Carbonate Ions and Gastric Cancer

Roy Ehrnström

Research output: ThesisDoctoral Thesis (compilation)

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Abstract

Nearly one million new cases of gastric cancer are diagnosed annually throughout the world. Even though the incidence has fallen dramatically in recent decades, this disease is still the second leading cause of cancer death in a global perspective. The geographic distribution of gastric cancer varies markedly, with the highest rates in Asian countries such as Japan, Korea, and China. This variation is presumably associated with modifiable risk factors, primarily H. pylori infection and diet, which have dominated the debate on this topic for more than a decade. The incidence of spontaneous gastric cancer is extremely low in rats, which has led to testing of different experimental models in attempts to generate gastric tumors in these animals. In the first study underlying this thesis, rats were subjected to gastric resection to generate duodenogastric reflux (DGR) and subsequent development of gastric adenocarcinomas. The effects of various food supplements on the incidence of cancer were studied using a total of 256 male Wistar rats. Surprisingly, in the first set of experiments in the second study, ingestion of food supplemented with calcium carbonate more than tripled the incidence of carcinomas (61%) compared to controls (17%). In a second set of experiments, calcium ions were switched to sodium ions, which revealed that carbonate ions caused the remarkable increase in cancer in the rats given an altered diet (54%, compared to 12% for controls). Both experimental and clinical studies have shown that DGR is associated with the development of gastric cancer. It has also been found that pancreaticoduodenal juice is responsible for the neoplastic formation, and that such fluid is especially rich in carbonate ions. The final study examined non-transformed mucosa in a rat model of gastric cancer to determine expression of COX-2 and ODC as markers of tumor promotion and to measure production of Ki67 as an indication of cell proliferation. This was done to assess the effect of carbonate ions on gastric tumorigenesis. The results indicated that the gastric resection per se increased COX-2 expression and significantly augmented cell proliferation. Dietary supplementation of carbonate ions did not further enhance the levels of COX-2. However, in the resected animals, carbonate-supplemented food led to elevated expression of ODC and a further increase in cell proliferation in the non-transformed mucosa. In conclusion, an environment entailing persistent chronic inflammation and increased levels of COX-2, induced by either duodenogastric reflux or a factor such as H. pylori infection, increases the risk of malignant transformation. Moreover, extra carbonate intake raises the levels of ODC in the gastric mucosa in a COX-2-dependent manner, which magnifies the proliferative drive and results in an even higher risk of gastric carcinoma.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Pathology, Malmö
Supervisors/Advisors
  • Andersson, Tommy, Supervisor
Award date2007 Feb 9
Publisher
Print ISBNs91-85559-86-5
Publication statusPublished - 2007

Bibliographical note

Defence details

Date: 2007-02-09
Time: 09:00
Place: Patologiska Institutionens föreläsnings-sal, Ingång 78, Universitetssjukhuset UMAS i Malmö

External reviewer(s)

Name: Lundell, Lars
Title: Professor
Affiliation: Enheten för Kirurgi, Karolinska Universitetssjukhetet, Stockholm

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<div class="article_info">Roy Ehrnström, Clas G Lindström, Stefan Arvidsson, Nils H Sternby, Elise Nilsson and Ylva Ehrnström. <span class="article_issue_date">1995</span>. <span class="article_title">An experimental study of gastric stump carcinoma in Wistar rats</span> <span class="journal_series_title">APMIS</span>, <span class="journal_volume">vol 103</span> <span class="journal_pages">pp 878-884</span>. <span class="journal_distributor">Department of Pathology, University of Lund, Malmo University Hospital, Sweden.</span></div>
<div class="article_info">Roy Ehrnström, Béla Veress, Stefan Arvidsson, Nils H Sternby, Tommy Andersson and Clas G Lindström. <span class="article_issue_date">2006</span>. <span class="article_title">Dietary supplementation of carbonate promotes spontaneous tumorigenesis in a rat gastric stump model</span> <span class="journal_series_title">Scandinavian Journal of Gastroenterology</span>, <span class="journal_volume">vol 41</span> <span class="journal_pages">pp 12-20</span>. <span class="journal_distributor">Divisions of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.</span></div>
<div class="article_info">Roy Ehrnström, Otto Ljungberg, Monica Haglund, Lars Magnus Bjursten, Clas G Lindström and Tommy Andersson. <span class="article_issue_date">2007</span>. <span class="article_title">Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer</span> <span class="journal_series_title">International Journal of Cancer</span>, <span class="journal_distributor">Divisions of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.</span> (submitted)</div>

Subject classification (UKÄ)

  • Cancer and Oncology
  • Cell and Molecular Biology

Keywords

  • Medicine (human and vertebrates)
  • ODC
  • COX-2
  • inflammation
  • Wistar rats
  • duodenogastric reflux
  • Medicin (människa och djur)
  • proliferation
  • gastrojejunostomy
  • carbonate ions
  • Experimental gastric cancer

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