Abstract
Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. We conducted a systematic review concerning gastric cancer development after H. pylori eradication therapy. In total 15 papers matched our criteria, the results were reviewed. The H. pylori eradication therapy statistically diminished the prevalence of clinical gastric cancer by approximately one-third. The studies from Japan supported this conclusion; however, studies from overseas reported conflicting results. The differences in these conclusions lie in the diagnostic ability of endoscopic examination, since the clinical stage was quite different between these studies. Gastric cancer that developed after eradication revealed a mainly intestinal type histology and depressed-type appearance. The following are possible reasons for reduced gastric cancer: (1) eradication therapy inhibits the new occurrence of gastric cancer, (2) eradication regresses or inhibits the growth of gastric cancer, and (3) eradication interferes with the discovery of gastric cancer. Considering the biological nature of cancer cell proliferation, a sufficiently long-term follow-up may clarify the effect of eradication therapy on inhibition of the development (not discovery) of gastric cancer and reduction of gastric cancer-related mortality.
Similar content being viewed by others
References
Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Publ. 2004;(157):327–49.
Sakamoto H, Yoshimura K, Saeki N, Katai H, Shimoda T, Matsuno Y, et al. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet. 2008;40:730–40.
Oue N, Hamai Y, Mitani Y, Matsumura S, Oshimo Y, Aung PP, et al. Gene expression profile of gastric carcinoma: identification of genes and tags potentially involved in invasion, metastasis, and carcinogenesis by serial analysis of gene expression. Cancer Res. 2004;64:2397–405.
Goodman KJ, Cockburn M. The role of epidemiology in understanding the health effects of Helicobacter pylori. Epidemiology. 2001;12:266–71.
Suzuki H, Hibi T, Marshall BJ. Helicobacter pylori: present status and future prospects in Japan. J Gastroenterol. 2007;42:1–15.
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;325:1132–6.
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;325:1127–31.
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. 1994;61:1–241.
Correa P. Helicobacter pylori and gastric cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:238s–41s.
Kawaguchi H, Haruma K, Komoto K, Yoshihara M, Sumii K, Kajiyama G. Helicobacter pylori infection is the major risk factor for atrophic gastritis. Am J Gastroenterol. 1996;91:959–62.
Haruma K, Komoto K, Kawaguchi H, Okamoto S, Yoshihara M, Sumii K, et al. Pernicious anemia and Helicobacter pylori infection in Japan: evaluation in a country with a high prevalence of infection. Am J Gastroenterol. 1995;90:1107–10.
Ito M, Haruma K, Kaya S, Kamada T, Kim S, Sasaki A, et al. Role of anti-parietal cell antibody in Helicobacter pylori-associated atrophic gastritis: evaluation in a country of high prevalence of atrophic gastritis. Scand J Gastroenterol. 2002;37:287–93.
Komoto K, Haruma K, Kamada T, Tanaka S, Yoshihara M, Sumii K, et al. Helicobacter pylori infection and gastric neoplasia: correlations with histological gastritis and tumor histology. Am J Gastroenterol. 1998;93:1271–6.
Haruma K, Komoto K, Kamada T, Ito M, Kitadai Y, Yoshihara M, et al. Helicobacter pylori is a major risk factor for gastric carcinoma in young patients. Scand J Gastroenterol. 2000;35:255–9.
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.
Hatakeyama M. Helicobacter pylori and gastric carcinogenesis, J Gastroenterol 2009 (in press).
Higashi H, Yokoyama K, Fujii Y, Ren S, Yuasa H, Saadat I, et al. Epiya motif is a membrane targeting signal of Helicobacter pylori CagA in mammalian cells. J Biol Chem. 2005;280:23130–7.
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.
Kato S, Matsukura N, Tsukada K, Matsuda N, Mizoshita T, Tsukamoto T, et al. Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics. Cancer Sci. 2007;98:790–4.
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;291:187–94.
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 trial on Helicobacter pylori eradication. Gut. 2004;53:1244–9.
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.
Zhou LY, Lin SR, Ding SG, Huang XB, Zhang L, Meng LM, et al. The changing trends of the incidence of gastric cancer after Helicobacter pylori eradication in Shandong area. Chin J Dig Dis. 2005;6:114–5.
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.
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;6:639–42.
Kato M, Asaka M, Nakamura T, Azuma T, Tomita E, Kamoshida T, et al. Significance of Helicobacter pylori eradication on incidence of gastric cancer. Aliment Pharmacol Ther. 2006;24(suppl 4):203–6.
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;100:1037–42.
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):21–7.
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;25:805–12.
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;42:279–83.
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;372:350–2.
Kokkola A, Sipponen P, Arkkila P, Danielson H, Puolakkainen P. Does the eradication of Helicobacter pylori delay the diagnosis of gastric cancer? Scand J Gastroenterol. 2008;43:1456–60.
