ABSTRACT
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.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Gastritis/genetics , Helicobacter pylori , Helicobacter Infections/genetics , Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-1beta/genetics , Stomach Neoplasms/genetics , Tumor Necrosis Factor-alpha/genetics , Alleles , Brazil , Chronic Disease , DNA, Bacterial/analysis , Genetic Predisposition to Disease , Genotype , Gastritis/immunology , Gastritis/microbiology , Helicobacter Infections/immunology , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Stomach Neoplasms/immunology , Stomach Neoplasms/microbiologyABSTRACT
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-1ß, 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-1ß, 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-1ß -511 C/C and IL-1ß -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-1ß -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-1ß -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.
Subject(s)
Gastritis/genetics , Helicobacter Infections/genetics , Helicobacter pylori , Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-1beta/genetics , Stomach Neoplasms/genetics , Tumor Necrosis Factor-alpha/genetics , Adult , Aged , Aged, 80 and over , Alleles , Brazil , Chronic Disease , DNA, Bacterial/analysis , Female , Gastritis/immunology , Gastritis/microbiology , Genetic Predisposition to Disease , Genotype , Helicobacter Infections/immunology , Humans , Male , Middle Aged , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Stomach Neoplasms/immunology , Stomach Neoplasms/microbiology , Young AdultABSTRACT
The aim of the present study was to evaluate the influence of Helicobacter pylori on MLH1 and MGMT mRNA levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression levels of MLH1 and MGMT were determined by quantitative real-time PCR and immunohistochemistry. There was an association between infection with cagA, vacA s1m1 strains and gastric cancer development. When the gastric epithelium and associated inflammation were examined for expression of MLH1 and MGMT, an overall increase in expression was observed. On the other hand, these levels decrease significantly among gastric cancer patients. The loss of MLH1 and MGMT expression in gastric cancer patients suggests that it is not an early event in H. pylori-associated gastric carcinogenesis.
Subject(s)
Adaptor Proteins, Signal Transducing/biosynthesis , DNA Modification Methylases/biosynthesis , DNA Repair Enzymes/biosynthesis , Gastritis/pathology , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Nuclear Proteins/biosynthesis , Stomach Neoplasms/pathology , Tumor Suppressor Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/microbiology , Gene Expression Profiling , Helicobacter Infections/microbiology , Humans , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Male , Middle Aged , MutL Protein Homolog 1 , Stomach Neoplasms/microbiology , Young AdultABSTRACT
Aflatoxin B1 (AFB1) is among the most potent naturally occurring carcinogens and classified as a group I carcinogen. Since the ingestion of aflatoxin-contaminated food is associated with several liver diseases, the aim of the present study was to evaluate the effect of 2, 20, and 200 ppb of AFB1 on DNA damage in peripheral blood lymphocytes and liver cells in Dunkin-Hartley guinea pigs. The animals were divided into four groups according to the given diet. After the treatment the lymphocytes and liver cells were isolated and DNA damage determined by Comet assay. The levels of DNA damage in lymphocytes were higher animals treated with 200 ppb of AFB1-enriched diet (P = 0.02). In the liver cells there were a relationship between the levels of DNA damage and the consumption of AFB1 in all studied groups. These results suggest that Comet assay performed on lymphocytes is a valuable genotoxic marker for high levels of exposure to AFB1 in guinea pig. Additionally our results indicate that the exposure to this toxin increases significantly and increases the level of DNA damage in liver cells, which is a key step on liver cancer development. We also suggest that the Comet assay is an useful tool for monitoring the genotoxicity of AFB1 in liver.
