H. pylori infection and gastric cancer: State of the art (Review)

Conteduca,Vincenza; Sansonno,Domenico; Lauletta,Gianfranco; Russi,Sabino; Ingravallo,Giuseppe; Dammacco,Franco

doi:10.3892/ijo.2012.1701

H. pylori infection and gastric cancer: State of the art (Review)

Authors:
- Vincenza Conteduca
- Domenico Sansonno
- Gianfranco Lauletta
- Sabino Russi
- Giuseppe Ingravallo
- Franco Dammacco
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Affiliations: Department of Internal Medicine and Clinical Oncology, University of Bari ‘Aldo Moro’ Medical School, Bari, Italy, Department of Pathology, University of Bari ‘Aldo Moro’ Medical School, Bari, Italy
Published online on: November 15, 2012 https://doi.org/10.3892/ijo.2012.1701
Pages: 5-18

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Abstract

Gastric cancer (GC) is one of the leading types of cancer worldwide, particularly in East Asian populations. Helicobacter pylori (HP) infection has been established as a major risk factor for GC. Although more than 50% of the world population is infected with this bacterium, less than 2% develop GC. Therefore, further risk factors (such as host genetic polymorphisms and lifestyle, as well as environmental and epigenetic factors) may also play a role in its occurrence. The correlation between HP infection and GC represents a typical model of a multi‑step process, characterized by some pre-neoplastic lesions with a high risk of progression (atrophic gastritis, intestinal metaplasia and dysplasia). In addition, HP also plays an oncogenic role in the development of mucosa‑associated lymphoid tissue (MALT) lymphoma, that accounts for approximately 3% of all gastric tumors. Hyperplastic polyps often arise in patients with atrophic gastric mucosa and HP‑associated gastritis (25% of cases); however, their malignant trasformation is rare (<3% of cases). A number of trials have demonstrated the possibility of cancer prevention through HP screening and eradication, particularly in high‑risk populations, whereas it may not be cost‑effective in areas of low risk. In this review, we discuss i) the complex pathogenetic mechanisms of gastric carcinogenesis in which HP is involved; ii) the main approaches to the diagnosis, prevention, surveillance and treatment of pre-malignant lesions associated with HP infection; iii) the most effective way to detect GC in its earlier stages; and iv) the most important contribution to reducing the burden of GC.

