Abstract
Gastric cancer is widespread and remains a leading cause of cancer-related death worldwide. Infection with Helicobacter pylori is one of the strongest known risk factors for this malignancy. There is a high level of genetic diversity among H. pylori strains, and bacterial virulence factors play an important role in determining the risk of developing gastric adenocarcinoma following colonization with H. pylori. Infection with strains that contain a cag pathogenicity island or type s1 vacA alleles confers increased risk compared to infection with other strain types. Additional risk factors for gastric cancer include dietary factors, such as a high-salt diet and iron deficiency. H. pylori can interact with stem cell populations and in this way may promote gastric carcinogenesis. Recent studies suggest that components of the microbiome may also influence H. pylori-induced carcinogenesis. In this review article, we discuss mechanisms by which H. pylori infection can lead to gastric cancer.
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References
Aberg A, Gideonsson P, Vallstrom A, Olofsson A, Ohman C, Rakhimova L, Boren T, Engstrand L, Brannstrom K, Arnqvist A (2014) A repetitive DNA element regulates expression of the Helicobacter pylori sialic acid binding adhesin by a rheostat-like mechanism. PLoS Pathog 10:e1004234, http://www.ncbi.nlm.nih.gov/pubmed/24991812
Argent RH, Hale JL, El-Omar EM, Atherton JC (2008) Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and east Asian strains, and influences on interleukin-8 secretion. J Med Microbiol 57:1062–1067, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18719174
Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270:17771–17777, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7629077
Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ (1997) Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 112:92–99, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8978347
Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M et al (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36, http://www.ncbi.nlm.nih.gov/pubmed/20085740
Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, Schiavon S, Guariso G, Ceroti M, Nitti D et al (2008) Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 135:91–99, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18474244
Beevers DG, Lip GY, Blann AD (2004) Salt intake and Helicobacter pylori infection. J Hypertens 22:1475–1477, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15257168
Blaser MJ, Berg DE (2001) Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest 107:767–773, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11285290
Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr (1991) Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265:1287–1289, http://www.ncbi.nlm.nih.gov/pubmed/1995976
Boquet P, Ricci V (2012) Intoxication strategy of Helicobacter pylori VacA toxin. Trends Microbiol 20:165–174, http://www.ncbi.nlm.nih.gov/pubmed/22364673
Cabarcas SM, Mathews LA, Farrar WL (2011) The cancer stem cell niche – there goes the neighborhood? Int J Cancer J Int Cancer 129:2315–2327, http://www.ncbi.nlm.nih.gov/pubmed/21792897
Correa P (1992) Human gastric carcinogenesis: a multistep and multifactorial process – first American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res 52:6735–6740, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1458460
Correa P (1996) Helicobacter pylori and gastric cancer: state of the art. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the Am Soc Prev Oncol 5:477–481 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8781746
Correa P (2004) Is gastric cancer preventable? Gut 53:1217–1219, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15306570
Correa P, Houghton J (2007) Carcinogenesis of Helicobacter pylori. Gastroenterology 133:659–672, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17681184
Correa P, Cuello C, Duque E, Burbano LC, Garcia FT, Bolanos O, Brown C, Haenszel W (1976) Gastric cancer in Colombia. III. Natural history of precursor lesions. J Natl Cancer Inst 57:1027–1035, http://www.ncbi.nlm.nih.gov/pubmed/1003539
Cover TL, Blanke SR (2005) Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol 3:320–332, http://www.ncbi.nlm.nih.gov/pubmed/15759043
de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, Plummer M (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13:607–615, http://www.ncbi.nlm.nih.gov/pubmed/22575588
de Vries AC, van Grieken NC, Looman CW, Casparie MK, de Vries E, Meijer GA, Kuipers EJ (2008) Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology 134:945–952, http://www.ncbi.nlm.nih.gov/pubmed/18395075
