Gastric Cancer

, Volume 12, Issue 2, pp 79–87 | Cite as

Helicobacter pylori and gastric cancer

  • Hidekazu Suzuki
  • Eisuke Iwasaki
  • Toshifumi Hibi
Review Article


Helicobacter pylori is now well known as an important pathogen related to the development of gastric cancer. However, some clinicians still doubt the causal association of H. pylori with the development of gastric cancer. To summarize the recent clinical data on the link between H. pylori and gastric cancer, we reviewed related articles published over the past 3 years, after the award of the Nobel Prize for Physiology or Medicine to Drs. J.R. Warren and B.J. Marshall for the first culture and isolation of H. pylori and the investigation of their relevance to peptic ulcer disease. This updated summary of the relationship between H. pylori and gastric cancer highlights the strong link between the organism and the development of gastric cancer, and suggests eradication of this bacterial infection as a possible prophylactic measure against the development of this lethal malignancy. At present, clinicians and researchers in the field emphasize the strong need for H. pylori eradication from the human stomach.

Key words

Gastric cancer Helicobacter pylori Eradication Randomized controlled trial Gene polymorphism Food factor 


  1. 1.
    Suzuki H, Hibi T, Marshall BJ. Helicobacter pylori: present status and future prospects in Japan. J Gastroenterol 2007;42:1–15.PubMedCrossRefGoogle Scholar
  2. 2.
    Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983;I:1273–1275.Google Scholar
  3. 3.
    Suzuki H, Nishizawa T, Masaoka T, Mori M, Iwasaki E, Tsuchimoto K, et al. Helicobacter pylori infection and gastric cancer. JMAJ 2005;48:497–504.Google Scholar
  4. 4.
    IARC. Working Group on the Evaluation of Carcinogenic Risks to Humans. Helicobacter pylori. In: Schistosomes, liver flukes and Helicobacter pylori views and expert opinions of an IARC Working Group On The Evaluation of Carcinogenic Risks To Humans. Lyon: IARC 1994. p. 177–240.Google Scholar
  5. 5.
    Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, et al. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ 1991;302:1302–1305.PubMedCrossRefGoogle Scholar
  6. 6.
    Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 1991;325:1132–1136.PubMedGoogle Scholar
  7. 7.
    Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991;325:1127–1131.PubMedGoogle Scholar
  8. 8.
    Uemura N, Okamoto S, Yamamoto S, Yamaguchi S, Mashiba H, Taniyama K, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784–789.PubMedCrossRefGoogle Scholar
  9. 9.
    Yamagata H, Kiyohara Y, Aoyagi K, Kato I, Iwamoto H, Nakayama K, et al. Impact of Helicobacter pylori infection on gastric cancer incidence in a general Japanese population: the Hisayama study. Arch Intern Med 2000;160:1962–1968.PubMedCrossRefGoogle Scholar
  10. 10.
    Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 2004;291:187–194.PubMedCrossRefGoogle Scholar
  11. 11.
    Take S, Mizuno M, Ishiki K, Nagahara Y, Yoshida T, Yokota K, et al. The effect of eradicating Helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease. Am J Gastroenterol 2005;100:1037–1042.PubMedCrossRefGoogle Scholar
  12. 12.
    Huang JQ, Zheng GF, Sumanac K, Irvine EJ, Hunt RH. Metaanalysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003;125:1636–1644.PubMedCrossRefGoogle Scholar
  13. 13.
    Uemura N, Mukai T, Okamoto S, Yamaguchi S, Mashiba H, Taniyama K, et al. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer. Cancer Epidemiol Biomarkers Prev 1997;6:639–642.PubMedGoogle Scholar
  14. 14.
    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;98:974–983.PubMedGoogle Scholar
  15. 15.
    Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto 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 2008;372:392–397.PubMedCrossRefGoogle Scholar
