Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Min mouse, which has a germ line mutation in 1 allele of the Apc tumor suppressor gene, is a model for the early steps in human colorectal cancer. Helicobacter pylori infection, a known risk factor for gastric cancer in humans, causes chronic inflammation and increased epithelial cell proliferation in the stomach. Infection with the bacterium Citrobacter rodentium is known to increase epithelial cell proliferation and to promote chemically initiated tumors in the colon of mice. Min mice infected with C. rodentium at 1 month of age were found to have a 4-fold increase in the number of colonic adenomas at 6 months of age, compared with uninfected Min mice. Most of the colonic adenomas in the infected Min mice were in the distal colon, where C. rodentium-induced hyperplasia occurs. These data demonstrate that bacterial infection promotes colon tumor formation in genetically susceptible mice.
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PMID:Bacterial infection promotes colon tumorigenesis in Apc(Min/+) mice. 1142 22

Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.
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PMID:CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma. 1253 60

Infection with Helicobacter pylori increases the risk of gastric cancer. One possible mechanism is the higher likelihood of malignant transformation due to inflammatory responses in the epithelium. An alternative explanation is that these inflammatory responses induce chronic gastritis associated with decreased acidity in the stomach, which in turn increases the endogenous formation of carcinogenic N-nitroso compounds. Inflammatory responses seem to trigger two different causal pathways: one for the diffuse type of gastric cancer and the other for the intestinal type. The striking geographic variability in intestinal gastric cancer can be explained by the synergistic interaction between H. pylori infection and dietary factors, such as intake of salt and ascorbic acid. Screening and eradication of this organism, together with appropriate dietary modifications, offer promise in countries with a high prevalence of H. pylori infection and high risk of gastric cancer, but the safety of such interventions needs to be ensured.
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PMID:Synergistic interaction between Helicobacter pylori gastritis and diet in gastric cancer. 1190

Infection with the gastric bacterium Helicobacter pylori (in particular infection with CagA-positive strains) and smoking have been identified as risk factors for the development of gastric cancer. Both risk factors are typically acquired early in life and prevail over decades if not for life. We assessed the individual and joint impact of both risk factors on gastric cancer risk in a population-based case-control study from Germany including 71 patients with histologically verified gastric cancer and 363 patients with colorectal cancer who served as controls. Information on smoking and potential confounding factors was collected by standardized interviews. H. pylori infection was measured serologically by immunoglobulin G antibody titers against H. pylori. In addition, antibodies against the CagA antigen were determined by Western blot. Twenty-seven percent of cases compared with 15% of controls were smokers, and 43% of cases compared with 23% of controls were infected with CagA-positive H. pylori strains. After control for potential confounders, the relative risk of gastric cancer was 2.6 (95% CI 1.2-5.7) for nonsmoking subjects with CagA-positive H. pylori infections and 7.2 (95% CI 2.2-23.6) for smoking subjects with CagA-positive H. pylori infections compared with subjects without these risk factors. The corresponding relative risks for noncardia gastric cancer were 6.1 ( 95% CI 2.3-16.5) and 16.6 (95% CI 4.3-64.2). We conclude that smoking subjects with CagA-positive H. pylori infections have a strongly increased risk of gastric cancer and may be an important group for targeting efforts of prevention and early detection.
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PMID:Risk of gastric cancer among smokers infected with Helicobacter pylori. 1192 May 98

The objective of this study was to evaluate the prevalence of antibodies to Helicobacter pylori CagA and VacA proteins and correlate this prevalence with gastric diseases in colonised Chileans. The study was performed in 418 adults colonised with H. pylori: 316 with gastroduodenal pathology (152 duodenal ulcer, 14 gastric cancer and 150 gastritis patients) and 102 asymptomatic subjects. Serum IgG antibodies to H. pylori were determined by enzyme immunoassay (EIA). Antibodies to VacA and CagA proteins were detected by Western blotting. In a subgroup of the patients, the vacuolating activity was determined by HeLa cell assay and the CagA product was confirmed by PCR assay. IgG antibodies to both VacA and CagA proteins of H. pylori were found in 270 (85%) of 316 colonised gastric patients and in 72 (71%) of 102 asymptomatic subjects. Colonisation with virulent strains was significantly higher among duodenal ulcer and gastric cancer patients than in gastritis patients or asymptomatic subjects. Infections with VacA+/ CagA+ H. pylori strains is common in Chile but, in contrast to some Asian countries, this phenotype was more prevalent in isolates from patients with more severe gastric pathologies.
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PMID:Prevalence of serum antibodies to Helicobacter pylori VacA and CagA and gastric diseases in Chile. 1192 34

