Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of cytokine genotypes with gastric carcinoma (GC) may be influenced by environmental factors and varies among different populations. Few studies have addressed the impact of different cytokine genotypes on the development and progression of GC. We analyzed 11 functional polymorphisms in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-4 and IL-10 genes in 220 Taiwanese Chinese with GC and in 230 healthy controls. The risk of genotypes was adjusted with confounding environmental risks. Our results revealed that the frequency of Helicobacter pylori infection [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.19-2.56], cigarette smoking (OR 2.02, 95% CI 1.38-2.95) and high IL-10 producer genotype (OR 2.67, 95% CI 1.29-5.50) was significantly increased in the entire GC patients. Among different subtypes of GC, a higher risk of developing diffuse type (OR 1.64, 95% CI 1.01-2.67) or cardia cancer (OR 2.44, 95% CI 1.13-2.67) was observed for the CT/CC genotype of IL-4 at the position -590, whereas the high IL-10 producer genotype was significantly linked with the risk of cardia cancer (OR 3.21, 95% CI 1.06-9.73) or advanced stage (OR 2.29, 95% CI 1.12-4.64). No association was noted between GC and controls in the distribution of IL-1 and TNF-alpha genotypes. Logistic regression analyses revealed that H. pylori infection (OR 1.7, 95% CI 1.14-2.52), cigarette smoking (OR 1.87, 95% CI 1.27--2.96) and IL-10 genotype (OR 2.54, 95% CI 1.24-5.61) are independent risks for GC. Independent effects of IL-10 genotype, H. pylori infection and cigarette smoking indicate that carcinogenesis of GC is influenced by a variety of host and environmental factors.
 ...
PMID:Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese. 1259 17

Primary non-Hodgkin's lymphomas of the stomach are associated with Helicobacter pylori infection. We analyzed gastric lymphoma onset data with respect to prior H. pylori infections based on the multistage theory of carcinogenesis. This theory provides a link between epidemiological data and biological processes. The study involved 133 patients, aged 29-75 years, diagnosed with marginal zone B-cell lymphoma (MZBL) and diffuse large cell B-cell lymphoma (DLBL). A 2-parametric Weibull model was applied to MZBL and DLBL onset data. Median age of diagnosis of MZBL (DLBL) was 59 years (55 years) in males and 65.5 years (64 years) in females. Infection with H. pylori was found in 81.3% (59.5%) of the patients diagnosed with MZBL (DLBL). Lymphoma latency data were fitted to Weibull distributions with a shape parameter of 5.7 for MZBL cases and 4.2 for DLBL. The shape parameter that indicates the number of steps in carcinogenesis was approximately independent of the status of infection with H. pylori in DLBL in contrast to MZBL. It was shown that gastric lymphoma onset data can be described by Weibull distribution functions. The findings support the hypothesis that MZBL and DLBL have different lines of development. There is indication of stronger antigen dependency in the carcinogenesis of MZBL in comparison to DLBL.
 ...
PMID:Helicobacter pylori and carcinogenesis of gastric B-cell lymphomas. 1259 22

An excess of stomach cancer among workers has been observed and it could be argued that men whose occupation involves heavy work eat more and are consequently exposed to a greater quantity of carcinogens in their food. Working under conditions of heat stress greatly increases a worker's salt excretion by as much as 0.1-15.0 g through sweating during one shift of work. Workers exposed to heat stress had consumed daily as much as from 13.0 to 38.0 g of salt, which is much higher than the safe level of 6 g/person/day recommended by the WHO, to keep a balance of salt in the body. Because salt strongly enhances and promotes chemical gastric carcinogenesis and Helicobacter pylori infection in both humans and animals, there is an association between work, salt intake, and the development of stomach cancer among workers in particular and in humans in general.
 ...
PMID:Work, salt intake and the development of stomach cancer. 1261 21