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1.	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2.	Kim SS, Ruiz VE, Carroll JD and Moss SF: Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma. Cancer Lett. 305:228–238. 2011. View Article : Google Scholar
3.	Suerbaum S and Michetti P: Helicobacter pylori infection. N Engl J Med. 347:1175–1186. 2002. View Article : Google Scholar
4.	Fuccio L, Eusebi LH and Bazzoli F: Gastric cancer, Helicobacter pylori infection and other risk factors. World J Gastrointest Oncol. 2:342–347. 2010.
5.	Conteduca V, Sansonno D, Ingravallo G, et al: Barrett’s esophagus and esophageal cancer: an overview. Int J Oncol. 41:414–424. 2012.
6.	Crew KD and Neugut AI: Epidemiology of gastric cancer. World J Gastroenterol. 12:354–362. 2006.
7.	Polk DB and Peek RM Jr: Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 10:403–414. 2010. View Article : Google Scholar
8.	Zullo A, Hassan C, Cristofari F, et al: Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol. 8:105–110. 2010.
9.	Fuccio L, Zagari RM, Eusebi LH, et al: Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 151:121–128. 2009.
10.	Yaghoobi M, Bijarchi R and Narod SA: Family history and the risk of gastric cancer. Br J Cancer. 102:237–242. 2010. View Article : Google Scholar : PubMed/NCBI
11.	IARC Working Group: Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans Lyon, 7–14 June 1994. IARC Monogr Eval Carcinog Risks Hum. 61:1–241. 1994.
12.	De Vries AC, Haringsma J and Kuipers EJ: The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection. Helicobacter. 12:1–15. 2007.PubMed/NCBI
13.	Correa P: A human model of gastric carcinogenesis. Cancer Res. 48:3554–3560. 1998.
14.	Watanabe T, Tada M, Nagai H, Sasaki S and Nakao M: Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology. 115:642–648. 1998. View Article : Google Scholar
15.	Correa P and Houghton J: Carcinogenesis of Helicobacter pylori. Gastroenterology. 133:659–672. 2007.
16.	Hatakeyama M: Helicobacter pylori CagA-a bacterial intruder conspiring gastric carcinogenesis. Int J Cancer. 119:1217–1223. 2006. View Article : Google Scholar
17.	Konturek PC, Konturek SJ and Brzozowski T: Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 60:3–21. 2009.
18.	Gianfagna F, De Feo E, van Duijn CM, Ricciardi G and Boccia S: A systematic review of meta-analyses on gene polymorphisms and gastric cancer risk. Curr Genomics. 9:361–374. 2008. View Article : Google Scholar : PubMed/NCBI
19.	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. 106:867–874. 2011.
20.	Liu D, He Q and Liu C: Correlations among Helicobacter pylori infection and the expression of cyclooxygenase-2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia. J Gastroenterol Hepatol. 25:795–799. 2010.
21.	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. 132:905–912. 2007. View Article : Google Scholar : PubMed/NCBI
22.	Nobili S, Bruno L, Landini I, et al: Genomic and genetic alterations influence the progression of gastric cancer. World J Gastroenterol. 17:290–299. 2011. View Article : Google Scholar : PubMed/NCBI
23.	Lu XX, Yu JL, Ying LS, et al: Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression. Cancer. 118:5507–5517. 2012. View Article : Google Scholar : PubMed/NCBI
24.	Rocco A, Compare D and Nardone G: Cancer stem cell hypothesis and gastric carcinogenesis: Experimental evidence and unsolved questions. World J Gastrointest Oncol. 4:54–59. 2012. View Article : Google Scholar : PubMed/NCBI
25.	Suarez F, Lortholary O, Hermine O, et al: Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood. 107:3034–3044. 2006. View Article : Google Scholar : PubMed/NCBI
26.	Carmack SW, Genta RM, Graham DY and Lauwers GY: Management of gastric polyps: a pathology-based guide for gastroenterologists. Nat Rev Gastroenterol Hepatol. 6:331–341. 2009. View Article : Google Scholar
27.	Kelly PJ and Lauwers GY: Clinical guidelines: Consensus for the management of patients with gastric polyps. Nat Rev Gastroenterol Hepatol. 8:7–8. 2011. View Article : Google Scholar : PubMed/NCBI
28.	Malfertheiner P, Megraud F, O’Morain C, et al: Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 56:772–781. 2007.PubMed/NCBI
29.	Malfertheiner P, Megraud F, O’Morain CA, et al: Management of Helicobacter pylori infection - the Maastricht IV/ Florence Consensus Report. Gut. 61:646–664. 2012.