Kamada T, Hata J, Sugiu K, Kusunoki H, Ito M, Tanaka S, et al. Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9-year prospective follow-up study in Japan. Aliment Pharmacol Ther. 2005;21:1121–6.
Takata S, Ito M, Yoshihara M, Tanaka S, Imagawa S, Haruma K, et al. Host factors contributing to the discovery of gastric cancer after successful eradication therapy of Helicobacter pylori: preliminary report. J Gastroenterol Hepatol. 2007;22:571–6.
Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, et al. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med. 2007;13:470–6.
Naito Y, Yoshikawa T. Molecular and cellular mechanisms involved in Helicobacter pylori-induced inflammation and oxidative stress. Free Radic Biol Med. 2002;33:323–36.
Naito Y, Takagi T, Yoshikawa T. Molecular fingerprints of neutrophil-dependent oxidative stress in inflammatory bowel disease. J Gastroenterol. 2007;42:787–98.
Ley C, Mohar A, Guarner J, Herrera-Goepfert R, Figueroa LS, Halperin D, et al. Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial. Cancer Epidemiol Biomarkers Prev. 2004;13:4–10.
Sung JJ, Lin SR, Ching JY, Zhou LY, To KF, Wang RT, et al. Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a prospective, randomized study. Gastroenterology. 2000;119:7–14.
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.
Haruma K, Mihara M, Okamoto E, Kusunoki H, Hananoki M, Tanaka S, et al. Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus. Evaluation of 24-h pH monitoring. Aliment Pharmacol Ther. 1999;13:155–62.
Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, et al. Improvement of atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001;134:380–6.
Sugiyama T, Sakaki N, Kozawa H, Sato R, Fujioka T, Satoh K, et al. Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment. Aliment Pharmacol Ther. 2002;16(suppl 2):187–90.
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.
Gotoda T, Saito D, Kondo H, Ono H, Oda I, Fujishiro M, et al. Endoscopic and histological reversibility of gastric adenoma after eradication of Helicobacter pylori. J Gastroenterol. 1999;34(Suppl 11):91–6.
Haruma K, Suzuki T, Tsuda T, Yoshihara M, Sumii K, Kajiyama G. Evaluation of tumor growth rate in patients with early gastric carcinoma of the elevated type. Gastrointest Radiol. 1991;16:289–92.
Sasaki A, Kitadai Y, Ito M, Sumii M, Tanaka S, Yoshihara M, et al. Helicobacter pylori infection influences tumor growth of human gastric carcinomas. Scand J Gastroenterol. 2003;38:153–8.
Suzuki M, Suzuki H, Masaoka T, Tanaka S, Suzuki K, Ishii H. Helicobacter pylori eradication treatment modulates epithelial cell proliferation and tissue content of hepatocyte growth factor in the gastric mucosa. Aliment Pharmacol Ther. 2004;20(suppl 1):158–64.
Naito Y, Ito M, Suzuki H, Watanabe T. Biomarkers in patients with gastric inflammation: a systematic review. Digestion. 2005;72:164–80.
Ito M, Tanaka S, Takata S, Oka S, Imagawa S, Ueda H, et al. Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up. Aliment Pharmacol Ther. 2005;21:559–66.
Ito M, Tanaka S, Maeda M, Takamura A, Tatsugami M, Wada Y, et al. Role of the gastrin-gastrin receptor system in the expansive growth of human gastric neoplasms. Digestion. 2008;78:163–70.
Tsuji N, Ishiguro S, Matsumura M, Yoshisato K, Umehara Y, Kudo M. Clinico-pathological time trends for early gastric cancer and Helicobacter pylori infection. Stomach Intest. 2007;42:931–6 (in Japanese).
Yoshihara M, Hiyama T, Yoshida S, Ito M, Tanaka S, Watanabe Y, et al. Reduction in gastric cancer mortality by screening based on serum pepsinogen concentration: a case-control study. Scand J Gastroenterol. 2007;42:760–4.
Miyamoto M, Haruma K, Yoshihara M, Sumioka M, Nishisaka T, Tanaka S, et al. Five cases of nodular gastritis and gastric cancer: a possible association between nodular gastritis and gastric cancer. Dig Liver Dis. 2002;34:819–20.
Kamada T, Miyamoto M, Ito M, Sugiu K, Kusunoki H, Hata J, et al. Nodular gastritis is a risk factor for diffuse-type of gastric carcinoma in Japanese young patients. Gastroenterology. 2004;126:A456.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ito, M., Takata, S., Tatsugami, M. et al. Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review. J Gastroenterol 44, 365–371 (2009). https://doi.org/10.1007/s00535-009-0036-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-009-0036-8