• CagA
• Gastric cancer (GC)
• Helicobacter pylori (H. pylori)
• homologous-recombination genes (HR genes)
• virulence factors

• Gastric cancer
• Helicobacter pylori
• Infection
• Meta-analysis
• Prevalence
• Systematic review

• Humans
• Stomach Neoplasms/epidemiology
• Helicobacter pylori
• Prevalence
• Retrospective Studies
• Africa

• CagL polymorphisms
• CagLHM
• Helicobacter pylori
• non-ulcer dyspepsia
• peptic ulcer

Gastric cancer is the fifth most common malignancy and third leading cancer-related cause of death worldwide. Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3% of the world’s population and represents the main risk factor for the onset of gastric neoplasms. CagA is the most important virulence factor in H. pylori, and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions. Upon translocation and tyrosine phosphorylation, CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways, thereby disrupting cell proliferation, differentiation and apoptosis. All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes. In this sense, once gastric cancer sets in, its perpetuation is independent of the presence of the oncoprotein, characterizing a “hit-and-run” carcinogenic mechanism. Therefore, this review aims to describe H. pylori- and CagA-related oncogenic mechanisms, to update readers and discuss the novelties and perspectives in this field.

• Helicobacter pylori
• Virulence factors
• CagA
• Gastric cancer
• EPIYA motifs
• Hit-and-run carcinogenesis

• Chronic atrophic gastritis
• Helicobacter pylori
• management
• pathogenesis
• reversibility

• Gastritis/complications
• Gastritis/microbiology
• Gastritis, Atrophic/microbiology
• Helicobacter Infections/complications
• Helicobacter Infections/drug therapy
• Helicobacter Infections/microbiology
• Helicobacter pylori
• Humans
• Metaplasia/complications
• Stomach Neoplasms

Background: In Arizona Helicobacter pylori prevalence of infection among Navajo adults is about 62% and gastric cancer incidence rate is 3–4 times higher than that of the non-Hispanic White population. Aim: The aim of this study was to estimate the prevalence of specific H. pylori virulence factors (cagA and vacA) among Navajo patients undergoing and their association with gastric disease. Methods: Virulence genes, cagA and vacA, in H. pylori were investigated in gastric biopsies from 96 Navajo patients over age 18 who were undergoing esophagogastroduodenoscopy. Biopsies from the antrum and fundus were used for molecular characterization to determine cagA type and number of EPIYA motifs and presence of alleles in the signal (s) and medium (m) regions of the vacA gene. Results: H. pylori infection was found in 22.9% of the biopsy samples. The cagA gene amplified in 57.6% of samples and showed a predominant “Western cagA” type, with the EPIYA-ABC motif (45.4%), most prevalent. The vacA allele s1bm1 was the most prevalent (54.5%). Conclusions: H. pylori genotypes were predominantly cagA Western-type and ABC EPIYA motifs. The vacA s1bm1 genotype was the most prevalent and seemed to be associated with gastritis. American Indian/Alaska Native populations are at higher risk for gastric cancer. It is important to identify genotypes of H. pylori and virulence factors involved in the high prevalence of H. pylori and associated disease among the Navajo population.

• EPIYA-C motif
• Helicobacter pylori
• cagA
• geographic diversity
• polymorphism

Background: Helicobacter pylori (Hp) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the Hp virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells. However, CagA differs considerably in EPIYA motifs, whose functions have been well characterized in epithelial cells. Since CagA is fragmented in immune cells, different CagA variants may exhibit undetected functions in B cells. Methods: B cells were infected with Hp isolates and isogenic mutants expressing different CagA EPIYA variants. CagA translocation and tyrosine phosphorylation were investigated by Western blotting. Apoptosis was analyzed by flow cytometry and metabolic activity was detected by an MTT assay. Results: Isogenic CagA EPIYA variants are equally well translocated into B cells, followed by tyrosine phosphorylation and cleavage. B cell apoptosis was induced in a CagA-independent manner. However, variants containing at least one EPIYA-C motif affected metabolic activity independently of phosphorylation or multiplication of EPIYA-C motifs. Conclusions: The diverse structure of CagA regulates B cell physiology, whereas B cell survival is independent of CagA.

