Skip to main content

Advertisement

SpringerLink
Log in

The Risk of Gastric Cancer in Patients with Duodenal and Gastric Ulcer: Research Progresses and Clinical Implications

  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Introduction

Although controversial, clinicians generally consider patients who present with gastric ulcer to have an increased risk of gastric cancer, while the risk for patients with duodenal ulcer is reduced in comparison with that of the general population. Infection with Helicobacter pylori and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are the major causes for peptic ulcers, but their roles in relation to the risk of gastric cancer in patients with peptic ulcer may be different.

Methods and Results

This article reviewed existing literature to assess our understanding of the risk of gastric cancer in patients with gastric and duodenal ulcers more than 25 years after the discovery of H. pylori and also examined whether gastric ulcers induced by NSAID carry a lower risk of gastric cancer as compared to those induced by H. pylori infection or other causes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311–5.

    Article  PubMed  CAS  Google Scholar 

  2. Konturek SJ, Konturek PC, Brzozowski T, et al. From nerves and hormones to bacteria in the stomach; Nobel prize for achievements in gastrology during last century. J Physiol Pharmacol 2005;56:507–30.

    PubMed  CAS  Google Scholar 

  3. Egan BJ, O’Morain CA. A historical perspective of Helicobacter gastroduodenitis and its complications. Best Pract Res Clin Gastroenterol 2007;21:335–46.

    Article  PubMed  Google Scholar 

  4. Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 2000;54:615–40.

    Article  PubMed  CAS  Google Scholar 

  5. Zhang ZW, Reynolds JV. The risk of gastric cancer in patients with gastric and duodenal ulcer. CML Gastroenterology 2005;24:45–9.

    Google Scholar 

  6. Hansson LE. Risk of stomach cancer in patients with peptic ulcer disease. World J Surg 2000;24:315–20.

    Article  PubMed  CAS  Google Scholar 

  7. Hansson LE, Nyren O, Hsing AW, et al. The risk of stomach cancer in patients with gastric or duodenal ulcer disease. N Engl J Med 1996;335:242–9.

    Article  PubMed  CAS  Google Scholar 

  8. Lewis JH, Woods M 3rd. Gastric carcinoma in patients with unoperated duodenal ulcer disease. Am J Gastroenterol 1982;77:368–73.

    PubMed  CAS  Google Scholar 

  9. Norfleet RG, Johnson SE. Strange bedfellows: duodenal ulcer and cancer of the stomach. J Clin Gastroenterol 1989;11:382–5.

    Article  PubMed  CAS  Google Scholar 

  10. Meister H, Holubarsch C, Haferkamp O, et al. Gastritis, intestinal metaplasia and dysplasia versus benign ulcer in stomach and duodenum and gastric carcinoma—a histotopographical study. Pathol Res Pract 1979;164:259–69.

    PubMed  CAS  Google Scholar 

  11. Sipponen P. Update on the pathologic approach to the diagnosis of gastritis, gastric atrophy, and Helicobacter pylori and its sequelae. J Clin Gastroenterol 2001;32:196–202.

    Article  PubMed  CAS  Google Scholar 

  12. Molloy RM, Sonnenberg A. Relation between gastric cancer and previous peptic ulcer disease. Gut 1997;40:247–52.

    PubMed  CAS  Google Scholar 

  13. Wang WH, Huang JQ, Zheng GF, et al. Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst 2003;95:1784–91.

    PubMed  CAS  Google Scholar 

  14. Dai Y, Wang WH. Non-steroidal anti-inflammatory drugs in prevention of gastric cancer. World J Gastroenterol 2006;12:2884–9.

    PubMed  CAS  Google Scholar 

  15. Yamagata S, Hisamichi S. Precancerous lesions of the stomach. World J Surg 1979;3:671–3.

    Article  PubMed  CAS  Google Scholar 

  16. Lee S, Iida M, Yao T, et al. Long-term follow-up of 2529 patients reveals gastric ulcers rarely become malignant. Dig Dis Sci 1990;35:763–8.

    Article  PubMed  CAS  Google Scholar 

  17. Thomopoulos KC, Melachrinou MP, Mimidis KP, et al. Gastric ulcers and risk for cancer. Is follow-up necessary for all gastric ulcers? Int J Clin Pract 2004;58:675–7.

    Article  PubMed  CAS  Google Scholar 

  18. Wong J, Ong GB. Gastric carcinoma developing in chronic gastric ulcer in the rat treated with N-methyl-N1-nitro-N-nitrosoguanidine. J Surg Res 1980;29:446–50.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Lee S, Iida M, Yao T, et al. Risk of gastric cancer in patients with non-surgically treated peptic ulcer. Scand J Gastroenterol 1990;25:1223–6.