30.	De Vries AC and Kuipers EJ: Epidemiology of premalignant gastric lesions: implications for the development of screening and surveillance strategies. Helicobacter. 12:22–31. 2007.PubMed/NCBI
31.	Schlemper RJ, Itabashi M, Kato Y, et al: Differences in diagnostic criteria for gastric carcinoma between Japanese and western pathologists. Lancet. 349:1725–1729. 1997. View Article : Google Scholar : PubMed/NCBI
32.	Schlemper RJ, Riddell RH, Kato Y, et al: The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 47:251–255. 2000. View Article : Google Scholar : PubMed/NCBI
33.	Dixon MF: Gastrointestinal epithelial neoplasia: Vienna revisited. Gut. 51:130–131. 2002. View Article : Google Scholar : PubMed/NCBI
34.	Rugge M, Pennelli G, Pilozzi E, et al: Gastritis: the histology report. Dig Liver Dis. 43(Suppl 4): S373–S384. 2011. View Article : Google Scholar
35.	Ohnita K, Isomoto H, Shikuwa S, et al: Magnifying chromoendoscopic findings of early gastric cancer and gastric adenoma. Dig Dis Sci. 56:2715–2722. 2011. View Article : Google Scholar : PubMed/NCBI
36.	Yeh JM, Hur C, Kuntz KM, Ezzati M and Goldie SJ: Cost-effectiveness of treatment and endoscopic surveillance of precancerous lesions to prevent gastric cancer. Cancer. 116:2941–2953. 2010. View Article : Google Scholar : PubMed/NCBI
37.	Hamashima C, Shibuya D, Yamazaki H, et al: The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol. 38:259–267. 2008. View Article : Google Scholar
38.	Fock KM, Katelaris P, Sugano K, et al: Second Asia-Pacific consensus guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol. 24:1587–1600. 2009. View Article : Google Scholar : PubMed/NCBI
39.	Zullo A, Hassan C, Cristofari F, Perri F and Morini S: Gastric low-grade mucosal-associated lymphoid tissue-lymphoma: Helicobacter pylori and beyond. World J Gastrointest Oncol. 2:181–186. 2010. View Article : Google Scholar : PubMed/NCBI
40.	Oh SY, Kim WS, Kim JS, et al: Multiple mucosa-associated lymphoid tissue organs involving marginal zone B cell lymphoma: organ-specific relationships and the prognostic factors. Consortium for improving survival of lymphoma study. Int J Hematol. 92:510–517. 2010. View Article : Google Scholar
41.	Shinagare AB, Ramaiya NH, O’Regan K, Jagannathan JP, Hornick JL and LaCasce AS: Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma. J Clin Oncol. 29:297–300. 2011. View Article : Google Scholar
42.	Zucca E and Dreyling M; ESMO Guidelines Working Group: Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21(Suppl 5): v175–v176. 2010. View Article : Google Scholar
43.	Ruskoné-Fourmestraux A, Fischbach W, Aleman BM, et al: EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. Gut. 60:747–758. 2011.PubMed/NCBI
44.	Goddard AF, Badreldin R, Pritchard DM, et al: British Society of Gastroenterology: The management of gastric polyps. Gut. 59:1270–1276. 2010. View Article : Google Scholar : PubMed/NCBI
45.	Fitzgeral RC, Hardwick R, Huntsman D, et al: Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 47:436–444. 2010. View Article : Google Scholar : PubMed/NCBI
46.	Guilford P, Humar B and Blair V: Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice. Gastric cancer. 13:1–10. 2010. View Article : Google Scholar : PubMed/NCBI
47.	Bornschein J, Rokkas T, Selgrad M and Malfertheiner P: Helicobacter pylori and clinical aspects of gastric cancer. Helicobacter. 14(Suppl 1): 41–45. 2009. View Article : Google Scholar
48.	Fukase K, Kato M, Kikuchi S, et al: 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. 372:392–397. 2008.PubMed/NCBI
49.	Take S, Mizuno M, Ishiki K, et al: The long-term risk of gastric cancer after the successful eradication of Helicobacter pylori. J Gastroenterol. 46:318–324. 2011. View Article : Google Scholar : PubMed/NCBI
50.	Kodama M, Murakami K, Okimoto T, et al: Helicobacter pylori eradication improves gastric atrophy and intestinal metaplasia in long-term observation. Digestion. 85:126–130. 2012. View Article : Google Scholar
51.	Correa P, Fontham ET, Bravo JC, et al: Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J Natl Cancer Inst. 92:1881–1888. 2000. View Article : Google Scholar : PubMed/NCBI
52.	Wong BC, Lam SK, Wong WM, et al: Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 291:187–194. 2004. View Article : Google Scholar
