Helicobacter Pylori and Gastric Precancerous Lesions: An update
Abstract
Gastric cancer (GC) develops through a multistep process known as the gastritis-atrophy-metaplasia-dysplasia-cancer sequence associated with alterations in the expression of host oncogenes and tumor suppressor genes after several decades. Helicobacter pylori (H. pylori) infection is the most consistent risk factor for GC, and its elimination is, therefore, the most promising strategy to reduce the incidence of this malignant disorder. However, the results of the relevant studies are controversial as to whether the H. Pylori eradication effectively induces the regression of gastric preneoplastic lesions. The inconsistencies are likely due to the heterogeneity in studies with respect to the number of biopsy samples taken, the method of histologic classification of findings, sample size, and the duration of the follow-up. Additionally some probable or well-defined factors other than H. Pylori may influence the progression of gastric preneoplastic lesions. Lastly, the real existence of a “point of no return” may partially explain the controversial findings. Here, we present an index case, and review data about the role of H. pylori during gastric carcinogenesis, and subsequently discuss information available from recent studies to evaluate the benefit of the H. pylori eradication for the regression of gastric precancerous lesions.
References
Ernst PB, Peura DA, Crowe SE. The Translation of Helicobacter pylori Basic Research to Patient Care. Gastroenterology 2006; 130: 188-206.
Kivi M, Johansson AL, Reilly M, Tindberg Y. Helicobacter pylori status in family members as risk factors for infection in children. Epidemiol Infect 2005; 133: 645-52.
Epplein M, Nomura AM, Hankin JH, Blaser MJ, Perez-Perez G, Stemmermann GN, et al. Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case–control study in Hawaii. Cancer Causes Control 2008; 19: 869-77.
Rugge M, Capelle LG, Cappellesso R, Nitti D, Kuipers EJ. Precancerous lesions in the stomach: From biology to clinical patient management. Best Pract Res Clin Gastroenterol 2013; 27: 205-23.
Bin L, Meng L. Helicobacter pylori eradication for preventing gastric cancer. World J Gastroenterol 2014; 20: 5660-5.
Pan KF, Formichella L, Zhang L, Zhang Y, Ma JL, Li ZX, et al. Helicobacter pylori antibody responses and evolution of precancerous gastric lesions in a Chinese population. Int J Cancer 2014; 134: 2118-25.
Faribourz MG, Farahnaz J, Yaghoub R, Tolou H. Screening of Precancerous Gastric Lesions by Serum Pepsinogen, Gastrin-17, Anti-Helicobacter Pylori and Anti- Caga Antibodies in Dyspeptic Patients over 50 years Old in Guilan Province, North of Iran. APJCP 2014; 15: 7635-8.
Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. Gut 2012; 61: 646-64.
Moayyedi P, Soo S, Deeks J, Delaney B, Harris A, Innes M, Oakes R, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev 2003; 2: CD002096.
Bytzer P, Dahlerup JF, Eriksen JR, Jarbøl DE, Rosenstock S, Wildt S; Danish Society for Gastroenterology. Diagnosis and treatment of Helicobacter pylori infection. Dan Med Bull 2011; 58: C4271.
Chey WD, Wong BC; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007; 102: 180825.
Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 2010; 23: 713-39.
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345: 784-9.
Kikuchi S. Epidemiology of Helicobacter pylori and gastric cancer. Gastric Cancer 2002; 5: 6-15.
Sepulveda AR, Graham DY. Role of Helicobacter pylori in gastric carcinogenesis. Gastroenterol Clin North Am 2002; 31: 517-35.
Brenner H, Arndt V, Stegmaier C, Ziegler H, Rothenbacher D. Is Helicobacter pylori infection a necessary condition for noncardia gastric cancer? Am J Epidemiol 2004; 159: 252-8.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process-First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992; 52: 6735-40.
Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology. 2007; 133: 659-72.
Hatakeyama M. Helicobacter pylori and gastric carcinogenesis. J Gastroenterol 2009; 44: 239-48.
Yoshida T, Kato J, Inoue I, Yoshimura N, Deguchi H, Mukoubayashi C, et al. Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer. Int J Cancer 2014; 134: 1445-7.
Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology 2009; 136: 1863-73.
Nardone G, Rocco A, Malfertheiner P. Review article: helicobacter pylori and molecular events in precancerous gastric lesions. Aliment Pharmacol Ther 2004; 20: 261-70.
Correa P. Does Helicobacter pylori cause gastric cancer via oxidative stress? Biol Chem 2006; 387: 361-4.
Watanabe M, Kato J, Inoue I, Yoshimura N, Yoshida T, Mukoubayashi C, et al. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis. Int J Cancer 2012; 131: 2632-42.
Huang JQ, Zheng GF, Sumanac K, Irvine EJ, Hunt RH. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003; 125: 1636-44.
Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 2002; 295: 683-6.
Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA 2002; 99: 14428–33.
Higashi H, Yokoyama K, Fujii Y, Ren S, Yuasa H, Saadat I, et al. EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. J Biol Chem 2005; 280: 23130-7.
Naito M, Yamazaki T, Tsutsumi R, Higashi H, Onoe K, Yamazaki S, et al. Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA. Gastroenterology 2006; 130: 1181-90.
Higashi H, Nakaya A, Tsutsumi R, Yokoyama K, Fujii Y, Ishikawa S, et al. Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. J Biol Chem 2004; 279: 17205–16.
Higuchi M, Tsutsumi R, Higashi H, Hatakeyama M. Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity. Cancer Sci 2004; 95: 442-7.
Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 2003; 34: 148-50.
Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, et al. Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res 2004; 64: 8816-20.
Goto Y, Ando T, Yamamoto K, Tamakoshi A, El-Omar E, Goto H, et al. Association between serum pepsinogens and polymorphismof PTPN11 encoding SHP-2 among Helicobacter pylori seropositive Japanese. Int J Cancer 2006; 118: 203-8.
Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 2003; 300: 1430-4.
Saadat I, Higashi H, Obuse C, Umeda M, Murata-Kamiya N, Saito Y, et al. Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature 2007; 447: 330-3.
Zeaiter Z, Cohen D, Musch A, Bagnoli F, Covacci A, Stein M. Analysis of detergent-resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity. Cell Microbiol 2008; 10: 781-94.
Toback FG, Walsh-Reitz MM, Musch MW, Chang EB, Del Valle J, Ren H, et al. Peptide fragments of AMP-18, a novel secreted gastric antrum mucosal protein, are mitogenic and motogenic. Am J Physiol Gastrointest Liver Physiol 2003; 285: 344-53.
Nardone G, Rippa E, Martin G, Rocco A, Siciliano RA, Fiengo A, et al. Gastrokine 1 expression in patients with and without Helicobacter pylori infection. Dig Liver Dis 2007; 39: 122-9.
Shiozaki K, Nakamori S, Tsujie M, Okami J, Yamamoto H, Nagano H, et al. Human stomach-specific gene, CA11, is down-regulated in gastric cancer. Int J Oncol 2001; 19: 701-7.
Yoon JH, Seo HS, Choi SS, Chae HS, Choi WS, Kim O, et al. Gastrokine 1 inhibits the carcinogenic potentials of Helicobacter pylori CagA. Carcinogenesis. 2014; 35: 2619-29.
Shen J, Xiao Z, Wu WK, Wang MH, To KF, Chen Y, et al. Epigenetic silencing of miR-490-3p reactivates the chromatin remodeler SMARCD1 to promote Helicobacter pylori-induced gastric carcinogenesis. Cancer Res 2014 in press.
Brandt S, Kwok T, Hartig R, Konig W, Backert S. NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci USA 2005; 102: 9300-5.
Guilford PJ, Hopkins JB, Grady WM, Markowitz SD, Willis J, Lynch H, et al. E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat 1999; 14: 249-55.
Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, et al. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res 1994; 54: 3845-52.
Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 1995; 19: 37-43.
You WC, Brown LM, Zhang L, Li JY, Jin ML, Chang YS, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst 2006; 98: 974-83.
Ito M, Haruma K, Kamada T, Mihara M, Kim S, Kitadai Y, et al. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther 2002; 16: 1449-56.