• B cells
• CagA
• EPIYA motifs
• Helicobacter pylori

• Cytotoxins/genetics
• Cytotoxins/metabolism
• Gene Expression Regulation, Bacterial
• Gene Expression Regulation, Neoplastic
• Genetic Variation
• Genotype
• Helicobacter Infections/metabolism
• Helicobacter Infections/physiopathology
• Helicobacter pylori/genetics
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions/genetics
• Humans
• Lymphoma, B-Cell, Marginal Zone/metabolism
• Lymphoma, B-Cell, Marginal Zone/physiopathology
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/physiopathology

Gastric cancer (GC) is one of the leading causes of morbidity and mortality worldwide. The onset and progression of gastric cancer are attributed to numerous triggers, these triggers may be infection of the gastric epithelium by Helicobacter pylori (H. pylori), or by Epstein-Barr virus (EBV). Both agents can establish a lifelong persistent infection in the host, leading to chronic inflammation, which also contributes to cancer development. Objective: The objective of this study is to present the status of co-infection with H. pylori and EBV and the risk of developing adenocarcinoma at an early age in the population of Grand Casablanca.

In this study, 100 gastric tissue samples from patients with gastric cancer were examined for detection of H. pylori and EBV in tumor tissue using PCR techniques, and the clinical relevance was statistically analyzed.

Results revealed an individual Epstein-Barr virus (EBV) infection observed in (40 %) of gastric carcinoma cases. Furthermore, the frequency of EBV infection was significantly different with intestinal and diffuse gastric cancer types [15 % vs. 85 %; <0.05]. The prevalence of individual H. pylori infections was 34 %, while the frequency of co-infection was 16 %. Moreover, no significant association was found between co-infection and sex, tumor grade, stage, and lymph node metastasis, but there was a significant association between co-infection and the age of GC patients.

Thus understanding the status of co-infection could clarify the process of gastric carcinogenesis, and application of this knowledge for clinical purposes could facilitate diagnosis, risk management, and prevention.

Determination of the frequency of H. pylori and EBV infections

• Age
• Co-infection
• Epstein-barr virus
• Gastric cancer
• Helicobacter pylori

• Copy number
• H. pylori
• Heterogeneity
• Motif
• cagA

• Helicobacter pylori
• Iran
• cagA genotypes
• gastric cancer
• peptic ulcer

• Amino Acid Motifs
• Amino Acid Sequence
• Antigens, Bacterial/chemistry
• Antigens, Bacterial/metabolism
• Bacterial Proteins/chemistry
• Bacterial Proteins/metabolism
• Biopsy
• Ghana
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Helicobacter pylori/physiology
• Humans
• Phosphorylation
• RNA, Ribosomal, 16S/genetics
• Stomach/microbiology
• Stomach/pathology
• Structure-Activity Relationship
• Tyrosine/metabolism

• Wellcome Trust

• CagA
• CagA-EPIYA-C
• CagE
• Gastric pathologies
• Helicobacter pylori

• CagA
• Duodenal ulcer
• EPIYA
• Gastric cancer
• Helicobacter pylori
• Human leukocyte antigen

• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• HLA Antigens
• Helicobacter Infections
• Helicobacter pylori/genetics
• Humans
• Polymorphism, Genetic

• EPIYA motifs
• H. pylori
• gastric histopathological lesions
• vacA

• bacterial effector proteins
• drug repurposing
• host-directed therapy
• motif mimicry
• short linear motifs
• tyrosine kinase inhibitor (TKI)

• Adult
• Aged
• Amino Acid Motifs/genetics
• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• Colombia/epidemiology
• DNA, Bacterial/genetics
• Diagnostic Tests, Routine/standards
• Dyspepsia/microbiology
• Female
• Genes, Bacterial/genetics
• Genotype
• Helicobacter Infections/diagnosis
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Humans
• Male
• Middle Aged
• Polymerase Chain Reaction/standards
• Repetitive Sequences, Nucleic Acid/genetics
• Sequence Analysis, DNA/standards

• Pontificia Universidad Javeriana

There are controversies on the causal role of H. pylori in duodenal ulceration. Helicobacter pylori are curved gram-negative microaerophilic bacteria found at the layer of gastric mucous or adherent to the epithelial lining of the stomach. It’s a public health significance bacteria starting from discovery, and the prevalence and severity of the infection varies considerably among populations. H. pylori are a risk for various diseases, while the extent of host response like gastric inflammation and the amount of acid secretion by parietal cells affects the outcome of infection.

