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Published in: Indian Journal of Gastroenterology 3/2010

01-05-2010 | Review

The enigma of Helicobacter pylori infection and gastric cancer

Authors: Uday C. Ghoshal, Rupesh Chaturvedi, Pelayo Correa

Published in: Indian Journal of Gastroenterology | Issue 3/2010

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Abstract

Although H. pylori has been recognized as a class I carcinogen, incongruence between infection prevalence and cancer incidence has been reported. Holcombe called attention to the high prevalence of infection in the face of low cancer rates, which he called “The African Enigma”. Similar observations have now been made in other geographic areas. Gastric carcinoma should be considered an infectious disease, for which the classical epidemiologic model of causality applies. The model proposes that tissue injury inflicted by the infectious agent is modulated by its interactions with host and environmental factors. Although approximately half of the world’s population is infected, only a small proportion of people develop cancer. The African enigma is a striking example of the major contrasts in cancer risk among populations with similarly high prevalence of infection. The mechanisms involved in reducing the risk of cancer in infected individuals are explored in this article, which may lead to the design of effective prevention strategies.
Literature
1.
go back to reference Warren R, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273–5. Warren R, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273–5.
3.
go back to reference Ghoshal UC, Tiwari S, Dhingra S, et al. Frequency of Helicobacter pylori and CagA antibody in patients with gastric neoplasms and controls: the Indian enigma. Dig Dis Sci. 2008;53:1215–22.CrossRefPubMed Ghoshal UC, Tiwari S, Dhingra S, et al. Frequency of Helicobacter pylori and CagA antibody in patients with gastric neoplasms and controls: the Indian enigma. Dig Dis Sci. 2008;53:1215–22.CrossRefPubMed
4.
go back to reference Achyut BR, Tripathi P, Ghoshal UC, Moorchung N, Mittal B. Interleukin-10 (-819 C/T) and tumor necrosis factor-alpha (-308 G/A) gene variants influence gastritis and lymphoid follicle development. Dig Dis Sci. 2008;53:622–9.CrossRefPubMed Achyut BR, Tripathi P, Ghoshal UC, Moorchung N, Mittal B. Interleukin-10 (-819 C/T) and tumor necrosis factor-alpha (-308 G/A) gene variants influence gastritis and lymphoid follicle development. Dig Dis Sci. 2008;53:622–9.CrossRefPubMed
5.
go back to reference Singh K, Ghoshal UC. Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol. 2006;12:1346–51.PubMed Singh K, Ghoshal UC. Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol. 2006;12:1346–51.PubMed
6.
go back to reference Goh KL, Cheah PL, Md N, Quek KF, Parasakthi N. Ethnicity and H. Pylori as risk factors for gastric cancer in malaysia: a prospective case control study. Am J Gastroenterol. 2007;102:40–5.CrossRefPubMed Goh KL, Cheah PL, Md N, Quek KF, Parasakthi N. Ethnicity and H. Pylori as risk factors for gastric cancer in malaysia: a prospective case control study. Am J Gastroenterol. 2007;102:40–5.CrossRefPubMed
7.
go back to reference Bravo LE, van Doom LJ, Realpe JL, Correa P. Virulence-associated genotypes of Helicobacter pylori: do they explain the African enigma? Am J Gastroenterol. 2002;97:2839–42.CrossRefPubMed Bravo LE, van Doom LJ, Realpe JL, Correa P. Virulence-associated genotypes of Helicobacter pylori: do they explain the African enigma? Am J Gastroenterol. 2002;97:2839–42.CrossRefPubMed
8.
go back to reference Con SA, Valerin AL, Takeuchi H, et al. Helicobacter pylori CagA status associated with gastric cancer incidence rate variability in Costa Rican regions. J Gastroenterol. 2006;41:632–7.CrossRefPubMed Con SA, Valerin AL, Takeuchi H, et al. Helicobacter pylori CagA status associated with gastric cancer incidence rate variability in Costa Rican regions. J Gastroenterol. 2006;41:632–7.CrossRefPubMed
9.
go back to reference Miwa H, Go MF, Sato N. H. pylori and gastric cancer: the Asian enigma. Am J Gastroenterol. 2002;97:1106–12.CrossRefPubMed Miwa H, Go MF, Sato N. H. pylori and gastric cancer: the Asian enigma. Am J Gastroenterol. 2002;97:1106–12.CrossRefPubMed