Helicobacter pylori infection is associated with increased gastric epithelial cell turnover and is a risk factor for noncardia gastric cancer. H. pylori reduces the expression of p27 protein, a cyclin-dependent kinase inhibitor of the G(1) to S-phase cell cycle transition and gastric tumor suppressor gene. Although cell cycle dysregulation associated with decreased p27 may contribute to gastric carcinogenesis, how H. pylori reduces p27 in gastric epithelial cells remains unknown. In the present study, we investigated the mechanisms of the p27 decrease, using AGS and MKN28 gastric epithelial cells cocultured with H. pylori strains under conditions of defined cell cycle distribution. The expression of p27 protein was reduced by H. pylori in a dose- and time-dependent manner. Northern blot and pulse-chase analyses revealed that this reduction was not regulated at a transcriptional level but by accelerated p27 degradation via a proteasome-dependent pathway. Despite up-regulation of the proteasome-dependent degradation of p27 protein, neither threonine 187-phosphorylated p27 nor skp2 (the ubiquitin ligase for p27) were increased. Furthermore, H. pylori impaired p27 ubiquitination and did not increase global proteasomal function. These results indicate that H. pylori increases the degradation of p27 through a proteasomal pathway distinct from the physiological pathway that degrades p27 during cell cycle progression. Putative virulence genes of H. pylori (cagA, cagE, or vacA) played no role in reducing p27 expression. Increased degradation of p27 by H. pylori through a proteasome-dependent, ubiquitin-independent pathway may contribute to the increased risk of gastric cancer associated with chronic H. pylori infection.
 ...
PMID:Helicobacter pylori increases proteasome-mediated degradation of p27(kip1) in gastric epithelial cells. 1290 57

The etiology of gastric cancer (GC) is multifactorial, and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. This article reviews the considerable progress that has been achieved in understanding the genetics of GC. The genetic effects consist of inherited genetic factors that predispose to GC, and the genetic targets of neoplastic progression that confer altered growth capacity to neoplastic cells. Inherited genotypes include germline mutations of high-penetrance genes directly associated with hereditary GC syndromes and genetic polymorphisms that indirectly affect the susceptibility to GC after exposure to carcinogens or Helicobacter pylori infection. Based on accumulation of different oncogenes or tumor suppressor genes alterations, 2 broad classes of genetic pathways called suppressor and mutator phenotypes are defined that participate in the development and progression of GC. Examples of genes involved in pathogenesis of GC include p53, adenomatous polyposis coli (APC), beta-catenin, E-cadherin, transforming growth factor (TGF)-betaRII, and hMLH1. Delineating genes involved in different subtypes of GC can reflect the heterogeneity and biologic characteristics of GC. Elucidation of the role of inherited genotypes and genetic alterations at different stages of gastrocarcinogenesis may provide a more coherent picture of the mechanism of this devastating disease and facilitate the development of novel approaches to effective prevention and intervention. Advances in high throughput technologies and functional genomics have rapidly increased our understanding of gene structure and function and its role in disease.
 ...
PMID:Genetic alterations and polymorphisms in gastric cancer. 1451 82

Established risk factors for gastric cancer include a diet high in nitrate or nitrite and low in vitamin C and the presence of achlorhydria or hypochlorhydria. The aim of this study was to investigate the relationship between intragastric nitrite concentration and atrophic change of the stomach or gastric carcinogenesis in Japanese Helicobacter pylori-infected patients. Gastric juice pH, nitrite, and total vitamin C concentrations in gastric juice, serum pepsinogen I and II concentrations, and specific Helicobacter pylori antibody were analyzed. Intragastric total vitamin C concentration was decreased by Helicobacter pylori infection of the gastric mucosa and with progression of the atrophic grade. There was a significant positive correlation between atrophic grade and intragastric nitrite concentration. In conclusion, the levels of nitrite in gastric juice play a causal role in the development of cancer in Helicobacter pylori-associated atrophic gastric mucosa.
 ...
PMID:Does intragastric nitrite concentration reflect gastric carcinogenesis in Japanese Helicobacter pylori-infected patients? 1456 Sep 92