  16. 16.
    Kim N, Park RY, Cho SI, Lim SH, Lee KH, Lee W, et al. Helicobacter pylori infection and development of gastric cancer in Korea: long-term follow-up. J Clin Gastroenterol 2008;42:448–454.PubMedCrossRefGoogle Scholar
  17. 17.
    Ji F, Wang ZW, Ning JW, Wang QY, Chen JY, Li YM. Effect of drug treatment on hyperplastic gastric polyps infected with Helicobacter pylori: a randomized, controlled trial. World J Gastroenterol 2006;12:1770–1773.PubMedGoogle Scholar
  18. 18.
    Wang C, Yuan Y, Hunt RH. The association between Helicobacter pylori infection and early gastric cancer: a meta-analysis. Am J Gastroenterol 2007;102:1789–1798.PubMedCrossRefGoogle Scholar
  19. 19.
    Take S, Mizuno M, Ishiki K, Nagahara Y, Yoshida T, Yokota 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 2007;42(Suppl 17):21–27.PubMedCrossRefGoogle Scholar
  20. 20.
    Takenaka R, Okada H, Kato J, Makidono C, Hori S, Kawahara Y, et al. Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type. Aliment Pharmacol Ther 2007;25:805–812.PubMedCrossRefGoogle Scholar
  21. 21.
    Ogura K, Hirata Y, Yanai A, Shibata W, Ohmae T, Mitsuno Y, et al. The effect of Helicobacter pylori eradication on reducing the incidence of gastric cancer. J Clin Gastroenterol 2008;42:279–283.PubMedGoogle Scholar
  22. 22.
    Gwack J, Shin A, Kim CS, Ko KP, Kim Y, Jun JK, et al. CagAproducing Helicobacter pylori and increased risk of gastric cancer: a nested case-control study in Korea. Br J Cancer 2006;95:639–641.PubMedCrossRefGoogle Scholar
  23. 23.
    Hansen S, Vollset SE, Derakhshan MH, Fyfe V, Melby KK, Aase S, et al. Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status. Gut 2007;56:918–925.PubMedCrossRefGoogle Scholar
  24. 24.
    Palli D, Masala G, Del Giudice G, Plebani M, Basso D, Berti D, et al. CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study. Int J Cancer 2007;120:859–867.PubMedCrossRefGoogle Scholar
  25. 25.
    Plummer M, van Doorn LJ, Franceschi S, Kleter B, Canzian F, Vivas J, et al. Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. J Natl Cancer Inst 2007;99:1328–1334.PubMedCrossRefGoogle Scholar
  26. 26.
    Masuda G, Tokunaga A, Shirakawa T, Togashi A, Kiyama T, Kato S, et al. Helicobacter pylori infection, but not genetic polymorphism of CYP2E1, is highly prevalent in gastric cancer patients younger than 40 years. Gastric Cancer 2007;10:98–103.PubMedCrossRefGoogle Scholar
  27. 27.
    Sasazuki S, Inoue M, Iwasaki M, Otani T, Yamamoto S, Ikeda S, et al. Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study. Cancer Epidemiol Biomarkers Prev 2006;15:1341–1347.PubMedCrossRefGoogle Scholar
  28. 28.
    Sawaya M, Yoshimura T, Shimoyama T, Munakata A, Fukuda S. Difference of p53AIP1 mRNA expression in gastric mucosa between patients with gastric cancer and chronic gastritis infected with Helicobacter pylori. J Clin Gastroenterol 2008;42:351–355.PubMedCrossRefGoogle Scholar
  29. 29.
    Tatemichi M, Sasazuki S, Inoue M, Tsugane S. Different etiological role of Helicobacter pylori (Hp) infection in carcinogenesis between differentiated and undifferentiated gastric cancers: a nested case-control study using IgG titer against Hp surface antigen. Acta Oncol 2008;47:360–365.PubMedCrossRefGoogle Scholar
  30. 30.
    Watanabe Y, Aoyama N, Sakai T, Shirasaka D, Maekawa S, Kuroda K, et al. HLA-DQB1 locus and gastric cancer in Helicobacter pylori infection. J Gastroenterol Hepatol 2006;21:420–424.PubMedCrossRefGoogle Scholar
  31. 31.
    Al-Moundhri MS, Al-Nabhani M, Al-Bahrani B, Burney IA, Al-Madhani A, Ganguly SS, et al. Interleukin-1 beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population. Gastric Cancer 2006;9:284–290.PubMedCrossRefGoogle Scholar
  32. 32.
