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Gastric cancer: pathogenesis, risks, and prevention

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Abstract

Intestinal (IGCA) and diffuse (DGCA) gastric adenocarcinomas, the two main microscopic subtypes, are dissimilar regarding their epidemiological and demographic characteristics. Both tumor types comprise approximately 40% of all gastric adenocarcinomas. The DGCAs more often occur in young age groups, more often affect the corpus, and are less infrequently associated with atrophic gastritis and intestinal metaplasia than the IGCAs. The risk of both DGCA and IGCA is increased in the presence ofHelicobacter pylori infection, and the risk rises with increases in grade and extent of atrophic gastritis and intestinal metaplasia. It is likely that the development of up to 80% of the DGCAs and IGCAs can be prevented with early eradication of theH. pylori infection. The pathogenesis and morphogenesis of DGCAs are unknown, but the morphogenesis of IGCAs includes identifiable precancerous conditions such as atrophie gastritis and intestinal metaplasia as well as identifiable precancerous lesions (adenomas, dysplasias). Atrophic gastritis is a direct result of theH. pylori infestation. Atrophic gastritis, for unknown reasons, appears in more than half of the infected subjects during their lifetime.H. pylori gastritis triggers a variety of reactions, with the reaction cascades resulting in errors of the cell genome and ending up as neoplastic tumors.

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References

  1. Schistosomes, liver flukes andHelicobacter pylori. In: IARC Monographs on the Evaluation of Carcinogenic Risks to humans. Vol 61. Lyon: IARC, 1994. p. 177–220.

  2. Correa P. The epidemiology and pathogenesis of chronic gastritis: three etiologic entities. Front Gastrointest Res 1980;6:98–108.

    PubMed  CAS  Google Scholar 

  3. Correa P. Human gastric carcinogenesis: multistep and multifactorial process. Cancer Res 1992;52:6735–40.

    PubMed  CAS  Google Scholar 

  4. Howson CP, Hiyama T, Wynder EL. The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev 1986;8:l-27.

    Google Scholar 

  5. Siurala M, Sipponen P, Kekki M. Chronic gastritis: dynamic and clinical aspects. Scand J Gastroenterol 1985;20(suppl 109):69–76.

    Article  Google Scholar 

  6. Ihamäki T, Varis K, Siurala M. Morphological, functional and immunological state of the gastric mucosa in gastric carcinoma families: comparison with a computer-matched family sample. Scand J Gastroenterol 1979;14:801–12.

    Article  PubMed  Google Scholar 

  7. Niemelä S, Karttunen T, Kerola T.Helicobacter pylori-associated gastritis: evolution of histological changes over 10 years. Scand J Gastroenterol 1995;30:542–9.

    Article  PubMed  Google Scholar 

  8. Valle J, Kekki M, Sipponen P, Ihamäki T, Siurala M. Long-term course and consequences ofHelicobacter pylori gastritis: results of a 32-year follow-up study. Scand J Gastroenterol 1996;31:546–50.

    Article  PubMed  CAS  Google Scholar 

  9. Ihamäki T, Kekki M, Sipponen P, Siurala M. The sequelae and course of chronic gastritis during a period a 30–34 years bioptical follow-up. Scand J Gastroenterol 1985;20:485–91.

    Article  PubMed  Google Scholar 

  10. Louhija J, Rehnberg-Laiho L, Rautelin H, Jusofovic J, Tilvis R, Miettinen A, et al.Helicobacter antibodies, parietal cell antibodies and s-pepsinogen I concentration in Finnish centenarians. Scand J Gastroenterol 1999;34(suppl 229):9(A32).

    Google Scholar 

  11. Correa P, Shiao Y-H. Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res 1994;54:1941–3.

    Google Scholar 

  12. Correa P. Chronic gastritis and gastric cancer. In: Ming SC, editor. Precursor of gastric cancer. New York: Praeger, 1984. p. 105–16.

    Google Scholar 

  13. You WC, Zhang L, Gail MH, Ma JL, Chang YS, Blot WJ, et al.Helicobacter pylori infection, garlic intake and precancerous lesions in a Chinese population at low risk of gastric cancer. Int J Epidemiol 1998;27:941–4.