Relevant literature were searched from databases such as Google Scholar, PubMed, Hinari, Web of Science, Scopus, and Science Direct.

The review evidence supports a strong causal relation between H. pylori infection and duodenal ulcer, as patients are more likely to be infected by virulent strains which later cause duodenal ulceration. Thus, eradication of H. pylori infection decreases the incidence of duodenal ulcers, and prevents its recurrence by reducing both basal gastrin release and acid secretion without affecting parietal cell sensitivity. On the other hand, some studies show that H. pylori infection is not associated with the development of duodenal ulcers and such a lack of association revealed that duodenal ulceration has different pathogenesis.

Despite controversies observed in the causal role of H. pylori to duodenal ulceration by various studies, Hill criteria of causation proved the presence of a causal relation between H. pylori infection and duodenal ulcers. Other factors are also responsible for the development of duodenal ulcers and such factors are responsible for the differences in the prevalence of the diseases.

• H. Pylori
• causation
• controversies
• duodenal ulcer

Helicobacter pylori infection has been identified as a major cause of peptic ulcer diseases, including gastric and duodenal ulcers, gastritis, chronic and gastric carcinoma, and even gastric lymphoma. In vitro studies using Western blotting analysis, hemagglutination test, adherence inhibition assays, and immunocytochemical staining revealed that the 49.6-kDa subunit pili protein of H. pylori was considered an immunogenic protein. This study aimed to develop a serological diagnostic test using 49.6 kDa for detecting antibodies against H. pylori proteins in an early phase of the infection.

An in-house immunochromatographic test (ICT) kit was developed and used to test a panel of sera sample obtained from a randomly selected symptomatic patient, in which 40 sera were H. pylori positive and 40 sera were H. pylori negative.

The results showed that ICT with 49.6 kDa as an antigen was highly sensitive and specific for detecting anti-H. pylori immunoglobulin G antibodies in human serum, with a high negative predictive value.

The developed test could be used to exclude H. pylori infection in symptomatic patients.

• 49.6-kDa pili protein
• Helicobacter pylori
• immunochromatographic test

• CagA
• Helicobacter pylori
• Mongolia
• VacA
• gastric cancer
• genotyping

• Gastric cancer
• Gene polymorphism
• Helicobacter pylori
• Inflammation
• SNP

To correlate Helicobacter pylori (H. pylori), Epstein-Barr virus (EBV) and human papillomavirus (HPV) with gastric cancer (GC) cases in Pará State, Brazil.

Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eber1 RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.

The majority of the 302 samples analyzed were obtained from men (65%) aged 55 years or older (67%) and were classified as the intestinal subtype (55%). All three pathogens were found in the samples analyzed in the present study (H. pylori: 87%, EBV: 20%, HPV: 3%). Overall, 78% of the H. pylori-positive (H. pylori⁺) samples were cagA+ (H. pylori-cagA⁺), and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA⁺ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.

HPV was not involved in gastric tumorigenesis. Prophylactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

• Gastric cancer
• Gastric adenocarcinomas
• Microorganisms
• Helicobacter pylori
• cagA
• Epstein-Barr virus
• Human papillomavirus

• Adenocarcinoma/epidemiology
• Adenocarcinoma/microbiology
• Adenocarcinoma/pathology
• Adult
• Aged
• Aged, 80 and over
• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• Brazil/epidemiology
• Coinfection/epidemiology
• Coinfection/microbiology
• DNA, Bacterial/isolation & purification
• DNA, Viral/isolation & purification
• Epstein-Barr Virus Infections/epidemiology
• Epstein-Barr Virus Infections/virology
• Female
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Herpesvirus 4, Human/genetics
• Herpesvirus 4, Human/isolation & purification
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Papillomaviridae/genetics
• Papillomaviridae/isolation & purification
• Papillomavirus Infections/epidemiology
• Papillomavirus Infections/virology
• Stomach/microbiology
• Stomach/pathology
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA’s translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the phosphatidylserine and the docking of three mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA–Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score; mutations in this position were evaluated to observe the differences in intermolecular forces for the CagA–Phosphatidylserine complex. We evaluated the docking of three mutations: K636A, K636R and K636N. The crystal and mutation models presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG (χ2(1)=93.82, p-value <2.2×10−16) and the H-bonds (χ2(1)=91.93, p-value <2.2×10−16). Overall, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA–Phosphatidylserine complex interaction.

