- Email: [email protected]
Nonspecific but prognostic Helicobacter pylori and gastric cancer association
Biomed & Pharmacother 2000 ; 54 : 359-61 0 2000 editions scientifiques et mkdicales Elsevier
SAS. All rights reserved
Editorial
Nonspecific but prognostic Helicobacter and gastric cancer association
pylori
G. Math6 Institut
Helicobacterpylori
/ gastritis
de Canc&ologie
/ gastric
et d’hmunologie & Hapita 92133 Issy-les-Mouheaux
dysplasia
I gastric
Suisse de Paris, BP 60, 6-10, cedex, France
rue Minard,
cancer
Helicobacterpylori (HP) has been discovered as a factor associated not only to gastric cancer (GC) at its neoplastic phase, but to all tumoral or pretumor phases, metastatis, dysplastic and even gastritic [ 11.This added bacteria to viruses and parasites in cancer epidemiology. It was not, however, simplifying the concept of the microorganism role in cancer pathogenesis: contrary to the usually specific and direct action of viruses, its role appeared to belong to nonspecific factors such as inflammation. In fact, the correlation between this bacteria’s presence and pre-cancer dysplasia is more frequent than that with established tumors. When the correlation of global HP and GC incidence is indeed replaced by those of GC stratified according to tumor stages and patients’ ages, it appears that the frequency of this bacterial presence is not only more often correlated with precancerous conditions than with established tumors, but that it is found more in young than in aged patients [ 1, 21. Haruma et al. [1], who published such results, considered that the role of HP was only situated at the level of gastritis, and that its presence essentially predicted the cancer risk of a gastritis. More interesting, HP incidences in the different gastric and pathologic conditions are not 100% [3]. All authors today have not only recognized that HP is found in several other types of gastric pathology than cancer, but even in peptic ulcer [4], gastroduodenal[5], enterogastric reflux [3,5], and even in intestinal gastric metaplasia [6,7]. Still more interesting and important is its lack of specificity as far as the type of cancer is concerned. It can be associated with adenocarcinoma, which suggests
its effect on gastric epithelium; it may also be associated with mucosa-associated lymphoid tissue (MALT) tumors, which are lymphomas [S, 91. Interestingly in this last case, it had first been considered that HP was most often associated with lowgrade B cell lymphoma. It was possibly associated to the t (11, 18) (q21, q 21) translocation type which results in c-IAP2-MALT l/MLT gene alteration [9]. Nakamura [9] distinguishes this ‘polypoid’ type of MALT-C lesion, from the forms he calls CR (MALTA), PR (MALT B) and NC (MALT-C), identified on the basis of their reactions to eradication of HP. But in fact, it can also be associated with high-grade MALT lymphoma [lo]. Some genes appear also to be important factors: thus the tag E and vat A S 1 genotypes are more prevalent in patients with gastric cancer than other genotypes. They are also prevalent in peptic ulcer [l I]. Statistics are complicated by the fact that it is sometimes impossible to distinguish lymphoid hyperplasias from lymphomas: clonal B-cell populations may be present in both reactive and neoplastic MALT tissues [ll, 121. In fact, HP is associated with several types of lesions, not only from lymphocytes (CD20, CD45, CD45RO) [I I], but from epithelial cells; metaplastic, as well as dysplastic and neoplastic epithelial clones have been observed [ 121. Not only can it affect lymphoid and epithelial cells, it can affect both simultaneously, inducing lymphoepithelial lesions [ 1 I]. It does not affect only the mucosal and lymphoid tissues; it can also affect the stroma, and be associated with fibroid polyps [ 131.