DuBois S, Kearney DJ (2005) Iron-deficiency anemia and Helicobacter pylori infection: a review of the evidence. Am J Gastroenterol 100:453–459, http://www.ncbi.nlm.nih.gov/pubmed/15667507
Epplein M, Nomura AM, Hankin JH, Blaser MJ, Perez-Perez G, Stemmermann GN, Wilkens LR, Kolonel LN (2008) Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case-control study in Hawaii. Cancer Causes Control: CCC 19:869–877, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18369531
Everhart JE (2000) Recent developments in the epidemiology of Helicobacter pylori. Gastroenterol Clin North Am 29:559–578, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11030073
Falk PG, Bry L, Holgersson J, Gordon JI (1995) Expression of a human alpha-1,3/4-fucosyltransferase in the pit cell lineage of FVB/N mouse stomach results in production of Leb-containing glycoconjugates: a potential transgenic mouse model for studying Helicobacter pylori infection. Proc Natl Acad Sci U S A 92:1515–1519, http://www.ncbi.nlm.nih.gov/pubmed/7878011
Fischer W, Puls J, Buhrdorf R, Gebert B, Odenbreit S, Haas R (2001) Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol 42:1337–1348, http://www.ncbi.nlm.nih.gov/pubmed/11886563
Forman D, Pisani P (2008) Gastric cancer in Japan – honing treatment, seeking causes. N Engl J Med 359:448–451, http://www.ncbi.nlm.nih.gov/pubmed/18669423
Fox JG, Wang TC (2007) Inflammation, atrophy, and gastric cancer. J Clin Invest 117:60–69, http://www.ncbi.nlm.nih.gov/pubmed/17200707
Franco AT, Johnston E, Krishna U, Yamaoka Y, Israel DA, Nagy TA, Wroblewski LE, Piazuelo MB, Correa P, Peek RM Jr (2008) Regulation of gastric carcinogenesis by Helicobacter pylori virulence factors. Cancer Res 68:379–387, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18199531
Fuchs CS, Mayer RJ (1995) Gastric carcinoma. N Engl J Med 333:32–41, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7776992
Gaddy JA, Radin JN, Loh JT, Zhang F, Washington MK, Peek RM Jr, Algood HM, Cover TL (2013) High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. Infect Immun 81:2258–2267, http://www.ncbi.nlm.nih.gov/pubmed/23569116
Gamboa-Dominguez A, Ubbelohde T, Saqui-Salces M, Romano-Mazzoti L, Cervantes M, Dominguez-Fonseca C, de la Luz Estreber M, Ruiz-Palacios GM (2007) Salt and stress synergize H. pylori-induced gastric lesions, cell proliferation, and p21 expression in Mongolian gerbils. Dig Dis Sci 52:1517–1526, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17404882
Gancz H, Jones KR, Merrell DS (2008) Sodium chloride affects Helicobacter pylori growth and gene expression. J Bacteriol 190:4100–4105, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18375562
Ge Z, Feng Y, Muthupalani S, Eurell LL, Taylor NS, Whary MT, Fox JG (2011) Coinfection with Enterohepatic Helicobacter species can ameliorate or promote Helicobacter pylori-induced gastric pathology in C57BL/6 mice. Infect Immun 79:3861–3871, http://www.ncbi.nlm.nih.gov/pubmed/21788386
Gerhard M, Lehn N, Neumayer N, Boren T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C (1999) Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci U S A 96:12778–12783, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10535999
Gonzalez CA, Jakszyn P, Pera G, Agudo A, Bingham S, Palli D, Ferrari P, Boeing H, del Giudice G, Plebani M et al (2006) Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 98:345–354, http://www.ncbi.nlm.nih.gov/pubmed/16507831
Gonzalez CA, Lujan-Barroso L, Bueno-de-Mesquita HB, Jenab M, Duell EJ, Agudo A, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Touillaud M et al (2012) Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up. Int J Cancer J Int Cancer 131:2910–2919, http://www.ncbi.nlm.nih.gov/pubmed/22473701
Guruge JL, Falk PG, Lorenz RG, Dans M, Wirth HP, Blaser MJ, Berg DE, Gordon JI (1998) Epithelial attachment alters the outcome of Helicobacter pylori infection. Proc Natl Acad Sci U S A 95:3925–3930, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9520469
Haile RW, John EM, Levine AJ, Cortessis VK, Unger JB, Gonzales M, Ziv E, Thompson P, Spruijt-Metz D, Tucker KL et al (2012) A review of cancer in U.S. Hispanic populations. Cancer Prev Res 5:150–163, http://www.ncbi.nlm.nih.gov/pubmed/22307564
Hatakeyama M (2004) Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 4:688–694, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15343275
Helicobacter, and Cancer Collaborative, G (2001) Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 49:347–353, http://www.ncbi.nlm.nih.gov/pubmed/11511555
Hennig EE, Mernaugh R, Edl J, Cao P, Cover TL (2004) Heterogeneity among Helicobacter pylori strains in expression of the outer membrane protein BabA. Infect Immun 72:3429–3435, http://www.ncbi.nlm.nih.gov/pubmed/15155649