• CagA
• conservation N-terminal CagA
• homology modeling
• molecular docking
• phosphatidylserine
• phosphatidylserine mutations

• EPIYA motif
• Gastric cancer
• H. pylori infection
• cagA

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Motifs
• Amino Acid Sequence
• Antigens, Bacterial/chemistry
• Antigens, Bacterial/genetics
• Bacterial Proteins/chemistry
• Bacterial Proteins/genetics
• Biopsy
• Female
• Gastritis/diagnosis
• Gastritis/epidemiology
• Gastritis/microbiology
• Genetic Variation
• Genotype
• Helicobacter Infections/diagnosis
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Humans
• Male
• Middle Aged
• Morocco/epidemiology
• Polymorphism, Genetic
• Young Adult

The Helicobacter pylori (H. pylori) infection is a determinant factor in gastric cancer (GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin (IL)-1β, IL-1Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxin-associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.

• Helicobacter pylori
• Virulence factors
• Cytokines
• Gene polymorphisms
• Gastric cancer

• Cluspro
• FoldX
• Gromacs
• Helicobacter pylori CagA
• Intramolecular Energies
• Molecular modeling
• PIC

• Helicobacter pylori
• Myanmar
• cagA

• 3' Flanking Region/genetics
• Adult
• Antigens, Bacterial/analysis
• Antigens, Bacterial/genetics
• Bacterial Proteins/analysis
• Bacterial Proteins/genetics
• Female
• Gastritis/microbiology
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Humans
• Incidence
• Intestines/microbiology
• Intestines/pathology
• Male
• Metaplasia
• Middle Aged
• Myanmar/epidemiology
• Polymerase Chain Reaction
• Pyloric Antrum/microbiology
• Sequence Analysis, DNA
• Stomach Neoplasms/microbiology

• R01 DK062813 NIDDK NIH HHS

• epiya
• gastric diseases
• helicobacter pylori

• Antigens, Bacterial/genetics
• Antigens, Bacterial/metabolism
• Bacterial Proteins/genetics
• Bacterial Proteins/metabolism
• Humans
• Peptic Ulcer/epidemiology
• Peptic Ulcer/metabolism
• Phosphorylation
• Risk
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/metabolism

• Bacterial diversity
• Carcinogenesis
• Helicobacter pylori
• Host susceptibility

• Animals
• Antigens, Bacterial/genetics
• Bacterial Outer Membrane Proteins
• Bacterial Proteins/genetics
• Biomarkers, Tumor/metabolism
• DNA Damage
• DNA Repair
• Early Detection of Cancer
• Gastritis/microbiology
• Genetic Predisposition to Disease
• Helicobacter Infections/complications
• Helicobacter pylori
• Host-Pathogen Interactions
• Humans
• Immune System
• Inflammation
• Mice
• Neoplasm Metastasis
• Polymorphism, Genetic
• Receptors, Pattern Recognition
• Stomach/microbiology
• Stomach Neoplasms/complications
• Stomach Neoplasms/microbiology
• Treatment Outcome
• Virulence
• Virulence Factors

Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori. Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8) induction. Sequence analysis of the repeat region revealed three cagA homologous areas (CHAs) within the cagA repeats. Of these, CHA-ud flanked each of the cagA copies and is likely important for the dynamic variation of cagA copy numbers. Analysis of a large panel of clinical isolates showed that 7.5% of H. pylori strains isolated in the United States harbored multiple cagA repeats, while none of the tested Korean isolates carried more than one copy of cagA. Finally, H. pylori strains carrying multiple cagA copies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction of cagA copy numbers may serve as a novel mechanism by which H. pylori modulates gastric disease development.

Severity of H. pylori-associated disease is directly associated with carriage of the CagA toxin. Though the sequences of the CagA protein can differ across strains, previous analyses showed that virtually all H. pylori strains carry one or no copies of cagA. This study showed that H. pylori can carry multiple tandem copies of cagA that can change dynamically. Isolates harboring more cagA copies produced more CagA, thus enhancing toxicity to host cells. Analysis of 314 H. pylori clinical strains isolated from patients in South Korea and the United States showed that 7.5% of clinical strains in the United States carried multiple cagA copies whereas none of the South Korean strains did. This study demonstrated a novel molecular mechanism by which H. pylori dynamically modulates cagA copy number, which affects CagA expression and activity and may impact downstream development of gastric disease.