    Article  PubMed  CAS  Google Scholar 

  21. Krause U. Long term results of medical and surgical treatment of peptic ulcer: a follow-up investigation of patients initially treated conservatively between 1925–1934. Acta Chir Scand 1963;310:1–12.

    Google Scholar 

  22. Hirohata T. Mortality from gastric cancer and other causes after medical or surgical treatment for gastric ulcer. J Natl Cancer Inst 1968;41:895–908.

    PubMed  CAS  Google Scholar 

  23. Hole DJ, Quigley EM, Gillis CR, et al. Peptic ulcer and cancer: an examination of the relationship between chronic peptic ulcer and gastric carcinoma. Scand J Gastroenterol 1987;22:17–23.

    Article  PubMed  CAS  Google Scholar 

  24. Correa P, Schmidt BA. The relationship between gastric cancer frequency and the ratio of gastric to duodenal ulcer. Aliment Pharmacol Ther 1995;9(Suppl 2):13–9.

    PubMed  Google Scholar 

  25. Johnson D. Gastric ulcer: classification, blood group characteristics and pathogenesis. Ann Surg 1965;162:996–1004.

    Article  PubMed  CAS  Google Scholar 

  26. Kawashima T. Epidemiological study on the risk of gastric cancer in patients with duodenal ulcer. Nippon Shokakibyo Gakkai Zasshi 1991;88:1161–7.

    PubMed  CAS  Google Scholar 

  27. Marshall BJ. Helicobacter pylori. Am J Gastroenterol 1994;89(8 Suppl):S116–S28.

    PubMed  CAS  Google Scholar 

  28. Zhang ZW, Newcomb P, Hollowood A, et al. A comparison study of gastric cancer risk in patients with duodenal and gastric ulcer: roles of gastric mucosal histology and p53 codon 72 polymorphism. Dig Dis Sci 2004;49:254–9.

    Article  PubMed  CAS  Google Scholar 

  29. Stemmermann GN. Intestinal metaplasia of the stomach: A status report. Cancer 1994;74:556–64.

    Article  PubMed  CAS  Google Scholar 

  30. Nomura A, Stemmermann GN, Chyou PH, et al. Helicobacter pylori infection and the risk for duodenal and gastric ulceration. Ann Intern Med 1994;120:977–81.

    PubMed  CAS  Google Scholar 

  31. Calam J, Baron JH. ABC of the upper gastrointestinal tract: Pathophysiology of duodenal and gastric ulcer and gastric cancer. BMJ 2001;323:980–2.

    Article  PubMed  CAS  Google Scholar 

  32. Schoenfeld P, Kimmey MB, Scheiman J, et al. Review article: nonsteroidal anti-inflammatory drug-associated gastrointestinal complications—guidelines for prevention and treatment. Aliment Pharmacol Ther 1999;13:1273–85.

    Article  PubMed  CAS  Google Scholar 

  33. Laine L. GI risk and risk factors of NSAIDs. J Cardiovasc Pharmacol 2006;47(Suppl 1):S60–S6.

    Article  PubMed  CAS  Google Scholar 

  34. Hawkey C, Laine L, Simon T, et al. Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group. Arthritis Rheum 2000;43:370–7.

    Article  PubMed  CAS  Google Scholar 

  35. Laine L. Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology 2001;120:594–606.

    Article  PubMed  CAS  Google Scholar 

  36. Simon LS. Risk factors and current NSAID use. J Rheumatol 1999;26:1429–31.

    PubMed  CAS  Google Scholar 

  37. Graham DY, Smith JL. Aspirin and the stomach. Ann Intern Med 1986;104:390–8.

    PubMed  CAS  Google Scholar 

  38. Konturek PC. Physiological, immunohistochemical and molecular aspects of gastric adaptation to stress, aspirin and to H. pylori-derived gastrotoxins. J Physiol Pharmacol 1997;48:3–42.

    PubMed  CAS  Google Scholar 

  39. Berkowitz JM, Rogenes PR, Sharp JT, et al. Ranitidine protects against gastroduodenal mucosal damage associated with chronic aspirin therapy. Arch Intern Med 1987;147:2137–9.

    Article  PubMed  CAS  Google Scholar 

  40. Voutilainen M, Sokka T, Juhola M, et al. Nonsteroidal anti-inflammatory drug-associated upper gastrointestinal lesions in rheumatoid arthritis patients. Relationships to gastric histology, Helicobacter pylori infection, and other risk factors for peptic ulcer. Scand J Gastroenterol 1998;33:811–6.

    Article  PubMed  CAS  Google Scholar 

  41. Al-Assi MT, Genta RM, Karttunen TJ, et al. Ulcer site and complications: relation to Helicobacter pylori infection and NSAID use. Endoscopy 1996;28:229–33.

