RESUMO
It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Gastrite/genética , Helicobacter pylori , Infecções por Helicobacter/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Neoplasias Gástricas/genética , Fator de Necrose Tumoral alfa/genética , Alelos , Brasil , Doença Crônica , DNA Bacteriano/análise , Predisposição Genética para Doença , Genótipo , Gastrite/imunologia , Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologiaRESUMO
Background: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. Aim: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. Material and Methods: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. Results: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95 percent confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95 percentCI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95 percentCI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95 percentCI 0.01-0.65). Conclusions: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/genética , Helicobacter pylori/imunologia , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Polimorfismo Genético/genética , Neoplasias Gástricas , Estudos de Casos e Controles , Colômbia/etnologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/genética , Imunoglobulina G/sangue , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologiaRESUMO
Background: The damaging capacity of Helicobacter pylori is variable and depends, in part, on its genetic polymorphism. Aim: To study H pylori genes vacA, cagA and iceA and the relationship of these genotypes with the features of acute damage in chronic gastritis. Material and methods: Gastric endoscopic biopsies were obtained in 75 adults for pathological study and genetic typification of H pylori by specific PCR. Results: In only 64 cases, complete information was available. In 53 of these, there was H pylori infection demonstrated by PCR. Twenty one percent had infection by two or more H pylori strains, vacA gene had genotypes s2/m2, s1/m1 and s1/m2 in 36, 25 and 8% of cases respectively, cagA gene was present in 49% of infected patients. iceA gene had genotypes iceA 1 ad iceA 2 in 15 and 60% of patients respectively. The presence of cagA or alleles s1/m1 and s1/m2 of vacA gene was directly correlated with polymorphonuclear infiltration and the severity of epithelial damage. The genotype s2/m2 of vacA gene was significantly associated with a milder or absent mucosal damage. No association was found between iceA alleles and the pathological features of gastritis. Conclusions: Alleles of vacA and cagA genes of H pilory are associated with the severity of gastric mucosal damage.