    Article  PubMed  CAS  Google Scholar 

  14. Azuma T, Ito S, Sato F, Yamazaki Y, Miyaji H, Ito Y, et al. The role of the HLA-DQA1 gene in resistance to atrophic gastritis and gastric adenocarcinoma induced byHelicobacter pylori infection. Cancer 1998;82:1013–8.

    Article  PubMed  CAS  Google Scholar 

  15. Sipponen P, Kekki M, Siurala M. Precancerous conditions. In: Filipe MI, Jass JR, editors. Gastric cancer: current problems in tumour pathology. London: Churchill Livingstone, 1985. p. 152–71.

    Google Scholar 

  16. O’Connor HJ. Helicobacter pylori and gastric cancer: a review and hypothesis. Eur J Gastroenterol Hepatol 1992;4:103–9.

    Google Scholar 

  17. Morson BC, Sobin LH, Grundmann E, Johansen AA, Nagayo T, Serck-Hanssen A. Precancerous conditions and epithelial dysplasia in the stomach. J Clin Pathol 1980;33:711–21.

    Article  PubMed  CAS  Google Scholar 

  18. Varis K, Taylor PR, Sipponen P, Samloff IM, Heinonen OP, Albanes D, et al. Gastric cancer and premalignant lesions in atrophie gastritis: a controlled trial on the effect of supplementation with alpha-tocopherol and beta-carotene. Scand J Gastroenterol 1998;33:294–300.

    Article  PubMed  CAS  Google Scholar 

  19. Jass JR, Filipe MI. The mucin profiles of normal gastric mucosa, intestinal metaplasia and its variants and gastric carcinoma. Histochem J 1981;13:931–9.

    Article  PubMed  CAS  Google Scholar 

  20. Johansen A. Early gastric cancer: a contribution to the pathology and to cancer histogenesis. Dissertation, Department of Pathology, Bispebjaerg Hospital, Copenhagen, 1981.

  21. Terres AM, Pajares JM, O’Toole D, Ahern S, Kelleher D.H. pylori infection is associated with downregulation of E-cadherin, a molecule involved in epithelial cell adhesion and proliferation control. J Clin Pathol 1998;51:410–2.

    Article  PubMed  CAS  Google Scholar 

  22. Tahara E. Molecular biology of gastric cancer. World J Surg 1995;19:484–90.

    Article  PubMed  CAS  Google Scholar 

  23. Sipponen P, Hyvärinen H, Seppälä K, Blaser MJ. Review article: pathogenesis of the transformation from gastritis to malignancy. Aliment Pharmacol Ther 1998;12(suppl 1):61–71.

    Article  PubMed  CAS  Google Scholar 

  24. Palli D, Cipriani F, Decarli A, Galli M, Saieva C, Fraumeni JF, et al. Reproductive history and gastric cancer among postmenopausal women. Int Jurol Cancer 1994;56:812–5.

    Article  CAS  Google Scholar 

  25. Sipponen P, Kekki M, Haapakoski J, Ihamäki T, Siurala M. Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data. Int J Cancer 1985;35:173–7.

    Article  PubMed  CAS  Google Scholar 

  26. Varis K. Surveillance of pernicious anaemia. In: Sherlock P, Morson BC, Barbara L, Veronesi V, editors. Precancerous lesions of the gastrointestinal tract. New York: Raven Press, 1983. p. 189–94.

    Google Scholar 

  27. Sjöblom S-M, Sipponen P, Miettinen M, Karonen S-L, Järvinen HJ. Gastroscopic screening for gastric carcinoids and carcinoma in pernicious anaemia. Endoscopy 1988;20:52–6.

    Article  PubMed  Google Scholar 

  28. Tahara E. Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol 1993;119:265–72.

    Article  PubMed  CAS  Google Scholar 

  29. Dohi T, Hashiguchi M, Yamamoto S, Morita H, Oshima M. Fucosyltransferase-producing sialyl Le(a) and sialyl Le(x) carbohydrate antigen in benign and malignant gastrointestinal mucosa. Cancer 1994;73:1552–61.

    Article  PubMed  CAS  Google Scholar 

  30. Kobayashi K, Sakemoto J, Kito T, Yamamura Y, Koskokawa T, Fujita M, et al. Lewis blood group-related antigen expression in normal gastric epithelium, intestinal metaplasia, gastric adenoma, and gastric carcinoma. Am J Gastroenterol 1993;88:919–24.