360
G. Math6
HP does not represent a specific risk of GC. It is accused of representing not only gastroduodenal lesions, but other organ attacks such as on the salivary glands [ 141. The question of HP genetics is also important. Patients with antibodies against lower-molecularweight proteins of HP, such as those of 19.5 and 26.5 kDa, could be at greatest risk [ 151. On the other hand, the effect of HP on adhesion molecules is important as well: coculture with HP induces an increase in luciferase activity in cells which transfers with a luciferase gene linked to the 5’-flanking region of the ICAM- 1 gene [ 161. Thus HP directly induces expression of ICAMon gastric epithelial cells, in an NF-kappa-dependant manner that may support leukocyte attachment during inflammation. Cytokines such as the interleukin- 1 gene cluster polymorphism suspected of enhancing production of IL1 -b are associated with hypochloremia induced by HP and with gastric cancer [ 171. The treatment would be less efficient in case of less virulent genotypes of HP [ 181. One of the most informative facts about the role of HP which still may be at this point associated, by chance or by interaction, is the effect of bacterial treatment. The most efficient combines ranitidine, bismuth citrate, and two antibodies: (such as clarithromycin and amoxicillin) for 10 to 14 days: the eradication rate is on the order of 80% [ 19,201. Omeprazole may replace ranitidine [21]. HZblockers have to be applied long-term
Ea. Does HP eradication induce regression, remission and/or cure? That is the question indeed. The answer is yes in case of low grade MALT + [23-271. Still more interesting is prevention [28]. Unfortunately the literature is confused. It seems that HP is more active on precancerous than on cancerous lesions
WI. REFERENCES Haruma K, Komoto K, Kamada T, Ito M, Kttadai Y, Yoshihara M, et al. Helicobucterpylori infection is a major risk factor for gastric carcinoma in young pattents. Stand J Gastroenterol 2000 ; 35 : 255-9. Kath R, Fiehler J, Schneider CP, Hoffken K. Gastric cancer in very young adults: apropos four patients and a review of the literature. J Cancer Res Clm Oncol2000 ; 126 : 233-7. Fallone CA, Barkun AN, Gottke MU, Best LM, Loo VG, Veldhuyzen van Zanten S, et al. Assoctatton of Helicobucter pylon genotype with gastroesophageal reflux disease and other’upper gastrointestinal diseases. Am J Gastroenteroi 2000 ,95 659-69. Hansson LE. Risk of stomach cancer in patients with peptic ulcer disease. World J Surg 2000 ; 24 : 3 15.20.
5 Von Holstein CS. Long-term prognosis after partial gastrectomy for gastroduodenal ulcer. World J Surg 2000 ; 24 : 307-14. 6 Xia HH, Kalantar JS, Talley NJ, Wyatt JM, Adams S, Chueng K, et al. Antral-type mucosa m the gastric incisura, body, and fundus (antralization): a lurk between Helicobacter pylori infection and intestinal metaplasia? Am J of Gastroenterol2000 : 95 : 114-21. pylon gastritis in 7 Smith VC, Genta RM. Role of Helicobacter gastrtc atrophy, intestinal metaplasia, and gastric neoplasia. Microsc Res Tech 2000 ,48 : 313-20. B-cell 8 Pinottt G, Chmi C, Capella C. Most gastric low-grade lymphomas of mucosa-assoctated lymphoid tissue persist after Helicobacter pylori eradication Ann Intern Med 2000 , 132 : 846. T, Nakamura S, Yonezumt M, Suzuki T, Mat9 Nakamura suura A, Yatabe Y, et al. Helicobacter pvlori and the t (1 I, 18) (q21; q21) translocatton m gastric low-grade B-cell lymphoma of mucosa-associated lymphotd tissue type. Jpn J Cancer Res 2000 ; 91 : 301-9 10 Boot H, de Jong D, van Heerde P, Taal B. Role of Helicobacter eradtcatton m high grade MALT iymphoma. Lancet 1995 ; 346 : 448-9. 11 Saxena A, Moshynska 0, Kanthan R, Bhutan1 M, Maksymurk AW, Lukie BE. Distinct B-cell clonal bands m Helicobucterpylori gastritis wtth lymphoid hyperplasia. J Pathology 2000 ; 190 : 47-54. 12 Testino G, Comaggia M, Testino R, Valentini M. The phystopathological aspects of chronic gastritis, Helicobacferpylori and precancerous gastrtc changes. Recenti Prog Med 2000 ; 91 : 186-90. 13 Shalom A, Wasserman I. Segal M. Orda R Inflammatory fibroid polyp and Helicobacter pylori. Aetiology or coincidence? Em J Surg 2000 , 166 54-7. 14 Dev DE. Eradication de H. p?lori contre MALT salivatre. Lancet 1996 ; XX : 268-9. 15 Shtesh SC, Sheu B.S. Yang HB. Tsao HJ, Lin XZ. Serologic response to lower-molecular-wetght proteins of H. pylon 1s related to cluucal outcome of H. p~lori mfectton in Taiwan. Dig Dts Sci 2000 ; 45 781-8. 16 Infect Immun 2000 : 68 : 1806- 14. EM, Carrtngton M. Chow WH, MC Coil KE, 17 El-Omar Bream JH, et al. Interleukm 1 polymorphtsm associated with increased risk of gastric cancer. Nature 2000 ; 404 : 398-402 18 Correa P, van Doom LJ, Bravo JC, RUIZ B, Bravo LE, Realpe JL. Unsuccessful treatment results in survival of less virulent genotypes of Helrcobacter pylori in Colombian patients. Am J Gastroenterol 2000 ; 95 : 564-6. 19 Chiba N, Thomson AB, Sinclair P. From bench to bedside to bug: an update of climcally relevant advances in the care of persons with Helicobucfer pylori-associated dtsesaes Can J Gastroenterol2000 ; 14 : 188-98. 20 Peterson WL, Fendrick AM, Cave DR. Peura DA, Cgarabedtan-Ruffalo SM, Lame L. Hekobucter pylon-related disease: guidelmes for testtng and treatment, Arch Intern Med 2000 ; 160. 1285-91. 21 Jonsson B. Cost-effectiveness of Helicobucterp$on eradication therapy m duodenal ulcer disease. Stand J Gastroenterol 1996 ; 31 : 90-5. 22 Aokt T, Takayama S, Nimura H, Tsutsumt J. Effects of medical treatment on gastric mucosal abnormahties in gastroduodenal ulcer disease. World J Surg 2000 ; 24 : 321-7. 23 Graztella P. Chnn C, Capella C. Most gastric low-grade B-cell lymphomas of mucosa-associated lymphoid ttssue persist after Hekobacter pylori eradtcation. Ann Intern Med 2000 ; I32 : 846.