Higashi H, Yokoyama K, Fujii Y, Ren S, Yuasa H, Saadat I, Murata-Kamiya N, Azuma T, Hatakeyama M (2005) EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. J Biol Chem 280:23130–23137, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15831497
Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC (2004) Gastric cancer originating from bone marrow-derived cells. Science 306:1568–1571, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15567866
Howson CP, Hiyama T, Wynder EL (1986) The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev 8:1–27, http://www.ncbi.nlm.nih.gov/pubmed/3533579
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, http://www.ncbi.nlm.nih.gov/pubmed/14724815
Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Boren T (1998) Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279:373–377, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9430586
Kato S, Tsukamoto T, Mizoshita T, Tanaka H, Kumagai T, Ota H, Katsuyama T, Asaka M, Tatematsu M (2006) High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylori-infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells. Int J Cancer J Int Cancer 119:1558–1566, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16646055
Kim MK, Sasaki S, Sasazuki S, Tsugane S, Japan Public Health Center-based Prospective Study, G (2004) Prospective study of three major dietary patterns and risk of gastric cancer in Japan. Int J Cancer J Int Cancer 110:435–442, http://www.ncbi.nlm.nih.gov/pubmed/15095311
Kim HJ, Lim SY, Lee JS, Park S, Shin A, Choi BY, Shimazu T, Inoue M, Tsugane S, Kim J (2010) Fresh and pickled vegetable consumption and gastric cancer in Japanese and Korean populations: a meta-analysis of observational studies. Cancer Sci 101:508–516, http://www.ncbi.nlm.nih.gov/pubmed/19860848
Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, Konig W et al (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449:862–866, http://www.ncbi.nlm.nih.gov/pubmed/17943123
Lee SA, Kang D, Shim KN, Choe JW, Hong WS, Choi H (2003) Effect of diet and Helicobacter pylori infection to the risk of early gastric cancer. J Epidemiol 13:162–168, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12749604
Lee CW, Rickman B, Rogers AB, Muthupalani S, Takaishi S, Yang P, Wang TC, Fox JG (2009) Combination of sulindac and antimicrobial eradication of Helicobacter pylori prevents progression of gastric cancer in hypergastrinemic INS-GAS mice. Cancer Res 69:8166–8174, http://www.ncbi.nlm.nih.gov/pubmed/19826057
Lemke LB, Ge Z, Whary MT, Feng Y, Rogers AB, Muthupalani S, Fox JG (2009) Concurrent Helicobacter bilis infection in C57BL/6 mice attenuates proinflammatory H. pylori-induced gastric pathology. Infect Immun 77:2147–2158, http://www.ncbi.nlm.nih.gov/pubmed/19223483
Lertpiriyapong K, Whary MT, Muthupalani S, Lofgren JL, Gamazon ER, Feng Y, Ge Z, Wang TC, Fox JG (2014) Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in the Helicobacter pylori INS-GAS mouse model of gastric carcinogenesis. Gut 63:54–63, http://www.ncbi.nlm.nih.gov/pubmed/23812323
Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, Falush D, Stamer C, Prugnolle F, van der Merwe SW et al (2007) An African origin for the intimate association between humans and Helicobacter pylori. Nature 445:915–918, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17287725
Lofgren JL, Whary MT, Ge Z, Muthupalani S, Taylor NS, Mobley M, Potter A, Varro A, Eibach D, Suerbaum S et al (2011) Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology 140:210–220, http://www.ncbi.nlm.nih.gov/pubmed/20950613
Loh JT, Torres VJ, Cover TL (2007) Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res 67:4709–4715, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17510398
Loh JT, Friedman DB, Piazuelo MB, Bravo LE, Wilson KT, Peek RM Jr, Correa P, Cover TL (2012) Analysis of Helicobacter pylori cagA promoter elements required for salt-induced upregulation of CagA expression. Infect Immun 80:3094–3106, http://www.ncbi.nlm.nih.gov/pubmed/22710874
Mahdavi J, Sonden B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA et al (2002) Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297:573–578, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12142529
Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311–1315, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6145023
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. J Clin Microbiol 52:2984–2989, http://www.ncbi.nlm.nih.gov/pubmed/24920772
Miehlke S, Kirsch C, Agha-Amiri K, Günther T, Lehn N, Malfertheiner P, Stolte M, Ehninger G, Bayerdörffer E (2000) The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric carcinoma in Germany. Int J Cancer 87(3):322–327. PMID: 10897035