    Garcia-Gonzalez MA, Strunk M, Piazuelo E, Benito R, Santolaria S, Jimenez P, et al. TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases. Genes Immun 2006;7:640–646.PubMedCrossRefGoogle Scholar
  33. 33.
    Hou L, El-Omar EM, Chen J, Grillo P, Rabkin CS, Baccarelli A, et al. Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer. Carcinogenesis 2007;28:118–123.PubMedCrossRefGoogle Scholar
  34. 34.
    Kubben FJ, Sier CF, Meijer MJ, van den Berg M, van der Reijden JJ, Griffioen G, et al. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. Br J Cancer 2006;95:744–751.PubMedCrossRefGoogle Scholar
  35. 35.
    Prasad KN, Saxena A, Ghoshal UC, Bhagat MR, Krishnani N. Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease. Ann Oncol 2008;19:1299–1303.PubMedCrossRefGoogle Scholar
  36. 36.
    Seno H, Satoh K, Tsuji S, Shiratsuchi T, Harada Y, Hamajima N, et al. Novel interleukin-4 and interleukin-1 receptor antagonist gene variations associated with non-cardia gastric cancer in Japan: comprehensive analysis of 207 polymorphisms of 11 cytokine genes. J Gastroenterol Hepatol 2007;22:729–737.PubMedGoogle Scholar
  37. 37.
    Shirai K, Ohmiya N, Taguchi A, Mabuchi N, Yatsuya H, Itoh A, et al. Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability. J Gastroenterol Hepatol 2006;21:1129–1135.PubMedCrossRefGoogle Scholar
  38. 38.
    Gonzalez CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti M, Boeing H, et al. Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPICEURGAST). Int J Cancer 2006;118:2559–2566.PubMedCrossRefGoogle Scholar
  39. 39.
    Gonzalez CA, Jakszyn P, Pera G, Agudo A, Bingham S, Palli D, et al. Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006;98:345–354.PubMedGoogle Scholar
  40. 40.
    Leung WK, Ng EK, Chan FK, Chan WY, Chan KF, Auyeung AC, et al. Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a randomized controlled trial. Clin Cancer Res 2006;12:4766–4772.PubMedCrossRefGoogle Scholar
  41. 41.
    Kim CG, Song HJ, Kook MC, Hong EK, Park S, Lee JY, et al. Preoperative versus post operative Helicobacter pylori eradication therapy in gastric cancer patients: a randomized trial. Am J Gastroenterol 2008;103:48–54.PubMedCrossRefGoogle Scholar
  42. 42.
    Tsai CJ, Herrera-Goepfert R, Tibshirani RJ, Yang S, Mohar A, Guarner J, et al. Changes of gene expression in gastric preneoplasia following Helicobacter pylori eradication therapy. Cancer Epidemiol Biomarkers Prev 2006;15:272–280.PubMedCrossRefGoogle Scholar
  43. 43.
    El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000;404:398–402.PubMedCrossRefGoogle Scholar
  44. 44.
    Zabaleta J, Camargo MC, Piazuelo MB, Fontham E, Schneider BG, Sicinschi LA, et al. Association of interleukin-1beta gene poly morphisms with precancerous gastric lesions in African Americans and Caucasians. Am J Gastroenterol 2006;101:163–171.PubMedCrossRefGoogle Scholar
  45. 45.
    Steenport M, Eom H, Uezu M, Schneller J, Gupta R, Mustafa Y, et al. Association of polymorphisms in myeloperoxidase and catalase genes with precancerous changes in the gastric mucosa of patients at inner-city hospitals in New York. Oncol Rep 2007;18:235–240.PubMedGoogle Scholar
  46. 46.
    Izzotti A, De Flora S, Cartiglia C, Are BM, Longobardi M, Camoirano A, et al. Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa. Carcinogenesis 2007;28:892–908.PubMedCrossRefGoogle Scholar
  47. 47.
    Humar B, Graziano F, Cascinu S, Catalano V, Ruzzo AM, Magnani M, et al. Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer. Oncogene 2002;21:8192–8195.PubMedCrossRefGoogle Scholar
  48. 48.
    Medina-Franco H, Ramos-De la Medina A, Vizcaino G, Medina-Franco JL. Single nucleotide polymorphisms in the promoter region of the E-cadherin gene in gastric cancer: case-control study in a young Mexican population. Ann Surg Oncol 2007;14:2246–2249.PubMedCrossRefGoogle Scholar
  49. 49.