Although a number of epidemiological, biological and clinical studies have been published, the effective role of Helicobacter pylori infection in gastric carcinogenesis remains unclear. In the present work we retrospectively compared Helicobacter infection rate, by means of histologic examination of gastric bioptic samples, in 70 patients affected by gastric carcinoma, 70 with ulcerous disease and 70 with non-ulcerous dyspepsia. The analysis was carried out by a single pathologist. The differences between the 3 groups were not statistically significant. From our present and previously reported data, the Helicobacter infection cannot be considered per se a significant risk factor for malignant gastric disease and further studies are needed to evaluate the role of Helicobacter infection in the development of some preneoplastic conditions such as chronic atrophic gastritis and intestinal metaplasia.
 ...
PMID:Retrospective histologic comparison of Helicobacter pylori infection in gastric carcinoma, ulcerous disease and non-ulcerous dyspepsia. 1458 92

Hemigastrectomy for benign disease and Helicobacter pylori infection are risk conditions for the development of gastric cancer. Aim of the study was to compare gastric histology and precursor lesions of malignancy in these two conditions. The hemigastrectomy group included 351 consecutively endoscoped subjects operated for gastroduodenal benign disease. Six to ten biopsy specimens were routinely taken from the residual gastric mucosa. The intact stomach group included 2097 consecutively endoscoped symptomatic subjects, who did not receive eradication therapy against H. pylori. The histological findings were classified as normal mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization. The age over fifty was a significant risk factor for the occurrence of IM (OR 2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or = 0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or = 0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P < or = 0.001). Both in males and females the risk for CNAG was significantly higher in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000). Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82, P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp-positive individuals evidenced a significant risk for metaplastic mucosal changes (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those with a longer postoperative follow up endoscopy presented an increased risk for CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000). CNAG and IM were the most frequently observed mucosal lesions both in subjects operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and 3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H. pylori infection may induce an increased incidence for histological precursor lesions for gastric malignancy and suggest that carcinogenesis in a resected stomach may be different from that in the intact stomach.
 ...
PMID:Cancer precursor lesions in intact stomach Helicobacter pylori gastritis and in resected stomach gastritis. 1458 93

Promoter methylation of death-associated protein kinase (DAPK) occurs frequently in cancer cells, which results in the decreased transcription of DAPK. Although promoter methylation of DAPK has been previously reported, it has not been explored in the surrounding normal tissues of gastric cancer patients. Herein we have examined whether the promoter methylation of DAPK gene or down-modulation of DAPK is associated with gastric atrophy. Thirty-nine samples of surgically resected gastric carcinomas and corresponding non-tumorous tissues were studied. Methylation-specific polymerase chain reaction was performed to test DAPK promoter methylation. We evaluated the expression level of DAPK protein in normal and atrophic gastric tissue by both Western blot analysis and immunohistochemical staining. Significant correlation was not observed between methylation and an advanced pathological stage of tumor. No association was found between promoter methylation of DAPK and Helicobacter pylori infection, whereas a close association was observed with the presence of gastric atrophy and DAPK promoter methylation (P=0.015). The level of DAPK protein expression was significantly low in atrophic gastritis compared with those without atrophy (P=0.003). Collectively, DAPK promoter methylation and down-regulation is tightly associated with gastric atrophy, which often contributes to the preneoplastic changes in gastric carcinogenesis.
 ...
PMID:Promoter methylation and down-regulation of DAPK is associated with gastric atrophy. 1461 52

Despite decreasing incidence during the last 50 years, gastric cancer still ranks as one of the most frequent cancers. A multifactorial model of human gastric carcinogenesis is currently accepted in which different dietary and nondietary factors, including genetic susceptibility of the host and Helicobacter pylori infection are involved at different stages in the cancer process. On the molecular level, at least two phenotypes, associated with distinct pathways of genome destabilization, have been identified. However, applying new technologies such as cDNA microarrays a new era in the analysis of molecular markers has started. This molecular technology may open the path towards novel treatment modalities, i.e. gene therapy. Epidemiological, biological, and molecular genetic studies have also implicated the role of H. pylori in lymphomagenesis. Knowledge of pathogenesis and therapy is increasing while good epidemiological data are rare. Many studies have demonstrated that MALT-type lymphomas develop along two different pathways: t(11;18)-positive cases, and t(11;18)-negative cases. Meanwhile, a third translocation could be detected, the t(14;18), opening the discussion of a possible third pathway of lymphoma development.
 ...
PMID:Helicobacter pylori and gastric malignancies. 1461 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>