10.
go back to reference IARC Monographs on the evaluation of carcinogenic risks to humans. schistosomes, liver flukes and Helicobacter pylori. IARC 1994:177–240. IARC Monographs on the evaluation of carcinogenic risks to humans. schistosomes, liver flukes and Helicobacter pylori. IARC 1994:177–240.
11.
go back to reference Correa P, Haenszel W, Cuello C, et al. A model for gastric cancer epidemiology. Lancet. 1975;2:58–60.CrossRefPubMed Correa P, Haenszel W, Cuello C, et al. A model for gastric cancer epidemiology. Lancet. 1975;2:58–60.CrossRefPubMed
12.
go back to reference Achtman M, Azuma T, Berg DE, et al. Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol Microbiol. 1999;32:459–70.CrossRefPubMed Achtman M, Azuma T, Berg DE, et al. Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol Microbiol. 1999;32:459–70.CrossRefPubMed
13.
go back to reference Blaser MJ, Perez-Perez GI, Kleanthous H, et al. Infection with Helicobacter pylori strains possessing CagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55:2111–5.PubMed Blaser MJ, Perez-Perez GI, Kleanthous H, et al. Infection with Helicobacter pylori strains possessing CagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55:2111–5.PubMed
14.
go back to reference Covacci A, Censini S, Bugnoli M, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993;90:5791–5.CrossRefPubMed Covacci A, Censini S, Bugnoli M, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993;90:5791–5.CrossRefPubMed
15.
go back to reference Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science. 1999;284:1328–33.CrossRefPubMed Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science. 1999;284:1328–33.CrossRefPubMed
16.
go back to reference Azuma T, Yamakawa A, Yamazaki S, et al. Correlation between variation of the 3' region of the CagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis. 2002;186:1621–30.CrossRefPubMed Azuma T, Yamakawa A, Yamazaki S, et al. Correlation between variation of the 3' region of the CagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis. 2002;186:1621–30.CrossRefPubMed
17.
go back to reference Higashi H, Tsutsumi R, Fujita A, et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A. 2002;99:14428–33.CrossRefPubMed Higashi H, Tsutsumi R, Fujita A, et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A. 2002;99:14428–33.CrossRefPubMed
18.
go back to reference Basso D, Zambon CF, Letley DP, et al. Clinical relevance of Helicobacter pylori CagA and VacA gene polymorphisms. Gastroenterology. 2008;135:91–9.CrossRefPubMed Basso D, Zambon CF, Letley DP, et al. Clinical relevance of Helicobacter pylori CagA and VacA gene polymorphisms. Gastroenterology. 2008;135:91–9.CrossRefPubMed
19.
go back to reference Atherton JC, Cao P, Peek Jr RM, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific VacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270:17771–7.CrossRefPubMed Atherton JC, Cao P, Peek Jr RM, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific VacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270:17771–7.CrossRefPubMed
20.
go back to reference Peek Jr RM, Thompson SA, Donahue JP, et al. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians. 1998;110:531–44.PubMed Peek Jr RM, Thompson SA, Donahue JP, et al. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians. 1998;110:531–44.PubMed
21.
go back to reference Aspholm-Hurtig M, Dailide G, Lahmann M, et al. Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science. 2004;305:519–22.CrossRefPubMed Aspholm-Hurtig M, Dailide G, Lahmann M, et al. Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science. 2004;305:519–22.CrossRefPubMed
22.
go back to reference Gerhard M, Lehn N, Neumayer N, et al. Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci U S A. 1999;96:12778–83.CrossRefPubMed Gerhard M, Lehn N, Neumayer N, et al. Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci U S A. 1999;96:12778–83.CrossRefPubMed
23.
go back to reference Giannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci U S A. 2008;105:4358–63.CrossRefPubMed Giannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci U S A. 2008;105:4358–63.CrossRefPubMed
24.
