Influence of Helicobacter pylori infection on the expression of MLH1 and MGMT in patients with chronic gastritis and gastric cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Helicobacter pylori infection on IL-8, IL-1 and COX-2 expression in patients with chronic gastritis and gastric cancer

Objective. Helicobacter pylori infection is related to gastric cancer development, and chronic inflammation is presumed to be the main cause. The aim of the present study was to evaluate the influence of H. pylori cagA, vacA, iceA, and babA genotypes on COX-2, IL-1, and IL-8 expression. Material and methods. of the 217 patients included in the study, 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 values were determined by quantitative real-time PCR and immunohistochemistry. Results. An association was found between the infection with cagA, vacA s1m1 strains and gastric cancer development. Regarding the 3' region of the cagA gene, we also found an association between the infection with cagA EPIYA-ABCCC strains and clinical outcome. Higher levels of IL-8, IL-1, and COX-2 were detected in gastric mucosa from infected patients with chronic gastritis, and they were also associated with the infection by cagA, vacA s1m1 strains. The IL-8 and IL-1 levels decrease significantly from chronic gastritis to gastric cancer, while the relative expression remained unaltered when COX-2 expression was analyzed among patients with gastritis and cancer. Conclusions. Since inflammatory response to H. pylori infection plays an important role in cellular proliferation and gastric mucosal damage, the up-regulation of IL-1, IL-8, and COX-2 in patients with chronic gastritis has an important clinical implication in gastric carcinogenesis.

Effects of Helicobacter pylori Infection on the Expressions of Bax and Bcl-2 in Patients with Chronic Gastritis and Gastric Cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of TERT in precancerous gastric lesions compared to gastric cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-beta pro-inflammatory cytokine is not

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer

Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of ancuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations. (C) 2004 Elsevier B.V. All rights reserved.

Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and gastric cancer

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Inactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype

Objective: We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by promoter methylation and its relationship with the infection by different Helicobacter pylori strains in gastric cancer. Methods: DNA extracted from 76 H. pylori-positive gastric tumor samples was available for promoter methylation identification by methylation-specific PCR and H. pylori subtyping by PCR. Immunohistochemistry was used to determine COX-2, p16(INK4A) and HMLH1 expression. Results: A strong negative correlation was found between the expression of these markers and the presence of promoter methylation in their genes. Among cardia tumors, negativity of p16(INK4A) was a significant finding. on the other hand, in noncardia tumors, the histological subtypes had different gene expression patterns. In the intestinal subtype, a significant finding was HMLH1 inactivation by methylation, while in the diffuse subtype, CDKN2A inactivation by methylation was the significant finding. Tumors with methylated COX-2 and HMLH1 genes were associated with H. pylori vac A s1 (p = 0.025 and 0.047, respectively), and the nonmethylated tumors were associated with the presence of the gene flaA. Conclusions: These data suggest that the inactivation of these genes by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the H. pylori genotype. Copyright (C) 2011 S. Karger AG, Basel

Endogenous carotenoid concentrations in cancerous and non-cancerous tissues of gastric cancer patients in Korea

Carotenoid concentrations were measured in serum and in both non-cancerous and cancerous gastric mucosal tissues of Korean patients with gastric cancer (n = 18). Carotenoids in serum and gastric tissue were extracted with chloroform/methanol (2:1), and measured using reverse-phase high-performance liquid chromatography with a C30 column. Cryptoxanthin and β-carotene were the major carotenoids in the Korean blood and they had a median ratio of non-cancerous tissue/serum levels which was less than 1.0. No significant differences of Cryptoxanthin and β-carotene levels were found between non-cancerous and cancerous tissues. After incubation of β-carotene with gastric tissue, significantly higher levels of β-carotene breakdown products were produced in the homogenates of cancerous tissue when compared with non-cancerous tissue. Lutein, zeaxanthin and α-carotene were the minor carotenoid constituents in the blood and their median ratio of non-cancerous tissue/serum levels was greater than 1.0. Cancerous tissue had significantly lower levels of lutein, zeaxanthin and α-carotene than did non-cancerous tissue. It appears that the increased breakdown of β-carotene and cryptoxanthin in cancerous tissue can be compensated for by an increased uptake of circulating carotenoids by cancerous tissue, whereas lutein, zeaxanthin and α-carotene levels in cancerous tissue are not able to be maintained.

GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)