53.	Leung WK, Lin SR, Ching JY, et al: Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut. 53:1244–1249. 2004. View Article : Google Scholar : PubMed/NCBI
54.	Mera R, Fontham ET, Bravo LE, et al: Long term follow up of patients treated for Helicobacter pylori infection. Gut. 54:1536–1540. 2005. View Article : Google Scholar : PubMed/NCBI
55.	Zhou LY, Lin SR, Ding SG, et al: The changing trends of the incidence of gastric cancer after Helicobacter pylori eradication in Shandong area. Chin J Dig Dis. 6:114–115. 2005. View Article : Google Scholar : PubMed/NCBI
56.	You WC, Brown LM, Zhang L, et al: Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 98:974–983. 2006. View Article : Google Scholar
57.	Kato M, Asaka M, Nakamura T, et al: Helicobacter pylori eradication prevents the development of gastric cancer - results of a long-term retrospective study in Japan. Aliment Pharmacol Ther. 24:203–206. 2006. View Article : Google Scholar
58.	Take S, Mizuno M, Ishiki K, et al: Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases. J Gastroenterol. 42(Suppl 17): 21–27. 2007. View Article : Google Scholar : PubMed/NCBI
59.	Takenaka R, Okada H, Kato J, et al: Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type. Aliment Pharmacol Ther. 25:805–812. 2007. View Article : Google Scholar
60.	Ogura K, Hirata Y, Yanai A, et al: The effect of Helicobacter pylori eradication on reducing the incidence of gastric cancer. J Clin Gastroenterol. 42:279–283. 2008.
61.	Mabe K, Takahashi M, Oizumi H, et al: Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer? World J Gastroenterol. 15:4290–4297. 2009.
62.	Kuo SH, Yeh KH, Wu MS, et al: Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 119:4838–4844. 2012. View Article : Google Scholar : PubMed/NCBI
63.	Park HS, Kim YJ, Yang WI, Suh CO and Lee YC: Treatment and outcome of localized Helicobacter pylori-negative low-grade gastric MALT lymphoma. World J Gastroenterol. 16:2158–2162. 2010.
64.	Gill H, Chim CS, Au WY, et al: Non-gastric marginal zone B cell lymphoma: clinicopathologic features and treatment results. Ann Hematol. 90:1399–1407. 2011. View Article : Google Scholar : PubMed/NCBI
65.	Owens SR and Smith LB: Molecular aspects of H. pylori-related MALT lymphoma. Patholog Res Int. 2011:1931492011.PubMed/NCBI
66.	O’Connor A, Gisbert JP, McNamara D and O’Morain C: Treatment of Helicobacter pylori infection 2010. Helicobacter. 15:46–52. 2010.
67.	Graham DY and Fischbach L: Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 59:1143–1153. 2010. View Article : Google Scholar
68.	Malfertheiner P, Bazzoli F, Delchier JC, et al: Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 377:905–913. 2011. View Article : Google Scholar
69.	Kang JM, Kim N, Lee DH, et al: Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage. J Gastroenterol Hepatol. 23:1287–1291. 2008.PubMed/NCBI
70.	Perri F, Manes G, Neri M, Vaira D and Nardone G: Helicobacter pylori antigen stool test and ¹³C-Urea breath test in patients after eradication treatments. Am J Gastroenterol. 97:2756–2762. 2002. View Article : Google Scholar : PubMed/NCBI
71.	World Gastroenterology Organisation: World Gastroenterology Organisation Global Guideline: Helicobacter pylori in developing countries. J Clin Gastroenterol. 45:383–388. 2011. View Article : Google Scholar
72.	Czinn SJ and Blanchard T: Vaccinating against Helicobacter pylori infection. Nat Rev Gastroenterol Hepatol. 8:133–140. 2011. View Article : Google Scholar
73.	Moss SF, Moise L, Lee DS, et al: HelicoVax: epitope-based therapeutic Helicobacter pylori vaccination in a mouse model. Vaccine. 29:2085–2091. 2011. View Article : Google Scholar : PubMed/NCBI
74.	Othman MO and Wallace MB: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in 2011, a Western perspective. Clin Res Hepatol Gastroenterol. 35:288–294. 2011. View Article : Google Scholar : PubMed/NCBI
75.	Pandalai PK, Lauwers GY, Chung DC, Patel D and Yoon SS: Prophylactic total gastrectomy for individuals with germline CDH1 mutation. Surgery. 149:347–355. 2011. View Article : Google Scholar : PubMed/NCBI
76.	Wu CY, Wu MS, Kuo KN, Wang CB, Chen YJ and Lin JT: Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori-infected patients. J Clin Oncol. 28:2952–2957. 2010. View Article : Google Scholar : PubMed/NCBI
77.	Navarro Silvera SA, Mayne ST, Risch HA, et al: Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer. Ann Epidemiol. 21:543–550. 2011.PubMed/NCBI