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Helicobacter pylori and Gastric Cancer: Timing and Impact of Preventive Measures

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Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Abstract

Helicobacter pylori (H. pylori) is a Gram negative spiraliform bacterium that is commonly found in the stomach. H. pylori infection is still one of the world’s most frequent infections, present in the stomachs of approximately one-half of the world’s people. H. pylori infection is etiologically linked to histologic chronic active gastritis, peptic ulcer disease, and primary B-cell gastric lymphoma (gastric MALT lymphoma) and represents the major risk factor for the development of sporadic non-cardia gastric cancer (GC) of both intestinal and diffuse type. Studies that have examined the impact of GC prevention through H. pylori eradication have shown mixed results, but recent data suggest that prevention is only efficacious in patients without intestinal metaplasia or dysplasia. This indicates that, like in Barrett’s esophagus, we need better clinical risk markers to indicate which patients are at greatest risk of developing cancer to guide clinical strategies. Furthermore, recent epidemiological data have suggested a possible contribution of H. pylori in modifying the risk of developing other gastrointestinal malignancies (including esophageal, pancreatic, hepatocellular, and colorectal cancer), although mechanistically these associations remain unexplained. We review clinically relevant aspects of H. pylori infection in the context of GC development as well as studies that have examined the impact of eradication on GC development and, lastly, discuss these recent epidemiological studies connecting H. pylori infection to extragastric gastrointestinal malignancies.

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References

  1. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histoclinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.

    CAS  PubMed  Google Scholar 

  2. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol. 2010;25:479–86.

    Article  CAS  PubMed  Google Scholar 

  3. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  4. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013. http://globocan.iarc.fr.

    Google Scholar 

  5. Carneiro F. Stomach cancer. In: Steward BW, Wild CP, editors. World cancer report 2014. Lyon: International Agency for Research on Cancer; 2014. p. 383–91.

    Google Scholar 

  6. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.

    Article  CAS  PubMed  Google Scholar 

  7. Asaka M, Kato M, Sakamoto N. Roadmap to eliminate gastric cancer with Helicobacter pylori eradication and consecutive surveillance in Japan. J Gastroenterol. 2014;49:1–8.

    Article  CAS  PubMed  Google Scholar 

  8. Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer. 2007;10(2):75–83.

    Article  PubMed  Google Scholar 

  9. Jakszyn P, Bingham S, Pera G, Riboli E, Gonzalez CA, et al. Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study. Carcinogenesis. 2006;27(7):1497–501.

    Article  CAS  PubMed  Google Scholar 

  10. O’Doherty MG, Freedman ND, Hollenbeck AR, et al. A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study. Gut. 2012;61:1261–8.

    Article  PubMed  Google Scholar 

  11. Ladeiras-Lopes R, Pereira AK, Nogueira A, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control. 2008;19:689–701.

    Article  PubMed  Google Scholar 

  12. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014;23:700–13.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Malfertheiner P, Link A, Selgrad M. Helicobacter pylori: perspectives and time trends. Nat Rev Gastroenterol Hepatol. 2014;11(10):628–38.

    PubMed  Google Scholar 

  14. IARC Working Group. IARC monographs on the evaluation of carcinogenic risk to humans. Schistosomes, liver flukes and Helicobacter Pylor, vol. 61. IARC: Lyon, France; 1994.

    Google Scholar 

  15. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt B):1–441.

    Google Scholar 

  16. Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M. A model for gastric cancer epidemiology. Lancet. 1975;2:58–60.

    Article  CAS  PubMed  Google Scholar 

  17. El-Omar EM, Oien K, El Nujumi A, Gillen D, Wirz A, Dahill S, Williams C, Ardill JE, McColl KE. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology. 1997;113:15–24.

    Article  CAS  PubMed  Google Scholar 

  18. Uemura N, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–9.

    Article  CAS  PubMed  Google Scholar 

  19. Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World J Gastroenterol. 2012;18(12):1279–85.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology. 2003;125:1636.

    Article  PubMed  Google Scholar 

  21. Ford AC, Forman D, Hunt RH, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2104;348:3174.

    Article  Google Scholar 

  22. Chen HN, Wang Z, Li X, Zhou ZG. Helicobacter pylori eradication cannot reduce the risk of gastric cancer in patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis. Gastric Cancer. 2015;22. Epub ahead of print.

    Google Scholar 

  23. Venerito M, Malfertheiner P. Preneoplastic conditions in the stomach: always a point of no return? Dig Dis. 2105;33(1):5–10.

    Article  Google Scholar 

  24. Shiotani A, Haruma K, Graham DY. Metachronous gastric cancer after successful Helicobacter pylori eradication. World J Gastroenterol. 2014;20(33):11552–9.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M. 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.

    Article  PubMed  Google Scholar 

  26. Choi J, Kim SG, Yoon H, Im JP, Kim JS, Kim WH, Jung HC. 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.

    Article  PubMed  Google Scholar 

  27. Herrero R, Park JY, Forman D. The fight against gastric cancer—the IARC Working Group report. Best Pract Res Clin Gastroenterol. 2014;28(6):1107–14.

