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Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

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 %), χ(2) = 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.

SUBMITTER: Hnatyszyn A

PROVIDER: S-EPMC3898137 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe present study aims to investigate the effect of Helicobacter pylori (Hp) infection on gastric mucosal microbiota in patients with chronic gastritis.MethodsHere recruited a population of 193 patients with both chronic gastritis and positive rapid urease, including 124 patients with chronic atrophic gastritis (CAG) and 69 patients with chronic non-atrophic gastritis (nCAG). Immunoblotting was used to detect four serum Hp antibodies (UreA, UreB, VacA and CagA) to determine the types of virulent Hp-I and avirulent Hp-II infections. Gastric microbiota was profiled by 16S rRNA gene V3-V4 region, and R software was used to present the relationship between the microbial characteristics and the type of Hp infection.ResultsIn the stomach of patients with Hp-positive gastritis, the dominant gastric bacterial genera included Ralstonia (23.94%), Helicobacter (20.28%), Pseudonocardia (9.99%), Mesorhizobium (9.21%), Bradyrhizobium (5.05%), and Labrys (4.75%). The proportion of Hp-I infection was significantly higher in CAG patients (91.1%) than in nCAG patients (71.0%) (P < 0.001). The gastric microbiota richness index (observed OTUs, Chao) was significantly lower in CAG patients than in nCAG patients (P <0.05). Compared with avirulent Hp-II infection, virulent Hp-I infection significantly decreased the Shannon index in CAG patients (P <0.05). In nCAG patients, Hp-I infected patients had lower abundances of several dominant gastric bacteria (Aliidiomarina, Reyranella, Halomonas, Pseudomonas, Acidovorax) than Hp-II infected patients. Meanwhile, in CAG patients, Hp-I infected patients occupied lower abundances of several dominant oral bacteria (Neisseria, Staphylococcus and Haemophilus) than Hp-II infected patients. In addition, bile reflux significantly promoted the colonization of dominant oral microbiota (Veillonella, Prevotella 7 and Rothia) in the stomach of CAG patients. There was no significant symbiotic relationship between Helicobacter bacteria and non-Helicobacter bacteria in the stomach of nCAG patients, while Helicobacter bacteria distinctly linked with the non-Helicobacter bacteria (Pseudolabrys, Ralstonia, Bradyrhizobium, Mesorhizobium and Variovorax) in CAG patients.ConclusionsVirulent Hp infection alters the gastric microbiota, reduces microbial diversity, and enhances the symbiotic relationship between the Helicobacter bacteria and non-Helicobacter bacteria in patients with chronic gastritis. The data provides new evidence for treating Hp infection by improving the gastric microbiota.

Project description:Background and aimsMicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population.MethodsGene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR.ResultsOverall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC.ConclusionsGene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects.

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Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

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