    Jenab M, McKay JD, Ferrari P, Biessy C, Laing S, Munar GM, et al. CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Eur J Cancer 2008;44:774–780.PubMedCrossRefGoogle Scholar
  50. 50.
    Garcia-Gonzalez MA, Lanas A, Quintero E, Nicolas D, Parra-Blanco A, Strunk M, et al. Gastric cancer susceptibility is not linked to pro-and anti-inflammatory cytokine gene polymorphisms in whites: a Nationwide Multicenter Study in Spain. Am J Gastroenterol 2007;102:1878–1892.PubMedCrossRefGoogle Scholar
  51. 51.
    Asaka M, Satoh K, Sugano K, Sugiyama T, Takahashi S, Fukuda Y, et al. Guidelines in the management of Helicobacter pylori infection in Japan. Helicobacter 2001;6:177–186.PubMedCrossRefGoogle Scholar
  52. 52.
    Lind T, Veldhuyzen van Zanten S, Unge P, Spiller R, Bayerdorffer E, O’Morain C, et al. Eradication of Helicobacter pylori using 1-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study. Helicobacter 1996;1:138–144.PubMedCrossRefGoogle Scholar
  53. 53.
    Nishizawa T, Suzuki H, Kurabayashi K, Masaoka T, Muraoka H, Mori M, et al. Gatifloxacin resistance and mutations in gyrA after unsuccessful Helicobacter pylori eradication in Japan. Antimicrob Agents Chemother 2006;50:1538–1540.PubMedCrossRefGoogle Scholar
  54. 54.
    Miyaji H, Azuma T, Ito S, Suto H, Ito Y, Yamazaki Y, et al. Susceptibility of Helicobacter pylori isolates to metronidazole, clarithromycin and amoxycillin in vitro and in clinical treatment in Japan. Aliment Pharmacol Ther 1997;11:1131–1136.PubMedCrossRefGoogle Scholar
  55. 55.
    Nishizawa T, Suzuki H, Masaoka T, Iwasaki E, Hibi T. A new eradication resistance index as a predictor of metronidazole-containing second-line treatment of Helicobacter pylori. Digestion 2007;76:215–220.PubMedCrossRefGoogle Scholar
  56. 56.
    Masaoka T, Suzuki H, Kurabayashi K, Nomoto Y, Nishizawa T, Mori M, et al. Could frameshift mutations in the frxA and rdxA genes of Helicobacter pylori be a marker for metronidazole resistance? Aliment Pharmacol Ther 2006;24(Suppl. 4):81–87.Google Scholar
  57. 57.
    Matsuhisa T, Kawai T, Masaoka T, Suzuki H, Ito M, Kawamura Y, et al. Efficacy of metronidazole as second-line drug for the treatment of Helicobacter pylori infection in the Japanese population: a multicenter study in the Tokyo metropolitan area. Helicobacter 2006;11:152–158.PubMedCrossRefGoogle Scholar
  58. 58.
    Rokkas T, Sechopoulos P, Robotis I, Margantinis G, Pistiolas D. Cumulative H. pylori eradication rates in clinical practice by adopting first and second-line regimens proposed by the Maastricht III Consensus and a third-line empirical regimen. Am J Gastroenterol 2009;104:21–25.PubMedCrossRefGoogle Scholar
  59. 59.
    Nishizawa T, Suzuki H, Hibi T. Quinolone-based third-line therapy for Helicobacter pylori eradication. J Clin Biochem Nutri 2009;44:119–124.CrossRefGoogle Scholar
  60. 60.
    Suzuki H, Nishizawa T, Muraoka H, Hibi T. Sitafloxacin and garenoxacin may overcome the antibiotic resistance of Helicobacter pylori with gyrA mutation. Antimicrob Agents Chemother 2009;53:1720–1721.PubMedCrossRefGoogle Scholar
  61. 61.
    Gonzalez Carro P, Perez Roldan F, De Pedro Esteban A, Legaz Huidobro ML, Soto Fernandez S, Roncero Garcia Escribano O, et al. Efficacy of rifabutin-based triple therapy in Helicobacter pylori infected patients after two standard treatments. J Gastroenterol Hepatol 2007;22:60–63.PubMedCrossRefGoogle Scholar
  62. 62.
    Suzuki S, Suzuki H, Nishizawa T, Kaneko F, Ootani S, Muraoka H, et al. Past rifampicin dosing determines rifabutin resistance of Helicobacter pylori. Digestion 2009;79:1–4.PubMedCrossRefGoogle Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2009

Authors and Affiliations

  • Hidekazu Suzuki
    • 1
  • Eisuke Iwasaki
    • 1
  • Toshifumi Hibi
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan

Personalised recommendations