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http://dx.doi.org/10.7314/APJCP.2015.16.4.1315

Proton Pump Inhibitors and Helicobacter Pylori-Associated Pathogenesis  

Hagiwara, Tadashi (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science)
Mukaisho, Ken-Ichi (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science)
Nakayama, Takahisa (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science)
Hattori, Takanori (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science)
Sugihara, Hiroyuki (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.4, 2015 , pp. 1315-1319 More about this Journal
Abstract
The fact that long-term use of proton pump inhibitors (PPIs) aggravates corpus atrophic gastritis in patients with Helicobacter pylori infection has been proven clinically and experimentally. Corpus atrophic gastritis is a known risk factor for gastric cancer. Therefore, gastric neoplasia might be associated with the long-term use of PPIs. One of the causes of worsening corpus atrophic gastritis, leading to the development of adenocarcinoma, might be bacterial overgrowth under conditions of hypochlorhydria. The production of potentially carcinogenic N-nitrosocompounds by nitrosating organisms under conditions of hypochlorhydria might be associated with carcinogenesis. Interactions between bile acids, pH, and H. pylori might also contribute to carcinogenicity, especially in patients with gastro-esophageal reflux disease (GERD). The concentration of soluble bile acids, which have bactericidal or chemorepellent properties toward H. pylori, in gastric contents is considerably higher in patients undergoing continuous PPI therapy than in healthy individuals with normal acid production. Under these circumstances, H. pylori might colonize the stomach body rather than the pyloric antrum. Hypergastrinemia induced by PPI administration might promote the development of gastric cancer. Because the main cause of corpus atrophic gastritis is H. pylori infection, and not PPI administration, H. pylori infection should be eradicated before starting long-term PPI therapy.
Keywords
Helicobacter pylori; proton pump inhibitors; gastric cancer; corpus atrophic gastritis; GERD; gatrin;
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1 Andersson AF, Lindberg M, Jakobsson H, et al (2008). Comparative analysis of human gut microbiota by barcoded pyrosequencing. PLoS One, 3, 2836.   DOI   ScienceOn
2 Bik EM, Eckburg PB, Gill SR, et al (2006). Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci USA, 103, 732-7.   DOI
3 Correa P, Haenszel W, Cuello C, et al (1975). Archer M. A model for gastric cancer epidemiology. Lancet, 2, 58-9.
4 Correa P (1984). Chronic gastritis as a cancer precursor. Scand J Gastroenterol Suppl, 104, 131-6.
5 Correa P (1992). Human gastric carcinogenesis: a multistep and multifactorial process-- First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res, 52, 6735-40.
6 Cover TL, Blaser MJ (2009). Helicobacter pylori in health and disease. Gastroenterology, 136, 1863-73.   DOI
7 Dixon MF, Neville PM, Mapstone NP, et al (2001). Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux? Gut, 49, 359-63.   DOI
8 Franco AT, Israel DA, Washington MK, et al (2005). Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc. Natl Acad Sci USA, 102, 10646-51.   DOI   ScienceOn
9 Fox JG, Rogers AB, Ihrig M, et al (2003). Helicobacter pyloriassociated gastric cancer in INS-GAS mice is gender specific. Cancer Res, 63, 942-50.
10 Fox JG, Kuipers EJ (2011). Long-term proton pump inhibitor administration, H pylori and gastric cancer: lessons from the gerbil. Gut, 60, 567-8.   DOI
11 Garcia Rodriguez LA, Lagergren J, Lindblad M, et al (2006). Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK. Gut, 55, 1538-44.   DOI
12 Geboes K, Dekker W, Mulder CJ, et al (2001). Long-term lansoprazole treatment for gastro-oesophageal reflux disease: clinical efficacy and influence on gastric mucosa. Aliment Pharmacol Ther, 15, 1819-26.   DOI
13 Graham DY, Opekun AR, Osato MS, et al (2004). Challenge model for Helicobacter pylori infection in human volunteers. Gut, 53, 1235-43.   DOI
14 Hagiwara T, Mukaisho M, Ling ZQ, et al (2007). Rebamipide contributes to reducing adverse effects of long-term administration of omeprazole in rats. Dig Dis Sci, 52, 988-94.   DOI
15 Hagiwara T, Mukaisho M, Nakayama T, et al (2011). Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori. Gut, 60, 624-30.   DOI
16 Hagiwara T, Mukaisho M, Nakayama T, et al (2012). Experimental strategies for induction of gastric adenocarcinomas under long-term proton pump inhibitor administration and Helicobacter pylori infection. Asian Pac J Cancer Prev, 13, 3005-6   DOI
17 Havu N (1986). Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. Digestion, 35, 42-55.   DOI
18 Havu N, Mattsson H, Ekman L, et al (1990). Enterochromaffinlike cell carcinoids in the rat gastric mucosa following longterm administration of ranitidine. Digestion, 45, 189-95.   DOI
19 Hawkey CJ, Karrasch JA, Szczepanski L, et al (1998). Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group. N Engl J Med, 338, 727-34.   DOI
20 Hill M (1985). Normal and pathological microbial flora of the upper gastrointestinal tract. Scand J Gastroenterol Suppl, 111, 1-6.
21 Honda S, Fujioka T, Tokieda M, et al (1998a). Gastric ulcer, atrophic gastritis, and intestinal metaplasia caused by Helicobacter pylori infection in Mongolian gerbils. Scand J Gastroenterol, 33, 454-60.
22 Honda S, Fujioka T, Tokieda M, et al (1998b). Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res, 58, 4255-9.
23 IARC Monographs on the Evaluation of Carcinogen risk to humans: some industrial chemicals, (1994) No. 60, Lyon: International Agency for Research on Cancer.