Naito M, Yamazaki T, Tsutsumi R, Higashi H, Onoe K, Yamazaki S, Azuma T, Hatakeyama M (2006) Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA. Gastroenterology 130:1181–1190, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16618412
Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ (1991) Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325:1132–1136, http://www.ncbi.nlm.nih.gov/pubmed/1891021
Noto JM, Khizanishvili T, Chaturvedi R, Piazuelo MB, Romero-Gallo J, Delgado AG, Khurana SS, Sierra JC, Krishna US, Suarez G et al (2013) Helicobacter pylori promotes the expression of Kruppel-like factor 5, a mediator of carcinogenesis, in vitro and in vivo. PLoS One 8:e54344, http://www.ncbi.nlm.nih.gov/pubmed/23372710
Odenbreit S, Puls J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287:1497–1500, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10688800
Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M et al (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci U S A 105:1003–1008, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18192401
Oliveira AG, Santos A, Guerra JB, Rocha GA, Rocha AM, Oliveira CA, Cabral MM, Nogueira AM, Queiroz DM (2003) babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. J Clin Microbiol 41:3964–3966, http://www.ncbi.nlm.nih.gov/pubmed/12904430
Park JM, Park SH, Hong KS, Han YM, Jang SH, Kim EH, Hahm KB (2014) Special licorice extracts containing lowered glycyrrhizin and enhanced licochalcone a prevented Helicobacter pylori-initiated, salt diet-promoted gastric tumorigenesis. Helicobacter 19:221–236, http://www.ncbi.nlm.nih.gov/pubmed/24646026
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15761078
Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131, http://www.ncbi.nlm.nih.gov/pubmed/1891020
Parsonnet J, Friedman GD, Orentreich N, Vogelman H (1997) Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 40:297–301, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9135515
Peek RM Jr, Crabtree JE (2006) Helicobacter infection and gastric neoplasia. J Pathol 208:233–248, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16362989
Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR (1993) Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 104:510–513, http://www.ncbi.nlm.nih.gov/pubmed/8425693
Plummer M, Franceschi S, Vignat J, Forman D, de Martel C (2014) Global burden of gastric cancer attributable to pylori. Int J Cancer J Int Cancer 136:487–490, http://www.ncbi.nlm.nih.gov/pubmed/24889903
Polk DB, Peek RM Jr (2010) Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10:403–414, http://www.ncbi.nlm.nih.gov/pubmed/20495574
Powell AE, Wang Y, Li Y, Poulin EJ, Means AL, Washington MK, Higginbotham JN, Juchheim A, Prasad N, Levy SE et al (2012) The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149:146–158, http://www.ncbi.nlm.nih.gov/pubmed/22464327
Ren JS, Kamangar F, Forman D, Islami F (2012) Pickled food and risk of gastric cancer – a systematic review and meta-analysis of English and Chinese literature. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the Am Soc Prev Oncol 21:905–915 http://www.ncbi.nlm.nih.gov/pubmed/22499775
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 133:926–936, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17854597
Shaffer CL, Gaddy JA, Loh JT, Johnson EM, Hill S, Hennig EE, McClain MS, McDonald WH, Cover TL (2011) Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface. PLoS Pathog 7:e1002237, http://www.ncbi.nlm.nih.gov/pubmed/21909278
Sheh A, Fox JG (2013) The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis. Gut Microbes 4:505–531, http://www.ncbi.nlm.nih.gov/pubmed/23962822
Shikata K, Kiyohara Y, Kubo M, Yonemoto K, Ninomiya T, Shirota T, Tanizaki Y, Doi Y, Tanaka K, Oishi Y et al (2006) A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study. Int J Cancer J Int Cancer 119:196–201, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16450397
Sipponen P, Marshall BJ (2000) Gastritis and gastric cancer. Western countries. Gastroenterol Clin North Am 29:579–592, v-vi http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11030074
Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D, Bray F (2012) Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet 380:1840–1850, http://www.ncbi.nlm.nih.gov/pubmed/23079588
Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M (2004) Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci U S A 101:2106–2111, http://www.ncbi.nlm.nih.gov/pubmed/14762173
Song H, Michel A, Nyren O, Ekstrom AM, Pawlita M, Ye W (2014) A CagA-independent cluster of antigens related to the risk of noncardia gastric cancer: associations between Helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology. Int J Cancer J Int Cancer 134:2942–2950, http://www.ncbi.nlm.nih.gov/pubmed/24259284