Gastric carcinoma is thought to develop via the actions of inducers and promoters of carcinogenesis. Tryptophan in charred fish or animal meat, ultraviolet rays, and irradiation, which damage genes of normal cells, have long been regarded as inducers of carcinoma, and agents such as alcohol, tobacco, aflatoxin, and nitrosoamine as promoters, with tobacco having both activities. The interaction between these environmental factors, principally diet, and Helicobacter pylori (Hp) is important in the genesis of gastric carcinoma. In this report, the histopathological feature of the Hp gastritis-carcinoma sequence is outlined, and the pathological characteristics of gastroesophageal reflux disease (GERD) and endoscopically negative reflux disease (ENRD) and the risk factors for lower esophageal carcinoma after Hp eradicated status in particular are discussed regarding aspects of cell cycle-associated factors. We conclude that (1) Infection with Hp increases the risk of gastric cancer in two histological phenotypes (i.e., diffuse undifferentiated type and intestinal differentiated type). Excessive cell replication and interrupting the mucus secretion mechanism may result in a large proportion of cells with genetic abnormalities. (2) Genetic alterations in gastric carcinogenesis may differ from those in colonic carcinogenesis. (3) The degree of GERD in Japanese patients is milder than that in patients from Western countries, although the incidence of GERD increases the status after successful eradication of Hp. It is also possible that accumulation of genetic abnormalities increases the number of cardiac and lower esophageal cancers. Investigation of cell cycle factors in GERD including ENRD can be expected to reveal the risk of carcinogenesis.
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PMID:Pathological issues of gastric and lower esophageal cancer: helicobacter pylori infection and its eradication. 1210 62

Infection by Helicobacter pylori is recognized as a risk factor for gastric cancer and peptic ulcer disease. Venezuela has regions with different gastric cancer risks; the Andean region has the highest gastric cancer mortality in the country. We performed a cross-sectional study on 357 patients who underwent endoscopy attending 2 private (n = 76) and one public hospital in Caracas, Venezuela (n = 215), and one public hospital in the Andes (n = 66) to determine H. pylori infection (by a rapid biopsy urease test and histology). The proportion of infected patients in Caracas was significantly higher in public hospitals (72%) than in private hospitals (46%; P = 0.00001), and there was no significant variation the Andes and Caracas (P = 0.7001). When analyzing the data from the public hospital in Caracas, we found that the frequency of infected patients was significantly higher during the rain (96%) than during the dry months (70%, P = 0.00000001). Differences in prevalence of infection in symptomatic patients was not related to the risk of gastric cancer but to socioeconomic differences. Rain-dependent factors that may be exacerbating the clinical activity of nonulcer dyspepsia in people infected with H. pylori deserve further study.
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PMID:Short report: socioeconomic and seasonal variations of Helicobacter pylori infection in patients in Venezuela. 1213 67

Helicobacter pylori colonizes the gastric mucosa of more than half of all people worldwide and is the major cause of peptic ulcer disease and an early risk factor for gastric cancer, even though most infections are asymptomatic. Infection occurs preferentially in early childhood and once established tends to persist for years or decades. Much of the pathology H. pylori causes probably results from the host response to infection, which is affected by bacterial genotype, human host characteristics and environmental conditions. H. pylori is one of the most genetically diverse of bacterial species, with different genotypes predominating in different parts of the world. In particular, strains from India differ from those of Europe and East Asia in DNA sequence of several diagnostic gene segments. This outcome invites speculation about H. pylori origins and the possibility of Indian-specific genes that might be uncommon in Western strains. Much has been learned from H. pylori genome sequences, along with epidemiological, mutational, molecular and immunologic analyses. Candidate bacterial colonization and virulence genes and host responses are being identified, and the hypotheses being developed are amenable to tests in cell culture and animal models. These research efforts, many of which are collaborative and international, provide insights into mechanisms of establishment and persistence of H. pylori infection and virulence, and should lead to new, far more potent and cost effective anti-Helicobacter therapies or vaccines, and thereby major improvement in human health worldwide.
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PMID:Molecular & evolutionary genetics & drug resistance of the gastric pathogen, Helicobacter pylori. 1220 Nov 78