Wang J, Xu L, Shi R, Huang X, Li SW, Huang Z, et al. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion 2011; 83: 253-60.
Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, et al; Asia-Pacific Gastric Cancer Consensus Conference. Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol 2008; 23: 351-65.
Ladeiras-Lopes R, Pereira AK, Nogueira A, Pinheiro-Torres T, Pinto I,Santos-Pereira R, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control 2008; 19: 689-701.
Tramacere I, Negri E, Pelucchi C, Bagnardi V, Rota M, Scotti L, et al. A meta-analysis on alcohol drinking and gastric cancer risk. Ann Oncol 2012; 23: 28-36.
Zhang Z, Xu G, Ma M, Yang J, Liu X. Dietary fiber intake reduces risk for gastric cancer: a meta-analysis. Gastroenterology 2013; 145: 113-20.
Shin CM, Kim N, Yang HJ, Cho SI, Lee HS, Kim JS, et al. Stomach cancer risk in gastric cancer relatives: interaction between Helicobacter pylori infection and family history of gastric cancer for the risk of stomach cancer. J Clin Gastroenterol 2010; 44: 34-9.
Brenner H, Arndt V, Stürmer T, Stegmaier C, Ziegler H, Dhom G. Individual and joint contribution of family history and Helicobacter pylori infection to the risk of gastric carcinoma. Cancer 2000; 88: 274-9.
Chen Y, Liu L, Wang X, Wang J, Yan Z, Cheng J, et al. Body mass index and risk of gastric cancer: a meta-analysis of a population with more than ten million from 24 prospective studies. Cancer Epidemiol Biomarkers Prev 2013; 22: 1395-408.
Mesquita P, Raquel A, Nuno L, Reis CA, Silva LF, Serpa J, et al. Metaplasia-a transdifferentiation process that facilitates cancer development: the model of gastric intestinal metaplasia. Crit Rev Oncog 2006; 12: 3-26.
Meining A, Morgner A, Miehlke S, Bayerdörffer E, Stolte M. Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis? Best Pract Res Clin Gastroenterol 2001; 15: 983-98.
Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis. Helicobacter 2007; 12: 32-8.
Wong BC, Zhang L, Ma JL, Pan KF, Li JY, Shen L, et al. Effects of selective COX-2 inhibitor and Helicobacter pylori eradication on precancerous gastric lesions. Gut 2012; 61: 812-8.
Massarrat S, Haj-Sheykholeslami A, Mohamadkhani A, Zendehdel N, Rakhshani N, Stolte M, 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 :664-9.
Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, Zarama G, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst 2000; 92: 1881-8.
Mera R, Fontham ET, Bravo LE, Bravo JC, Piazuelo MB, Camargo MC, et al. Long term follow up of patients treated for Helicobacter pylori infection. Gut 2005; 54: 1536-40.
Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O'Connor A, et al; European Society of Gastrointestinal Endoscopy; European Helicobacter Study Group; European Society of Pathology; Sociedade Portuguesa de Endoscopia Digestiva. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.
Leung WK, Lin SR, Ching JY, To KF, Ng EK, Chan FK, et al. Factors predicting progression of gastric intestinal metaplasia: results of a randomised coverbentiresamievatrial on Helicobacter pylori eradication. Gut 2004; 53: 1244-9.
Varis K, Sipponen P, Laxén F, Samloff IM, Huttunen JK, Taylor PR, et al. Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. Helsinki Gastritis Study Group. Scand J Gastroenterol 2000; 35: 950-6.
Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, et al; Japan Gast Study Group. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 2008; 372: 392-7.
Choi J, Kim SG, Yoon H, Im JP, Kim JS, Kim WH, et al. Eradication of Helicobacter pylori after endoscopic resection of gastric tumors does not reduce incidence of metachronous gastric carcinoma. Clin Gastroenterol Hepatol 2014; 12: 793-800.
Maehata Y, Nakamura S, Fujisawa K, Esaki M, Moriyama T, Asano K, et al. Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer. Gastrointest Endosc 2012; 75: 39-46.