    PubMed  CAS  Google Scholar 

  42. Kyrtopoulos SA. N-nitroso compound formation in human gastric juice. Cancer Surv 1989;8:423–42.

    PubMed  CAS  Google Scholar 

  43. You WC, Zhang L, Yang CS, et al. Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions. Cancer Epidemiol Biomark Prev 1996;5:47–52.

    CAS  Google Scholar 

  44. Joossens JV, Hill MJ, Elliott P, et al. Dietary salt, nitrate and stomach cancer mortality in 24 countries. European Cancer Prevention (ECP) and the INTERSALT Cooperative Research Group. Int J Epidemiol 1996;25:494–504.

    Article  PubMed  CAS  Google Scholar 

  45. Eisenbrand G, Adam B, Peter M, et al. Formation of nitrite in gastric juice of patients with various gastric disorders after ingestion of a standard dose of nitrate—a possible risk factor in gastric carcinogenesis. IARC Sci Publ 1984;57:963–8.

    PubMed  Google Scholar 

  46. Dykhuizen RS, Fraser A, McKenzie H, et al. Helicobacter pylori is killed by nitrite under acidic conditions. Gut 1998;42:334–7.

    PubMed  CAS  Google Scholar 

  47. Ziebarth D, Spiegelhalder B, Bartsch H. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori. Carcinogenesis 1997;18:383–9.

    Article  PubMed  CAS  Google Scholar 

  48. Schorah CJ, Sobala GM, Sanderson M, et al. Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis. Am J Clin Nutr 1991;53:287S–93S.

    PubMed  CAS  Google Scholar 

  49. Zhang ZW, Patchett SE, Perrett D, et al. The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach. Gut 1998;43:322–6.

    PubMed  CAS  Google Scholar 

  50. Rood JC, Ruiz B, Fontham ET, et al. Helicobacter pylori-associated gastritis and the ascorbic acid concentration in gastric juice. Nutr Cancer 1994;22:65–72.

    PubMed  CAS  Google Scholar 

  51. Poydock ME. Effect of combined ascorbic acid and B-12 on survival of mice with implanted Ehrlich carcinoma and L1210 leukemia. Am J Clin Nutr 1991;54:1261S–5S.

    PubMed  CAS  Google Scholar 

  52. Bateman DN, Colin-Jones D, Hartz S, et al. Mortality study of 18 000 patients treated with omeprazole. Gut 2003;52:942–6.

    Article  PubMed  CAS  Google Scholar 

  53. MacDonald WC, Owen DA. Gastric carcinoma after surgical treatment of peptic ulcer: an analysis of morphologic features and a comparison with cancer in the nonoperated stomach. Cancer 2001;91:1732–8.

    Article  PubMed  CAS  Google Scholar 

  54. Jensen RT. Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. Basic Clin Pharmacol Toxicol 2006;98:4–19.

    Article  PubMed  CAS  Google Scholar 

  55. Laine L, Ahnen D, McClain C, et al. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther 2000;14:651–68.

    Article  PubMed  CAS  Google Scholar 

  56. Kuipers EJ. Proton pump inhibitors and gastric neoplasia. Gut 2006;55:1217–21.

    Article  PubMed  CAS  Google Scholar 

  57. Weinstein WM. Proton pump inhibitors and H. pylori infection: why the concern? Curr Gastroenterol Rep 1999;1:507–10.

    Article  PubMed  CAS  Google Scholar 

  58. Larkin CJ, Watson RGP, Sloan JM, et al. Distribution of atrophy in Helicobacter pylori-infected subjects taking proton pump inhibitors. Scand J Gastroenterol 2000;35:578–82.

    Article  PubMed  CAS  Google Scholar 

  59. Eissele R, Brunner G, Simon B, et al. Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia. Gastroenterology 1997;112:707–17.

    Article  PubMed  CAS  Google Scholar 

  60. Klinkenberg-Knol EC, Nelis F, Dent J, et al. Long-Term Study Group. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa. Gastroenterology 2000;118:661–9.

    Article  PubMed  CAS  Google Scholar 

  61. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med 1996;334:1018–22.

    Article  PubMed  CAS  Google Scholar 

  62. Bevan S, Houlston RS. Genetic predisposition to gastric cancer. QJM 1999;92:5–10.

    Article  PubMed  CAS  Google Scholar 

  63. Aird I, Bentall HH, Mehigan JA, et al. The blood groups in relation to peptic ulceration and carcinoma of colon, rectum, breast, and bronchus—an association between the ABO groups and peptic ulceration. BMJ 1954;2:320–1.