Helicobacter pylori infects over half the world's population and causes a wide range of diseases, including gastritis, peptic ulcer, and two forms of gastric cancer. H. pylori infection elicits a variety of phenotypic responses in cultured gastric epithelial cells, including the expression of proinflammatory genes and changes in the actin cytoskeleton. Both of these responses are mediated by the type IV secretion system (TFSS) encoded by the cag pathogenicity island (cag PAI). We used human cDNA microarrays to examine the temporal transcriptional profiles of gastric AGS cells infected with H. pylori strain G27 and a panel of isogenic mutants to dissect the contributions of various genes in the cag PAI. Infection with G27 induced expression of genes involved in the innate immune response, cell shape regulation, and signal transduction. A mutant lacking the cagA gene, which encodes an effector molecule secreted by the TFSS and required for the host cell cytoskeletal response, induced the expression of fewer cytoskeletal genes. A mutant lacking cagE, which encodes a structural component of the TFSS, failed to up-regulate a superset of host genes, including the cagA-dependent genes, and many of the immune response genes. A mutant lacking the entire cag PAI failed to induce both the cagE-dependent genes and several transiently expressed cagE independent genes. Host cell transcriptional profiling of infection with isogenic strains offered a detailed molecular picture of H. pylori infection and provided insight into potential targets of individual virulence determinants such as tyrosine kinase and Rho GTPase signaling molecules.
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PMID:Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. 1241 77

Infection with Helicobacter pylori (H. pylori), especially CagA+ strains, has been associated with an increased risk of noncardia gastric adenocarcinoma. The relationship with junctional cancer (adenocarcinomas of the esophagus and gastric cardia combined) has not been adequately investigated, although some studies have reported a reduced risk associated with H. pylori and CagA seroseropositivity. We investigated this question in a subset of cases and controls from a recently completed, large population-based case-control study of gastric and esophageal adenocarcinomas in Los Angeles County. Using established antigen-specific ELISAs, serum IgG antibodies to H. pylori whole-cell antigens (Helico-G) and CagA were measured in population controls (n = 356) and patients with incident esophageal adenocarcinoma (n = 80), gastric cardia cancer (n = 87) or distal gastric cancers (noncardia gastric adenocarcinoma) (n = 127). After controlling for demographic characteristics (age, gender, race, birthplace, education), smoking and body mass index, seropositivity for H. pylori was associated with a statistically significant increased risk of distal gastric cancer (adjusted odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.03, 3.32) but the risk of junctional cancer was not increased (adjusted OR = 1.26, 95% CI = 0.82, 1.94). The risk of junctional cancer was not changed when CagA and H. pylori were both considered, but the risk of distal gastric cancer was further increased. Subjects who were seropositive for both CagA and H. pylori compared to those who were seronegative for H. pylori showed a risk of 2.20 (95% CI = 1.13, 4.26) for distal gastric cancer and 0.86 (95% CI = 0.47, 1.59) for junctional cancer. Although tests for interaction between smoking and H. pylori were not statistically significant for junctional or distal gastric cancers, risk for both tumor types tended to be higher among current smokers who were also H. pylori seropositive. In conclusion, we find no evidence that infection with CagA+ strains of H. pylori reduces risk of esophageal and gastric cardia adenocarcinoma in this population. Our findings confirm the positive association between risk of distal gastric cancer and infection with H. pylori infection, especially CagA+ strains.
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PMID:Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus. 1251 4


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