Association
of Helicobacter
24 Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni ‘M, et al. Regression of primary low-grade B-cell gastric lvmuhoma of mucosa-associated lvmohoid tissue tvne after eradication of Helicobacter pylori: Lancet 1993 ; 342 : 575-7. 25 Bayerdorfer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, et al. Regression or primary gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacterpylori. MALT Lymphoma Study group. Lancet 1995 ; 345 : 1591-4. 26 Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, et al. Cure of Helicobacter pylon’ infection and duration of remission of low-grade gastric mucosa-associated
pylori
361
and gastric cancer
lymphoid
i356-5.
tissue lymphoma. . _
J Nat1 Cancer
Inst 1997 ; 89 :
27 Ohashi S, Segawa K, Okamura S, Urano H, Kanamori S, Ishikawa H, et-al. A clinicopathologic study of gastric mucosaassociated lymphoid tissue lymphoma. Cancer 2000 ; 88 : 2210-9. 28 Alexander GA, Brawlew OW. Association of Helicobacter pylori infection with gastric cancer. Mil Med 2000 ; 165 : 21-7. 29 El-Omar EM. Oien K, Murrav LS, El-Nutumi A, Wirz A, Gillen D, et al. Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylon’. Gastroenterology 2000 ; 118 : 22-30.
SAS. All rights reserved
Editorial
Nonspecific but prognostic Helicobacter and gastric cancer association
pylori
G. Math6 Institut
Helicobacterpylori
/ gastritis
de Canc&ologie
/ gastric
et d’hmunologie & Hapita 92133 Issy-les-Mouheaux
dysplasia
I gastric
Suisse de Paris, BP 60, 6-10, cedex, France
rue Minard,
cancer
Helicobacterpylori (HP) has been discovered as a factor associated not only to gastric cancer (GC) at its neoplastic phase, but to all tumoral or pretumor phases, metastatis, dysplastic and even gastritic [ 11.This added bacteria to viruses and parasites in cancer epidemiology. It was not, however, simplifying the concept of the microorganism role in cancer pathogenesis: contrary to the usually specific and direct action of viruses, its role appeared to belong to nonspecific factors such as inflammation. In fact, the correlation between this bacteria’s presence and pre-cancer dysplasia is more frequent than that with established tumors. When the correlation of global HP and GC incidence is indeed replaced by those of GC stratified according to tumor stages and patients’ ages, it appears that the frequency of this bacterial presence is not only more often correlated with precancerous conditions than with established tumors, but that it is found more in young than in aged patients [ 1, 21. Haruma et al. [1], who published such results, considered that the role of HP was only situated at the level of gastritis, and that its presence essentially predicted the cancer risk of a gastritis. More interesting, HP incidences in the different gastric and pathologic conditions are not 100% [3]. All authors today have not only recognized that HP is found in several other types of gastric pathology than cancer, but even in peptic ulcer [4], gastroduodenal[5], enterogastric reflux [3,5], and even in intestinal gastric metaplasia [6,7]. Still more interesting and important is its lack of specificity as far as the type of cancer is concerned. It can be associated with adenocarcinoma, which suggests
its effect on gastric epithelium; it may also be associated with mucosa-associated lymphoid tissue (MALT) tumors, which are lymphomas [S, 91. Interestingly in this last case, it had first been considered that HP was most often associated with lowgrade B cell lymphoma. It was possibly associated to the t (11, 18) (q21, q 21) translocation type which results in c-IAP2-MALT l/MLT gene alteration [9]. Nakamura [9] distinguishes this ‘polypoid’ type of MALT-C lesion, from the forms he calls CR (MALTA), PR (MALT B) and NC (MALT-C), identified on the basis of their reactions to eradication of HP. But in fact, it can also be associated with high-grade MALT lymphoma [lo]. Some genes appear also to be important factors: thus the tag E and vat A S 1 genotypes are more prevalent in patients with gastric cancer than other genotypes. They are also prevalent in peptic ulcer [l I]. Statistics are complicated by the fact that it is sometimes impossible to distinguish lymphoid hyperplasias from lymphomas: clonal B-cell populations may be present in both reactive and neoplastic MALT tissues [ll, 121. In fact, HP is associated with several types of lesions, not only from lymphocytes (CD20, CD45, CD45RO) [I I], but from epithelial cells; metaplastic, as well as dysplastic and neoplastic epithelial clones have been observed [ 121. Not only can it affect lymphoid and epithelial cells, it can affect both simultaneously, inducing lymphoepithelial lesions [ 1 I]. It does not affect only the mucosal and lymphoid tissues; it can also affect the stroma, and be associated with fibroid polyps [ 131.
