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Gastric diseases such as chronic gastritis and gastric cancer are most commonly caused by virulence factors of Helicobacter pylori (H. pylori), such as the vacA, cagA, dupA and oipA genes. Therefore, this study investigated the prevalence and the combination of these virulence factors from patients with gastric diseases. The endoscopic biopsies were obtained from 516 patients with gastric symptoms, 101 of which were from patients with normal gastric tissue, 365 of which were from patients with chronic gastritis, and 50 of which were from patients with gastric cancer. H. pylori and the virulence factors were detected by PCR. The oipA gene exhibited an increased risk for chronic gastritis (p = 0.0296), and the vacA gene demonstrated a risk for gastric cancer from chronic gastritis (p = 0.0002). Based on the combination of the virulence factors, cagA, vacA, dupA and oipA genes exhibited a high prevalence in patients with chronic gastritis and gastric cancer. The cagA+/dupA+ genotype demonstrated a significant correlation in patients with normal gastric mucosa (p = 0.0278). In the chronic gastritis group, a significant association was observed between the cagA+ and the vacA s1m1 genotypes (p cagA+/dupA+ genotypes (p = 0.0183), the dupA+/oipA+ genotypes (p cagA, vacA, dupA, and oipA genes, which contributed to the risk of developing gastroduodenal diseases. Furthermore, this is the first study to reveal a high prevalence of the oipA gene in H. pylori isolates in Brazil.

Objective To investigate an association between the interleukin-1β (IL-1β)−511 T>C (rs16944), −31 C>T (rs1143627), and/or interleukin-1 receptor antagonist (IL-1RA) polymorphisms and gastritis and then to correlate any associations with the presence of Helicobacter pylori ( H. pylori ), cagA and vacA genes. Methods Gastric biopsies were obtained from 377 children with gastric symptoms including 152 males and 225 females aging from 1–15 years with the mean age of (9.41 ± 4.29) years. To characterize the −511 T>C, −31 C>T, and IL-1RA polymorphisms, the PCR-RFLP and PCR-VNTR methods were used. PCR was also used for the diagnosis of H. pylori and to determine whether cagA and vacA genes were present. Results The histopathological analysis revealed 206 patients (54.6%) with gastritis and 171 patients (45.4%) with normal gastric tissue. Subjects carrying the −511 T/T genotype were associated with a risk of gastritis (odds ratio (OR) = 2.75, 95% confidence interval ( CI ) 1.45–5.18, P = 0.0035). Similar results were found in subjects carrying −31 C/C (OR = 2.27, 95% CI 1.13–4.54, P = 0.0440). However, the IL-1RA polymorphism did not seem to be associated with gastric disease (OR = 1.38, 95% CI 0.58–3.26, P = 0.2400). Conclusions This data suggests that IL-1β gene cluster polymorphisms and, more specifically, interactions between these polymorphisms and H. pylori may be predictors of gastritis risks, which possibly play a relevant role in the susceptibility to or the development of gastric disease early in life.

Sao Paulo Research Foundation miRNAs appear to play an important role in controlling the expression of several genes, and they are a potential biomarker and prognostic tool in gastric diseases. We analyzed 53 controls, 86 patients with gastritis, and 19 patients with gastric cancer. Real-time-PCR was used to determine the expression levels of miRNA-146a, miRNA-155, IL-2, and TNF-. The subsequent analysis of the target genes was performed using the bioinformatics approach. There was no difference in IL-2 expression between the groups. However, there was a significant increase in TNF- expression in the gastritis group relative to the control and a significant decrease in the gastric cancer group relative to the control. There was also a statistically significant increase in miRNA-146a and miRNA-155 expression in the gastritis group relative to the control, but not in the gastric cancer group. Similar results were found when the presence of H. pylori was considered. The data revealed an increase in miRNA-146a and miRNA-155 expression but not enough to control the expression of TNF-. The presence of H. pylori was found to affect increases in TNF- and microRNA expression, and miRNA-146a and miRNA-155 alone were not able to eliminate bacteria or restore tissue homeostasis. Universidade do Sagrado Coração (USC), Bauru, Sao Paulo, Brazil Univ Fed Sao Paulo UNIFESP, Sao Paulo, SP, Brazil Univ Fed Sao Paulo UNIFESP, Sao Paulo, SP, Brazil FAPESP: 2015/11371-5 FAPESP: 2015/11613-9 Web of Science

