Abstract
Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of –889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism –889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ2 = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04–2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.
Highlights
The development of inflammatory conditions of the gastric mucosa is a complex and multi factorial process associated with balance disturbances between aggression and defence compounds
The present study examined the role of IL1A and IL1B polymorphisms and the co-existence of H. pylori infection proinflammatory IL-10 genotypes, tumour necrosis factor (TNF)-a, IL1B and the IL-1 receptor antagonist increases the risk of development of gastric carcinoma
In the case of the Japanese population, IL1B– 511C[C polymorphism was found dominant among patients with advanced atrophic chronic gastritis, whereas IL1B–511T[T?T[C polymorphism dominated among the Chinese population
Summary
The development of inflammatory conditions of the gastric mucosa is a complex and multi factorial process associated with balance disturbances between aggression and defence compounds. The development of chronic gastritis is strongly associated with the infection of Helicobacter pylori whose link with the spread of cancer has been confirmed beyond any doubt A significant achievement leading to the recognition of mechanisms causing the disease was the isolation and culturing, in 1983 by Warren and Marshall, from the gastric mucosa of Campylobacter pylori bacteria. In their studies, they documented a link between the infection and gastritis (Warren and Marshall 1983). The development of the chronic inflammation of the gastric mucosa and, gastric carcinoma can be affected by an individual, genetically preconditioned response to the infection. One of the consequences of H. pylori presence, like in case of other infectious agents, especially viruses, is change of methylation profile of infected tissue, which can lead to precancerous state (De Falco et al 2011; Maekita et al 2006)
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