go back to reference Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A. 1992;89:3030–4.CrossRefPubMed Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A. 1992;89:3030–4.CrossRefPubMed
25.
go back to reference Xu H, Chaturvedi R, Cheng Y, et al. Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res. 2004;64:8521–5.CrossRefPubMed Xu H, Chaturvedi R, Cheng Y, et al. Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res. 2004;64:8521–5.CrossRefPubMed
26.
go back to reference Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy. Nat Med. 2000;6:536–42.CrossRefPubMed Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy. Nat Med. 2000;6:536–42.CrossRefPubMed
27.
go back to reference Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006;30:45–51.CrossRefPubMed Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006;30:45–51.CrossRefPubMed
28.
go back to reference Foryst-Ludwig A, Neumann M, Schneider-Brachert W, Naumann M. Curcumin blocks NF-kappaB and the motogenic response in Helicobacter pylori-infected epithelial cells. Biochem Biophys Res Commun. 2004;316:1065–72.CrossRefPubMed Foryst-Ludwig A, Neumann M, Schneider-Brachert W, Naumann M. Curcumin blocks NF-kappaB and the motogenic response in Helicobacter pylori-infected epithelial cells. Biochem Biophys Res Commun. 2004;316:1065–72.CrossRefPubMed
29.
go back to reference Dorant E, van den Brandt PA, Goldbohm RA, Sturmans F. Consumption of onions and a reduced risk of stomach carcinoma. Gastroenterology. 1996;110:12–20.CrossRefPubMed Dorant E, van den Brandt PA, Goldbohm RA, Sturmans F. Consumption of onions and a reduced risk of stomach carcinoma. Gastroenterology. 1996;110:12–20.CrossRefPubMed
30.
go back to reference Loh JT, Torres VJ, Cover TL. Regulation of Helicobacter pylori CagA expression in response to salt. Cancer Res. 2007;67:4709–15.CrossRefPubMed Loh JT, Torres VJ, Cover TL. Regulation of Helicobacter pylori CagA expression in response to salt. Cancer Res. 2007;67:4709–15.CrossRefPubMed
31.
go back to reference Camargo MC, Mera R, Correa P, et al. Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006;15:1674–87.CrossRefPubMed Camargo MC, Mera R, Correa P, et al. Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006;15:1674–87.CrossRefPubMed
32.
go back to reference Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology. 2008;134:306–23.CrossRefPubMed Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology. 2008;134:306–23.CrossRefPubMed
33.
go back to reference Achyut BR, Ghoshal UC, Moorchung N, Mittal B. Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. Hum Immunol. 2007;68:901–7.CrossRefPubMed Achyut BR, Ghoshal UC, Moorchung N, Mittal B. Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. Hum Immunol. 2007;68:901–7.CrossRefPubMed
34.
go back to reference Achyut BR, Ghoshal UC, Moorchung N, Mittal B. Role of cyclooxygenase-2 functional gene polymorphisms in Helicobacter pylori induced gastritis and gastric atrophy. Mol Cell Biochem. 2009;321:103–9.CrossRefPubMed Achyut BR, Ghoshal UC, Moorchung N, Mittal B. Role of cyclooxygenase-2 functional gene polymorphisms in Helicobacter pylori induced gastritis and gastric atrophy. Mol Cell Biochem. 2009;321:103–9.CrossRefPubMed
35.
go back to reference Tripathi S, Ghoshal U, Ghoshal UC, et al. Gastric carcinogenesis: Possible role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes. Scand J Gastroenterol. 2008;43:431–9.CrossRefPubMed Tripathi S, Ghoshal U, Ghoshal UC, et al. Gastric carcinogenesis: Possible role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes. Scand J Gastroenterol. 2008;43:431–9.CrossRefPubMed
36.
go back to reference Ghoshal UC, Tripathi S, Ghoshal U. The Indian enigma of frequent H. pylori infection but infrequent gastric cancer: is the magic key in Indian diet, host's genetic make up, or friendly bug? Am J Gastroenterol. 2007;102:2113–4.CrossRefPubMed Ghoshal UC, Tripathi S, Ghoshal U. The Indian enigma of frequent H. pylori infection but infrequent gastric cancer: is the magic key in Indian diet, host's genetic make up, or friendly bug? Am J Gastroenterol. 2007;102:2113–4.CrossRefPubMed
37.
go back to reference Figueiredo C, Machado JC, Pharoah P, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst. 2002;94:1680–7.PubMed Figueiredo C, Machado JC, Pharoah P, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst. 2002;94:1680–7.PubMed
