international association between Helicobacter pylori infection and gastric cancer. Lancet 341:1359–1362
Torres LE, Melián K, Moreno A, Alonso J, Sabatier CA, Hernández M, Bermúdez L, Rodríguez BL (2009) Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World J Gastroenterol 15:204–210
Tsai CY, Wang CS, Tsai MM, Chi HC, Cheng WL, Tseng YH, Chen CY, Lin CD, Wu JI, Wang LH, Lin KH (2014) Interleukin-32 increases human gastric cancer cell invasion associated with tumor progression and metastasis. Clin Cancer Res 20:2276–2288. https://doi.org/10.1158/1078-0432.CCR-13-1221
Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X (2017) Prevention of gastric cancer: eradication of Helicobacter pylori and beyond. Int J Mol Sci 18:1699. https://doi.org/10.3390/ijms18081699
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.2008.10.011
Varga MG, Peek RM (2017) DNA Transfer and Toll-like receptor modulation by Helicobacter pylori. Curr Top Microbiol Immunol 400:169–193. https://doi.org/10.1007/978-3-319-50520-6_8
Vaziri F, Peerayeh SN, Alebouyeh M, Maghsoudi N, Azimzadeh P, Siadat SD, Zali MR (2015) Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study. Pathog Dis 73(3):ftu021. https://doi.org/10.1093/femspd/ftu021
Wang P, Zhang L, Jiang JM, Ma D, Tao HX, Yuan SL, Wang YC, Wang LC, Liang H, Zhang ZS, Liu CJ (2012) Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer risk in Chinese population. Worl J Gastroenterol 18:2112–2120. https://doi.org/10.3748/wjg.v18.i17.2112
Wang J, Guo X, Yu S, Song J, Zhang J, Cao Z, Wang J, Liu M, Dong W (2014) Association between CD14 gene polymorphisms and cancer risk: a meta analysis. PLoS ONE 9(6):e100122. https://doi.org/10.1371/journal.pone.0100122
Warren JR, Marshall BJ (1983) Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1:1273–1275
Winter JA, Letley DP, Cook KW, Rhead JL, Zaitoun AA, Ingram RJ, Amilon KR, Croxall NJ, Kaye PV, Robinson K, Atherton JC (2014) A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach. J Infect Dis 210(6):954–963. https://doi.org/10.1093/infdis/jiu154
Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK, Chen JS, China Gastric Cancer Study Group (2004) Helicobacter pylori eradication to prevent gastric cancer in a high risk region of China: a randomized controlled trial. JAMA 291:187–194. https://doi.org/10.1001/jama.291.2.187
Wu MS, Wu CY, Chen CJ, Lin MT, Shun CT, Lin JT (2003) Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese. Int J Cancer 104(5):617–623. https://doi.org/10.1002/ijc.10987
Wu WK, Lee CW, Cho CH, Fan D, Wu K, Yu J, Sung JJ (2010) MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene 29:5761–5771. https://doi.org/10.1038/onc.2010.352
Wu HH, Lin WC, Tsai KW (2013) Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Rev Mol Med 16:e1. https://doi.org/10.1017/erm.2013.16
Xu Y, Cao X, Jiang J, Chen Y, Wang K (2017) TNF-α-308/-238 polymorphisms are associated with gastric cancer: a case-control family study in China. Clin Res Hepatol Gastroenterol 41(1):103–109. https://doi.org/10.1016/j.clinre.2016.05.014
Yamaoka Y (2008) Roles of Helicobacter pylori BabA in gastroduodenal pathogenesis. World J Gastroenterol 14:4265–4272
Ye F, Brauer T, Niehus E, Drlica K, Josenhans C, Suerbaum S (2007) Flagellar and global gene regulation in Helicobacter pylori modulated by changes in DNA supercoiling. Int J Med Microbiol 297:65–81. https://doi.org/10.1016/j.ijmm.2006.11.006
Ying HY, Yu BW, Yang Z, Yang SS, Bo LH, Shan XY, Wang HJ, Zhu YJ, Wu XS (2016) Interleukin-1B 31 C > T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies. J Cell Mol Med 20:526–536. https://doi.org/10.1111/jcmm.12737
Zambon CF, Navaglia F, Basso D, Rugge M, Plebani M (2003) Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia. J Clin Pathol 56:287–291
Zambon CF, Basso D, Navaglia F, Belluco C, Falda A, Fogar P, Greco E, Gallo N, Rugge M, Di Mario F, Plebani M (2005) Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome. Cytokine 29:141–152. https://doi.org/10.1016/j.cyto.2004.10.013
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
Zhang JZ, Liu CM, Peng HP, Zhang Y (2017) Association of genetic variations in IL-6/IL6R pathway genes with gastric cancer risk in a Chinese population. Gene 623:1–4. https://doi.org/10.1016/j.gene.2017.04.038
Zhao F, Zhu H, Huang M, Yi C, Huang Y (2014) The 765 G > C polymorphism in the cyclooxygenase-2 gene and gastric cancer risk: an update by meta-analysis. Asian Pac J Cancer Prev 15:2863–2868
Zhou Q, Wang C, Wang X, Wu X, Zhu Z, Liu B, Su L (2014) Association between TLR4 (+896A/G and +1196C/T) polymorphisms and gastric cancer risk: an updated meta-analysis. PLoS ONE 9:e109605. https://doi.org/10.1371/journal.pone.0109605
Acknowledgements
The preparation of the chapter was financed by the National Science Center grant SONATA no. 2016/23/D/NZ6/02553. The work of SB was supported by the German Science Foundation (project A04 in CRC-1181).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Rudnicka, K., Backert, S., Chmiela, M. (2019). Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences. In: Backert, S. (eds) Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori. Current Topics in Microbiology and Immunology, vol 421. Springer, Cham. https://doi.org/10.1007/978-3-030-15138-6_3
Download citation
DOI: https://doi.org/10.1007/978-3-030-15138-6_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-15137-9
Online ISBN: 978-3-030-15138-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)