This study investigated miRNA-181c expression in control patients (healthy gastric mucosa), patients with gastritis, and patients with gastric cancer. The presence of Helicobacter pylori was determined, and the associations between H. pylori infection, levels of miRNA-181c expression, and gastric disease were also analyzed. A total of 158 subjects were included in the study, and the three groups were respectively composed of 53 controls, 86 patients with gastritis, and 19 patients with gastric cancer. miRNA-181c expression and H. pylori infection were determined by quantitative real-time PCR and PCR, respectively. The subsequent target gene analysis was performed using the bioinformatics approach to understand the possible mechanisms of gastric cancer. We determined significantly lower miRNA-181c expression in the gastric cancer group when compared to the control and gastritis groups, regardless of the presence of H. pylori. There was no difference in miRNA-181c expression between the control group and gastritis group, whether the presence of H. pylori was considered or not. The bioinformatics approach identified several genes as possible targets for miRNA-181c, including the X-linked inhibitor of apoptosis (XIAP) gene (which encodes a protein that belongs to a family of apoptotic suppressor proteins), the caspase 9 gene, and the caspase 3 gene. All target genes identified may be involved in gastric cancer and apoptosis pathways. The results suggest that the presence of H. pylori has no influence on microRNA expression and that the downregulation of miR-181c may play an important role in gastric cancer progression by controlling important genes associated with apoptosis. Therefore, miRNA-181c may be a potential marker of gastric cancer.

Gastritis caused by infection with Helicobacter pylori is characterized by chronic inflammation and damage in gastric tissue, which is a main risk factor for gastric cancer. Associated with H. pylori, the TP53 gene tumor suppressor and the cell adhesion glycoprotein epithelial cadherin develop a relevant role in the integrity and carcinogenesis of the epithelium. We aimed to detection of H. pylori and its main virulence markers and measured the messenger RNA (mRNA) expression levels of E-cadherin and TP53 genes. The detection of H. pylori and its virulence markers, as well as the mRNA expression levels of E-cadherin and TP53 genes, were obtained for 161 samples of gastric biopsies including 37 with normal gastric tissue, 70 with gastritis, 24 from neoplastic tissue, and 27 from adjacent non-neoplastic by means of a quantitative real-time polymerase chain reaction. The mRNA expression levels of E-cadherin and TP53 were found to be decreased in patients with gastritis, independently of H. pylori infection. In samples from gastric patients, the neoplastic tissue showed an accentuated decrease of expression; on the other hand, the expression of E-cadherin was normal in adjacent non-neoplastic. No evidence was found of the involvement of the cagA and vacA genes in the decreased expression of E-cadherin and TP53. The process of carcinogenesis is complex, and the decrease of the E-cadherin gene expression and TP53 gene expression appears to contribute significantly.

Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms +114 T > G (rs2069763) and −330 T > G (rs2069762) and the development of gastric cancer; these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). PCR-RFLP was used to characterize the +114 T > G and −330 T > G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR = 6.43, 95% CI: 1.47–28.10, p = 0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR = 4.47, 95% CI: 1.84–10.84, p = 0.0022). When the IL-2 +114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR = 5.97, 95% CI: 1.60–22.27, p = 0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR = 6.36, 95% CI: 2.66–15.21, p < 0.0001). The haplotype was also analyzed. The −330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the −330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the −330G/+114T haplotype.

Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of theTNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer

Background Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pylori appear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor of Helicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence of dupA gene and evaluate the association among dupA and other virulence factors including cagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method. Results Patients with gastritis tested positive for H. pylori more frequently. The dupA gene was detected in 41.5% of them (85/205); cagA gene was found in 98 isolates (47.8%) and vacA genotype s1/m1 in 50.2%, s1/m2 in 8.3%, s2/m2 in 36.6%, s2/m1 in 0.5% and s1/s2/m1/m2 in 4.4%. We also verified a significant association between cagA and dupA genes [p = 0.0003, relative risk (RR) 1.73 and confidence interval [CI] = 1.3–2.3]. The genotypes s1/m1 were also associated with dupA gene (p = 0.0001, RR: 1.72 and CI: 1.3–2.2). The same associations were found when analyzing pediatric and adult groups of patients individually. Conclusion Ours results suggest that dupA is highly frequent in Brazilian patients and is associated with cagA gene and vacA s1/m1 genotype, and it may be considered an important virulence factor in the development of gastric diseases in adults or children.