Styer CM, Hansen LM, Cooke CL, Gundersen AM, Choi SS, Berg DE, Benghezal M, Marshall BJ, Peek RM Jr, Boren T et al (2010) Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun 78:1593–1600, http://www.ncbi.nlm.nih.gov/pubmed/20123715
Sun J, Aoki K, Zheng JX, Su BZ, Ouyang XH, Misumi J (2006) Effect of NaCl and Helicobacter pylori vacuolating cytotoxin on cytokine expression and viability. World J Gastroenterol 12:2174–2180, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16610017
Syder AJ, Guruge JL, Li Q, Hu Y, Oleksiewicz CM, Lorenz RG, Karam SM, Falk PG, Gordon JI (1999) Helicobacter pylori attaches to NeuAc alpha 2,3Gal beta 1,4 glycoconjugates produced in the stomach of transgenic mice lacking parietal cells. Mol Cell 3:263–274, http://www.ncbi.nlm.nih.gov/pubmed/10198629
Syder AJ, Oh JD, Guruge JL, O’Donnell D, Karlsson M, Mills JC, Bjorkholm BM, Gordon JI (2003) The impact of parietal cells on Helicobacter pylori tropism and host pathology: an analysis using gnotobiotic normal and transgenic mice. Proc Natl Acad Sci U S A 100:3467–3472, http://www.ncbi.nlm.nih.gov/pubmed/12629225
Thomson MJ, Pritchard DM, Boxall SA, Abuderman AA, Williams JM, Varro A, Crabtree JE (2012) Gastric Helicobacter infection induces iron deficiency in the INS-GAS mouse. PLoS One 7:e50194, http://www.ncbi.nlm.nih.gov/pubmed/23185574
Tsugane S (2005) Salt, salted food intake, and risk of gastric cancer: epidemiologic evidence. Cancer Sci 96:1–6, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15649247
Tsugane S, Sasazuki S (2007) Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer: Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc 10:75–83, http://www.ncbi.nlm.nih.gov/pubmed/17577615
Uehara T, Ma D, Yao Y, Lynch JP, Morales K, Ziober A, Feldman M, Ota H, Sepulveda AR (2013) H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer. Dig Dis Sci 58:140–149, http://www.ncbi.nlm.nih.gov/pubmed/22945475
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784–789, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11556297
Varon C, Dubus P, Mazurier F, Asencio C, Chambonnier L, Ferrand J, Giese A, Senant-Dugot N, Carlotti M, Megraud F (2012) Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice. Gastroenterology 142:281–291, http://www.ncbi.nlm.nih.gov/pubmed/22062361
Wang J, Fan X, Lindholm C, Bennett M, O’Connoll J, Shanahan F, Brooks EG, Reyes VE, Ernst PB (2000a) Helicobacter pylori modulates lymphoepithelial cell interactions leading to epithelial cell damage through Fas/Fas ligand interactions. Infect Immun 68:4303–4311, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10858249
Wang TC, Dangler CA, Chen D, Goldenring JR, Koh T, Raychowdhury R, Coffey RJ, Ito S, Varro A, Dockray GJ et al (2000b) Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology 118:36–47, http://www.ncbi.nlm.nih.gov/pubmed/10611152
Whary MT, Muthupalani S, Ge Z, Feng Y, Lofgren J, Shi HN, Taylor NS, Correa P, Versalovic J, Wang TC et al (2014) Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota. Microbes Infect/Institut Pasteur 16:345–355, http://www.ncbi.nlm.nih.gov/pubmed/24513446
Winter JA, Letley DP, Cook KW, Rhead JL, Zaitoun AA, Ingram RJ, Amilon KR, Croxall NJ, Kaye PV, Robinson K et al (2014) A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach. J Infect Dis 210:954–963, http://www.ncbi.nlm.nih.gov/pubmed/24625807
Wu X, Chen VW, Andrews PA, Ruiz B, Correa P (2007) Incidence of esophageal and gastric cancers among Hispanics, non-Hispanic whites and non-Hispanic blacks in the United States: subsite and histology differences. Cancer Causes Control: CCC 18:585–593, http://www.ncbi.nlm.nih.gov/pubmed/17406989
Yamaoka Y, Ojo O, Fujimoto S, Odenbreit S, Haas R, Gutierrez O, El-Zimaity HM, Reddy R, Arnqvist A, Graham DY (2006) Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 55:775–781, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16322107
Yip R, Limburg PJ, Ahlquist DA, Carpenter HA, O’Neill A, Kruse D, Stitham S, Gold BD, Gunter EW, Looker AC et al (1997) Pervasive occult gastrointestinal bleeding in an Alaska native population with prevalent iron deficiency. Role of Helicobacter pylori gastritis. JAMA 277:1135–1139, http://www.ncbi.nlm.nih.gov/pubmed/9087468
Yu J, Leung WK, Go MY, Chan MC, To KF, Ng EK, Chan FK, Ling TK, Chung SC, Sung JJ (2002) Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant gastric lesions. Gut 51:480–484, http://www.ncbi.nlm.nih.gov/pubmed/12235067
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Peek, R.M., Wroblewski, L.E. (2016). Helicobacter pylori Infection and Gastric Cancer. In: Backert, S., Yamaoka, Y. (eds) Helicobacter pylori Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55936-8_17
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