24 Kuipers EJ, Pena AS, Kamp GV, et al (1993). Seroconversion for Helicobacter pylori. Lancet, 342, 328-31.   DOI
25 Kuipers EJ, Uyterlinde AM, Pena AS, et al (1995). Increase of Helicobacter pylori-associated corpus gastritis during acid suppressive therapy: implications for longterm safety. Am J Gastroenterol, 90, 1401-6.
26 Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al (1996). Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med, 334, 1018-22.   DOI
27 Lee A, Fox AJ, Otto G, et al (1990). A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology, 99, 1315-23.   DOI
28 Lee A, O'Rourke J, De Ungria MC, et al (1997). A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology, 112, 1386-97.   DOI
29 Lofgren JL, Whary MT, Ge Z, et al (2011). Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology, 140, 210-20.   DOI
30 Li XX, Wong GL, To KF, et al (2009). Bacterial microbiota profiling in gastritis without Helicobacter pylori infection or non-steroidal anti-inflammatory drug use. PLoS One, 4, 7985.   DOI
31 Marshall BJ, Warren JR (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet, 1, 1311-15.
32 Martinsen TC, Bergh K, Waldum HL (2005). Gastric juice: a barrier against infectious diseases. Basic Clin Pharmacol Toxicol, 96. 94-102.   DOI
33 Matsumoto S, Washizuka Y, Matsumoto Y, et al (1997). Induction of ulceration and severe gastritis in Mongolian gerbil by Helicobacter pylori infection. J Med Microbiol, 46, 391-7.   DOI
34 Mattsson H, Havu N, Brautigam J, et al (1991). Partial gastric corpectomy results in hypergastrinemia and development of gastric enterochromaffinlike-cell carcinoids in the rat. Gastroenterol, 100, 311-9.   DOI
35 Meikle DD, Taylor KB, Truelove SC, et al (1976). Gastritis duodenitis, and circulating levels of gastrin in duodenal ulcer patients before and after vagotomy. Gut, 17, 719-28.   DOI
36 Mukaisho K, Hagiwara T, Nakayama T, et al (2014). Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD. World J Gastroenterol, 20, 11962-5.   DOI
37 Nair PP, Kritchenvski D (1971). The Bile Acids: Chemistry, Physiology and Metabolism. Chemistry. New York: Plenum Press, 1.
38 Shafaghi A, Mansour-Ghanaei F, Joukar F, et al (2013). Serum gastrin and the pepsinogen I/II ratio as markers for diagnosis of premalignant gastric lesions. Asian Pac J Cancer Prev, 14, 3931-6.   DOI   ScienceOn
39 Orlando LA, Lenard L, Orlando RC, et al (2007). Chronic hypergastrinemia: causes and consequences. Dig Dis Sci, 52, 2482-9.   DOI
40 Polk DB, Peek Jr RM (2010). Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer, 10, 403-14.   DOI   ScienceOn
41 Stamp DH (2002). Three hypotheses linking bile to carcinogenesis in the gastrointestinal tract: certain bile salts have properties that may be used to complement chemotherapy. Med Hypotheses, 59, 398-405.   DOI
42 Sheh A, Fox JG (2013). The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis. Gut Microbes, 4, 505-31.   DOI
43 Sordal O, Waldum H, Nordrum IS, et al (2013). The gastrin receptor antagonist netazepide (YF476) prevents oxyntic mucosal inflammation induced by Helicobacter pylori infection in Mongolian gerbils. Helicobacter, 18, 397-405.   DOI
44 Targownik LE, Metge CJ, Leung S, et al (2008). The relative efficacies of gastroprotective strategies in chronic users of nonsteroidal anti-inflammatory drugs. Gastroenterology. 134, 937-44.   DOI
45 Tsukamoto H, Mizoshita T, Sasaki M, et al (2011). Longterm high-dose proton pump inhibitor administration to Helicobacter pylori-infected Mongolian gerbils enhances neuroendocrine tumor development in the glandular stomach. Asian Pac J Cancer Prev, 12, 1049-54.
46 Uemura N, Okamoto S, Yamamoto S, et al (2001). Helicobacter pylori infection and the development of gastric cancer. Engl J Med. 345, 784-9.   DOI
47 Watanabe T, Tada M, Nagai H, et al (1998). S. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterol, 115, 642-8.   DOI
48 N. Wang TC, Fox JG (1998). Helicobacter pylori and gastric cancer: Koch's postulates fulfilled? Gastroenterol, 115, 780-3.   DOI
49 Wang TC, Dangler CA, Chen D, et al (2000). Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology, 118, 36-47.   DOI
50 Warren JR, Marshall BJ (1983). Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet, 1, 1273-5.
51 Watson SA, Grabowska AM, El-Zaatari M, et al (2006). Gastrin-active participant or bystander in gastric carcinogenesis? Nature Rev Cancer, 6, 936-46.   DOI
52 Worku ML, Karim QN, Spencer J, et al (2004). Chemotactic response of Helicobacter pylori to human plasma and bile. J Med Microbiol, 53, 807-11.   DOI
53 Xu GP, Reed PI (1993). N-nitroso compounds in fresh gastric juice and their relation to intragastric pH and nitrite employing an improved analytical method. Carcinogenesis, 14, 2547-51.   DOI
54 Yokota K, Kurebayashi Y, Takayama Y, et al (1991). Colonization of Helicobacter pylori in the gastric mucosa of Mongolian gerbils. Microbiol Immunol, 35, 475-80.   DOI
55 Ziebarth D, Spiegelhalder B, Bartsch H (1997). N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori. Carcinogenesis, 18, 383-9.   DOI