360
G. Math6
HP does not represent a specific risk of GC. It is accused of representing not only gastroduodenal lesions, but other organ attacks such as on the salivary glands [ 141. The question of HP genetics is also important. Patients with antibodies against lower-molecularweight proteins of HP, such as those of 19.5 and 26.5 kDa, could be at greatest risk [ 151. On the other hand, the effect of HP on adhesion molecules is important as well: coculture with HP induces an increase in luciferase activity in cells which transfers with a luciferase gene linked to the 5’-flanking region of the ICAM- 1 gene [ 161. Thus HP directly induces expression of ICAMon gastric epithelial cells, in an NF-kappa-dependant manner that may support leukocyte attachment during inflammation. Cytokines such as the interleukin- 1 gene cluster polymorphism suspected of enhancing production of IL1 -b are associated with hypochloremia induced by HP and with gastric cancer [ 171. The treatment would be less efficient in case of less virulent genotypes of HP [ 181. One of the most informative facts about the role of HP which still may be at this point associated, by chance or by interaction, is the effect of bacterial treatment. The most efficient combines ranitidine, bismuth citrate, and two antibodies: (such as clarithromycin and amoxicillin) for 10 to 14 days: the eradication rate is on the order of 80% [ 19,201. Omeprazole may replace ranitidine [21]. HZblockers have to be applied long-term
Ea. Does HP eradication induce regression, remission and/or cure? That is the question indeed. The answer is yes in case of low grade MALT + [23-271. Still more interesting is prevention [28]. Unfortunately the literature is confused. It seems that HP is more active on precancerous than on cancerous lesions
WI. REFERENCES Haruma K, Komoto K, Kamada T, Ito M, Kttadai Y, Yoshihara M, et al. Helicobucterpylori infection is a major risk factor for gastric carcinoma in young pattents. Stand J Gastroenterol 2000 ; 35 : 255-9. Kath R, Fiehler J, Schneider CP, Hoffken K. Gastric cancer in very young adults: apropos four patients and a review of the literature. J Cancer Res Clm Oncol2000 ; 126 : 233-7. Fallone CA, Barkun AN, Gottke MU, Best LM, Loo VG, Veldhuyzen van Zanten S, et al. Assoctatton of Helicobucter pylon genotype with gastroesophageal reflux disease and other’upper gastrointestinal diseases. Am J Gastroenteroi 2000 ,95 659-69. Hansson LE. Risk of stomach cancer in patients with peptic ulcer disease. World J Surg 2000 ; 24 : 3 15.20.