    Article  PubMed  Google Scholar 

  28. Cho E, Kang MH, Choi KS, Suh M, Jun JK, Park EC. Cost-effectiveness outcomes of the national gastric cancer screening program in South Korea. Asian Pac J Cancer Prev. 2013;14(4):2533–40.

    Article  PubMed  Google Scholar 

  29. Lu YL, Lui LY, Wu Q, Lui WD, Li SJ, Cao CQ, et al. Comparison of two cancer screening schemes in a high-risk population. Chin J Oncol. 2012;35:394e7.

    Google Scholar 

  30. Malfertheiner P, Selgrad M. Gastric cancer screening in conjunction with colorectal cancer screening in Europe (GACSE). Clin Stud Protoc Version 1. 2013.

    Google Scholar 

  31. Leja M, Herrero R, Park JY, Plummer M. Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (gastric cancer prevention study by predicting atrophic gastritis; GISTAR). In: Helicobacter pylori eradication as a strategy for preventing gastric cancer. IARC Helicobacter pylori Working Group. Lyon, France: International Agency for Research on Cancer (IARC Working Group Reports, No. 8); 2014. Ch 4.2., p. 1474–1153.

    Google Scholar 

  32. Newton M, Bryan R, Burnham WR, Kamm MA. Evaluation of Helicobacter pylori in reflux oesophagitis and Barrett’s oesophagus. Gut. 1997;40:9–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chow WH, Blaser MJ, Blot WJ, Gammon MD, et al. An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res. 1998;58(4):588–90.

    CAS  PubMed  Google Scholar 

  34. Nie S, Chen T, Yang X, Huai P, Lu M. Association of Helicobacter pylori infection with esophageal adenocarcinoma and squamous cell carcinoma: a meta-analysis. Dis Esophagus. 2014;27(7):645–53.

    Article  CAS  PubMed  Google Scholar 

  35. Nguyen TH, Thrift AP, Ramsey D, Green L, Shaib YH, Graham DY, El-Serag HB. Risk factors for Barrett’s esophagus compared between African Americans and non-Hispanic Whites. Am J Gastroenterol. 2014;109(12):1870–80.

    Article  PubMed  Google Scholar 

  36. Fujita M, Nakamura Y, Kasashima S, Furukawa M, Misaka R, Nagahara H. Risk factors associated with Barrett’s epithelial dysplasia. World J Gastroenterol. 2014;20(15):4353–61.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. Relationship between Helicobacter pylori infection and esophageal neoplasia: a meta-analysis. Clin Gastroenterol Hepatol. 2007;5(12):1413–7.

    Article  PubMed  Google Scholar 

  38. Lee JW, Lee DH, Lee JI, Jeong S, Song SY, et al. Identification of Helicobacter pylori in gallstone, bile, and other hepatobiliary tissues of patients with cholecystitis. Gut Liver. 2010;4(1):60–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Murphy G, Michel A, Taylor PR, Albanes D, Weinstein SJ, Virtamo J, Parisi D, Snyder K, Butt J, McGlynn KA, Koshiol J, Pawlita M, Lai GY, Abnet CC, Dawsey SM, Freedman ND. Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study. Hepatology. 2014;60(6):1963–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hassan EH, Gerges SS, El-Atrebi KA, El-Bassyouni HT. The role of H. pylori infection in gall bladder cancer: clinicopathological study. Tumour Biol. [Epub ahead of print]. Accessed 16 Apr 2015.

    Google Scholar 

  41. Schulte A, Pandeya N, Fawcett J, Fritschi L, Risch HA, Webb PM, Whiteman DC, Neale RE. Association between Helicobacter pylori and pancreatic cancer risk: a meta-analysis. Cancer Causes Control. 2015;26(7):1027–35.

    Article  PubMed  Google Scholar 

  42. Sonnenberg A, Genta RM. Helicobacter pylori is a risk factor for colonic neoplasms. Am J Gastroenterol. 2013;108(2):208–15.

    Article  PubMed  Google Scholar 

  43. Brim H, Zahaf M, Laiyemo AO, Nouraie M, Pérez-Pérez GI, Smoot DT, Lee E, Razjouyan H, Ashktorab H. Gastric Helicobacter pylori infection associates with an increased risk of colorectal polyps in African Americans. BMC Cancer. 2014;14:296.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Patel S, Lipka S, Shen H, Barnowsky A, Silpe J, Krishnamachari B, et al. The association of H. pylori and colorectal adenoma: does it exist in the US Hispanic population? J Gastrointest Oncol. 2014;5(6):463–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Guo Y, Li HY. Association between Helicobacter pylori infection and colorectal neoplasm risk: a meta-analysis based on East Asian population. J Cancer Res Ther. 2014;10(Suppl):263–6.

    Article  PubMed  Google Scholar 

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Correspondence to Peter Malfertheiner M.D. .

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Venerito, M., Vasapolli, R., Malfertheiner, P. (2016). Helicobacter pylori and Gastric Cancer: Timing and Impact of Preventive Measures. In: Jansen, M., Wright, N. (eds) Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract. Advances in Experimental Medicine and Biology, vol 908. Springer, Cham. https://doi.org/10.1007/978-3-319-41388-4_20

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