    PubMed  CAS  Google Scholar 

  31. Torrado J, Correa P, Ruiz B, Bernardi P, Zavala D, Bara J. Lewis antigen alterations in gastric cancer precursors. Gastroenterology 1992;102:424–30.

    PubMed  CAS  Google Scholar 

  32. Torrado J, Correa P, Ruiz B, Zavala D, Bara J. Prospective study of Lewis antigen alterations in the gastric precancerous process. Cancer Epidemiol Biomarkers Prev 1992;1:199–205.

    PubMed  CAS  Google Scholar 

  33. Torrado J, Blasco E, Gutierrez-Hoyos A, Cosme A, Lojendio M, Arenas JI. Lewis system alteration in gastric carcinogenesis. Cancer 1990;66:1769–74.

    Article  PubMed  CAS  Google Scholar 

  34. Sipponen P, Äärynen M, Kääriäinen I, Kettunen P, Helske T, Seppälä K. Chronic antral gastritis, Lewis(a+) phenotype, and male sex as factors in predicting coexisting duodenal ulcer. Scand J Gastroenterol 1989;24:581–8.

    Article  PubMed  CAS  Google Scholar 

  35. Murata K, Egami H, Shibata Y, Sakamoto K, Misumi A, Ogawa M. Expression of blood group related antigens, ABH, Lewis(a), Lewis(b), Lewis(x), Lewis(y), Cal9-9, and CSLEX1 in early cancer, intestinal metaplasia, and uninvolved mucosa of the stomach. Am J Clin Pathol 1992;98:67–75.

    PubMed  CAS  Google Scholar 

  36. Sipponen P, Lindren J. Sialylated Lewisa determinant CA 19-9 in benign and malignant gastric tissue. Acta Pathol Microbiol Immunol Scand A 1986;94:305–11.

    PubMed  CAS  Google Scholar 

  37. Tahara E, Kuniyasu H, Yasui W, Yokozaki H. Gene alterations in intestinal metaplasia and gastric cancer. Eur J Gastroenterol Hepatol 1994;6(suppl l):S97–101.

    PubMed  Google Scholar 

  38. Freston JW.Helicobacter pylori, acid, gastritis, atrophy and progression to cancer: a critical view. In: Hunt RH, Tytgat GNJ, editors.Helicobacter pylori: basic mechanisms to clinical cure 1996. Dordrecht: Kluwer, 1996. p. 245–54.

    Google Scholar 

  39. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process: first American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res. 1992;52:6735–40.

    PubMed  CAS  Google Scholar 

  40. Tamura G, Kihana T, Nomura K, Terada M, Hirohashi S. Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-stranded conformation polymorphism analysis. Cancer Res 1991;51:3056–8.

    PubMed  CAS  Google Scholar 

  41. Strickler JG, Zheng J, Shu Q, Burgart LJ, Alberts SR, Shibata D. p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail. Cancer Res 1994;54:4750–5.

    PubMed  CAS  Google Scholar 

  42. Ranzani GN, Luinetti O, Padovan LS, CValistri D, Renault B, Murrel M, et al. p53 mutations and protein nuclear accumulation are early events in intestinal type gastric cancer but late events in diffuse type. Cancer Epidemiol Biomarkers Prev 1995;4:223–31.

    PubMed  CAS  Google Scholar 

  43. Rhyu M-G, Park W-S, Jung Y-J, Choi S-W, Meltzer SJ. Allelic deletion of MCC/APC and p53 are frequent late events in human gastric carcinogenesis. Gastroenterology 1994;106:1584–8.

    PubMed  CAS  Google Scholar 

  44. Correa P, Shiao Y-H. Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res 1994;54:1941s-3s.

    PubMed  CAS  Google Scholar 

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  1. Department of Pathology, Jorvi Hospital, 02740, Espoo, Finland

    Pentti Sipponen

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Sipponen, P. Gastric cancer: pathogenesis, risks, and prevention. J Gastroenterol 37 (Suppl 13), 39–44 (2002). https://doi.org/10.1007/BF02990098

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