5 Von Holstein CS. Long-term prognosis after partial gastrectomy for gastroduodenal ulcer. World J Surg 2000 ; 24 : 307-14. 6 Xia HH, Kalantar JS, Talley NJ, Wyatt JM, Adams S, Chueng K, et al. Antral-type mucosa m the gastric incisura, body, and fundus (antralization): a lurk between Helicobacter pylori infection and intestinal metaplasia? Am J of Gastroenterol2000 : 95 : 114-21. pylon gastritis in 7 Smith VC, Genta RM. Role of Helicobacter gastrtc atrophy, intestinal metaplasia, and gastric neoplasia. Microsc Res Tech 2000 ,48 : 313-20. B-cell 8 Pinottt G, Chmi C, Capella C. Most gastric low-grade lymphomas of mucosa-assoctated lymphoid tissue persist after Helicobacter pylori eradication Ann Intern Med 2000 , 132 : 846. T, Nakamura S, Yonezumt M, Suzuki T, Mat9 Nakamura suura A, Yatabe Y, et al. Helicobacter pvlori and the t (1 I, 18) (q21; q21) translocatton m gastric low-grade B-cell lymphoma of mucosa-associated lymphotd tissue type. Jpn J Cancer Res 2000 ; 91 : 301-9 10 Boot H, de Jong D, van Heerde P, Taal B. Role of Helicobacter eradtcatton m high grade MALT iymphoma. Lancet 1995 ; 346 : 448-9. 11 Saxena A, Moshynska 0, Kanthan R, Bhutan1 M, Maksymurk AW, Lukie BE. Distinct B-cell clonal bands m Helicobucterpylori gastritis wtth lymphoid hyperplasia. J Pathology 2000 ; 190 : 47-54. 12 Testino G, Comaggia M, Testino R, Valentini M. The phystopathological aspects of chronic gastritis, Helicobacferpylori and precancerous gastrtc changes. Recenti Prog Med 2000 ; 91 : 186-90. 13 Shalom A, Wasserman I. Segal M. Orda R Inflammatory fibroid polyp and Helicobacter pylori. Aetiology or coincidence? Em J Surg 2000 , 166 54-7. 14 Dev DE. Eradication de H. p?lori contre MALT salivatre. Lancet 1996 ; XX : 268-9. 15 Shtesh SC, Sheu B.S. Yang HB. Tsao HJ, Lin XZ. Serologic response to lower-molecular-wetght proteins of H. pylon 1s related to cluucal outcome of H. p~lori mfectton in Taiwan. Dig Dts Sci 2000 ; 45 781-8. 16 Infect Immun 2000 : 68 : 1806- 14. EM, Carrtngton M. Chow WH, MC Coil KE, 17 El-Omar Bream JH, et al. Interleukm 1 polymorphtsm associated with increased risk of gastric cancer. Nature 2000 ; 404 : 398-402 18 Correa P, van Doom LJ, Bravo JC, RUIZ B, Bravo LE, Realpe JL. Unsuccessful treatment results in survival of less virulent genotypes of Helrcobacter pylori in Colombian patients. Am J Gastroenterol 2000 ; 95 : 564-6. 19 Chiba N, Thomson AB, Sinclair P. From bench to bedside to bug: an update of climcally relevant advances in the care of persons with Helicobucfer pylori-associated dtsesaes Can J Gastroenterol2000 ; 14 : 188-98. 20 Peterson WL, Fendrick AM, Cave DR. Peura DA, Cgarabedtan-Ruffalo SM, Lame L. Hekobucter pylon-related disease: guidelmes for testtng and treatment, Arch Intern Med 2000 ; 160. 1285-91. 21 Jonsson B. Cost-effectiveness of Helicobucterp$on eradication therapy m duodenal ulcer disease. Stand J Gastroenterol 1996 ; 31 : 90-5. 22 Aokt T, Takayama S, Nimura H, Tsutsumt J. Effects of medical treatment on gastric mucosal abnormahties in gastroduodenal ulcer disease. World J Surg 2000 ; 24 : 321-7. 23 Graztella P. Chnn C, Capella C. Most gastric low-grade B-cell lymphomas of mucosa-associated lymphoid ttssue persist after Hekobacter pylori eradtcation. Ann Intern Med 2000 ; I32 : 846.
Association
of Helicobacter
24 Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni ‘M, et al. Regression of primary low-grade B-cell gastric lvmuhoma of mucosa-associated lvmohoid tissue tvne after eradication of Helicobacter pylori: Lancet 1993 ; 342 : 575-7. 25 Bayerdorfer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, et al. Regression or primary gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacterpylori. MALT Lymphoma Study group. Lancet 1995 ; 345 : 1591-4. 26 Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, et al. Cure of Helicobacter pylon’ infection and duration of remission of low-grade gastric mucosa-associated
pylori
361
and gastric cancer
lymphoid
i356-5.
tissue lymphoma. . _
J Nat1 Cancer
Inst 1997 ; 89 :
27 Ohashi S, Segawa K, Okamura S, Urano H, Kanamori S, Ishikawa H, et-al. A clinicopathologic study of gastric mucosaassociated lymphoid tissue lymphoma. Cancer 2000 ; 88 : 2210-9. 28 Alexander GA, Brawlew OW. Association of Helicobacter pylori infection with gastric cancer. Mil Med 2000 ; 165 : 21-7. 29 El-Omar EM. Oien K, Murrav LS, El-Nutumi A, Wirz A, Gillen D, et al. Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylon’. Gastroenterology 2000 ; 118 : 22-30.