    Google Scholar 

  64. Rotter JI. Principles and practice of medical genetics. In: Emery AE, Rimoin DL, editors. New York, NY, USA: Churchill Livingstone; 1983. p.863–78.

  65. Mentis A, Blackwell CC, Weir DM, et al. ABO blood group, secretor status and detection of Helicobacter pylori among patients with gastric or duodenal ulcers. Epidemiol Infect 1991;106:221–9.

    Article  PubMed  CAS  Google Scholar 

  66. Hallstone AE, Perez EA. Blood type and the risk of gastric disease. Science 1994;264:1386–8.

    PubMed  CAS  Google Scholar 

  67. Aird I, Bentall HH, Roberts JA. A relationship between cancer of stomach and the ABO blood groups. BMJ 1953;1:799–801.

    CAS  PubMed  Google Scholar 

  68. Boren T, Falk P, Roth KA, et al. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 1993;262:1892–5.

    Article  PubMed  CAS  Google Scholar 

  69. Zhang ZW, Dorrell N, Wren BW, et al. Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes. J Med Microbiol 2002;51:495–502.

    PubMed  CAS  Google Scholar 

  70. Buchman VL, Chumakov PM, Ninkina NN, et al. A variation in the structure of the protein-coding region of the human p53 gene. Gene 1988;70:245–52.

    Article  PubMed  CAS  Google Scholar 

  71. Matlashewski GJ, Tuck S, Pim D, et al. Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol 1987;7:961–3.

    PubMed  CAS  Google Scholar 

  72. Zhang ZW, Newcomb P, Hollowood A, et al. Age-associated increase of codon 72 arginine p53 frequency in gastric cardia and non-cardia adenocarcinoma. Clin Cancer Res 2003;9:2151–6.

    PubMed  CAS  Google Scholar 

  73. Wang YC, Chen CY, Chen SK, et al. p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis. Clin Cancer Res 1999;5:129–34.

    PubMed  CAS  Google Scholar 

  74. Kawajiri K, Nakachi K, Imai K, et al. Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis 1993;14:1085–9.

    Article  PubMed  CAS  Google Scholar 

  75. Murata M, Tagawa M, Kimura M, et al. Analysis of a germ line polymorphism of the p53 gene in lung cancer patients; discrete results with smoking history. Carcinogenesis 1996;17:261–4.

    Article  PubMed  CAS  Google Scholar 

  76. Sakagami T, Dixon M, O’Rourke J, et al. Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis. Gut 1996;39:639–48.

    Article  PubMed  CAS  Google Scholar 

  77. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest 2007;117:60–9.

    Article  PubMed  CAS  Google Scholar 

  78. iurala M, Isokoski M, Varis K, et al. Prevalence of gastritis in a rural population. Bioptic study of subjects selected at random. Scand J Gastroenterol 1968;3:211–23.

    Article  Google Scholar 

  79. Grosch S, Maier TJ, Schiffmann S, et al. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst 2006;98:736–47.

    Article  PubMed  CAS  Google Scholar 

  80. Thun MJ, Namboodiri MM, Calle EE, et al. Aspirin use and risk of fatal cancer. Cancer Res 1993;53:1322–7.

    PubMed  CAS  Google Scholar 

  81. Coogan PF, Rosenberg L, Palmer JR, et al. Nonsteroidal anti-inflammatory drugs and risk of digestive cancers at sites other than the large bowel. Cancer Epidemiol Biomark Prev 2000;9:119–23.

    CAS  Google Scholar 

  82. Farrow DC, Vaughan TL, Hansten PD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomark Prev 1998;7:97–102.

    CAS  Google Scholar 

  83. Bustamante M, Devesa F, Borghol A, et al. Accuracy of the initial endoscopic diagnosis in the discrimination of gastric ulcers: is endoscopic follow-up study always needed? J Clin Gastroenterol 2002;35:25–8.

    Article  PubMed  Google Scholar 

  84. Hopper AN, Stephens MR, Lewis WG, et al. Relative value of repeat gastric ulcer surveillance gastroscopy in diagnosing gastric cancer. Gastric Cancer 2006;9:217–22.

    Article  PubMed  Google Scholar 

  85. Hosokawa O, Watanabe K, Hatorri M, et al. Detection of gastric cancer by repeat endoscopy within a short time after negative examination. Endoscopy 2001;33:301–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Norfolk and Norwich University Hospital, University of East Anglia, Colney Lane, Norwich, NR4 7UY, UK

    Zunwu Zhang

Authors
  1. Zunwu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zunwu Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Z. The Risk of Gastric Cancer in Patients with Duodenal and Gastric Ulcer: Research Progresses and Clinical Implications. J Gastrointest Canc 38, 38–45 (2007). https://doi.org/10.1007/s12029-008-9015-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-008-9015-1

Keywords

Search

Navigation