38.
go back to reference xKidd M, Lastovica AJ, Atherton JC, Louw JA. Heterogeneity in the Helicobacter pylori VacA and CagA genes: association with gastroduodenal disease in South Africa? Gut. 1999;45:499–502.CrossRefPubMed xKidd M, Lastovica AJ, Atherton JC, Louw JA. Heterogeneity in the Helicobacter pylori VacA and CagA genes: association with gastroduodenal disease in South Africa? Gut. 1999;45:499–502.CrossRefPubMed
39.
go back to reference Letley DP, Lastovica A, Louw JA, Hawkey CJ, Atherton JC. Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South Africa: rarity of the VacA s1a genotype and natural occurrence of an s2/m1 allele. J Clin Microbiol. 1999;37:1203–5.PubMed Letley DP, Lastovica A, Louw JA, Hawkey CJ, Atherton JC. Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South Africa: rarity of the VacA s1a genotype and natural occurrence of an s2/m1 allele. J Clin Microbiol. 1999;37:1203–5.PubMed
40.
41.
go back to reference Singh M, Prasad KN, Yachha SK, Krishnani N. Genotypes of Helicobacter pylori in children with upper abdominal pain. J Gastroenterol Hepatol. 2003;18:1018–23.CrossRefPubMed Singh M, Prasad KN, Yachha SK, Krishnani N. Genotypes of Helicobacter pylori in children with upper abdominal pain. J Gastroenterol Hepatol. 2003;18:1018–23.CrossRefPubMed
42.
go back to reference Kumar S, Dhar A, Srinivasan S, Jain S, Rattan A, Sharma MP. Antibodies to CagA protein are not predictive of serious gastroduodenal disease in Indian patients. Indian J Gastroenterol. 1998;17:126–8.PubMed Kumar S, Dhar A, Srinivasan S, Jain S, Rattan A, Sharma MP. Antibodies to CagA protein are not predictive of serious gastroduodenal disease in Indian patients. Indian J Gastroenterol. 1998;17:126–8.PubMed
43.
go back to reference Devi SM, Ahmed I, Francalacci P, et al. Ancestral European roots of Helicobacter pylori in India. BMC Genomics. 2007;8:184.CrossRefPubMed Devi SM, Ahmed I, Francalacci P, et al. Ancestral European roots of Helicobacter pylori in India. BMC Genomics. 2007;8:184.CrossRefPubMed
44.
go back to reference Correa P, Cuello C, Duque E, et al. Gastric cancer in Colombia. III. Natural history of precursor lesions. J Natl Cancer Inst. 1976;57:1027–35.PubMed Correa P, Cuello C, Duque E, et al. Gastric cancer in Colombia. III. Natural history of precursor lesions. J Natl Cancer Inst. 1976;57:1027–35.PubMed
45.
go back to reference Llanos G, Correa P. Morbilidad por cancer en Cartagena. Antioquia Medica. 1966;23:230–9. Llanos G, Correa P. Morbilidad por cancer en Cartagena. Antioquia Medica. 1966;23:230–9.
46.
go back to reference Camargo MC, Yepez MC, Ceron C, et al. Age at acquisition of Helicobacter pylori infection: comparison of two areas with contrasting risk of gastric cancer. Helicobacter. 2004;9:262–70.CrossRefPubMed Camargo MC, Yepez MC, Ceron C, et al. Age at acquisition of Helicobacter pylori infection: comparison of two areas with contrasting risk of gastric cancer. Helicobacter. 2004;9:262–70.CrossRefPubMed
47.
go back to reference Whary MT, Sundina N, Bravo LE, et al. Intestinal helminthiasis in Colombian children promotes a Th2 response to Helicobacter pylori: possible implications for gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev. 2005;14:1464–9.CrossRefPubMed Whary MT, Sundina N, Bravo LE, et al. Intestinal helminthiasis in Colombian children promotes a Th2 response to Helicobacter pylori: possible implications for gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev. 2005;14:1464–9.CrossRefPubMed
48.
go back to reference MacDonald WC, Owen DA, Le N. Chronic advanced gastric cancer: clinicopathologic analysis of survival data. Hum Pathol. 2008;39:641–9.CrossRefPubMed MacDonald WC, Owen DA, Le N. Chronic advanced gastric cancer: clinicopathologic analysis of survival data. Hum Pathol. 2008;39:641–9.CrossRefPubMed
Metadata
Title
The enigma of Helicobacter pylori infection and gastric cancer
Authors
Uday C. Ghoshal
Rupesh Chaturvedi
Pelayo Correa
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Indian Journal of Gastroenterology / Issue 3/2010
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-010-0024-1

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