• gastric cancer
• helicobacter pylori
• caga
• epiya motif
• cm motif
• hit-and-run carcinogenesis

• Amino Acid Motifs
• Animals
• Antigens, Bacterial/chemistry
• Antigens, Bacterial/genetics
• Antigens, Bacterial/metabolism
• Bacterial Proteins/chemistry
• Bacterial Proteins/genetics
• Bacterial Proteins/metabolism
• Carcinogenesis
• Helicobacter pylori/metabolism
• Helicobacter pylori/physiology
• Humans
• Neoplasms/microbiology
• Neoplasms/pathology
• Type IV Secretion Systems/metabolism

Infection with Helicobacter pylori (H. pylori) has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• DNA Fragmentation
• Female
• Gastric Mucosa/microbiology
• Gastritis/microbiology
• Genotype
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Humans
• Male
• Middle Aged
• Phenotype
• Protein Processing, Post-Translational/genetics
• Stomach Neoplasms/microbiology
• Young Adult

• CagA
• CagA gene polymorphism
• Gastric carcinoma
• Gene methylation
• Haplotype
• Helicobacter pylori infection
• Human gene mutation
• Inflammatory cytokine

Infection with cagA-positive Helicobacter pylori is critically associated with the development of gastric cancer. The cagA-encoded CagA is delivered into gastric epithelial cells via type IV secretion, where it interacts with and thereby deregulates the pro-oncogenic phosphatase SHP2. East Asian CagA and Western CagA are two major CagA species produced by H. pylori circulating in East Asian countries and in the rest of the world, respectively. The SHP2 binding site of Western CagA, termed the EPIYA-C segment, variably duplicates and infection with H. pylori carrying Western CagA with multiple EPIYA-C segments is a distinct risk factor of gastric cancer. Here we show that duplication of EPIYA-C from one to two or more increases SHP2 binding of Western CagA by more than one hundredfold. Based on the decisive difference in SHP2 binding, Western CagA can be divided into two types: type I CagA carrying a single EPIYA-C segment and type II CagA carrying multiple EPIYA-C segments. Gastric epithelial cells expressing type II CagA acquire the ability to invade extracellular matrices, a malignant cellular trait associated with deregulated SHP2. A big leap in SHP2 binding activity may therefore provide molecular basis that makes type II Western CagA a distinct gastric cancer risk.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Motifs
• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• Case-Control Studies
• DNA, Bacterial/chemistry
• DNA, Bacterial/genetics
• Female
• Geography
• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/genetics
• Helicobacter pylori/isolation & purification
• Humans
• Male
• Middle Aged
• Polymerase Chain Reaction
• Repetitive Sequences, Amino Acid
• Risk Assessment
• Sequence Analysis, DNA
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology
• Turkey/epidemiology
• Young Adult

• gastric cancer
• stat3 gene polymorphism
• stat3 rs744166
• helicobacter pylori
• caga
• epiya-c segments

• Adult
• Antigens, Bacterial/blood
• Antigens, Bacterial/genetics
• Bacterial Proteins/blood
• Bacterial Proteins/genetics
• Biomarkers
• Female
• Gastritis/genetics
• Gastritis/microbiology
• Genetic Association Studies
• Helicobacter Infections/blood
• Helicobacter Infections/genetics
• Helicobacter Infections/microbiology
• Helicobacter pylori/metabolism
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors
• STAT3 Transcription Factor/genetics
• STAT3 Transcription Factor/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology

• Gastric Cancer
• Helicobacter pylori
• cagA motifs
• dupA
• gastrointestinal disease

• CagA
• EPIYA motif
• Gastric carcinogenesis
• Helicobacter pylori
• cell signaling
• comparative study

• Antigens, Bacterial/metabolism
• Bacterial Proteins/metabolism
• Cell Line, Tumor
• Gene Expression Profiling
• Helicobacter pylori/pathogenicity
• Helicobacter pylori/physiology
• Host-Pathogen Interactions
• Humans
• Oncogene Proteins/metabolism
• Real-Time Polymerase Chain Reaction
• Signal Transduction/drug effects
• Stomach Neoplasms/physiopathology
• Transcription, Genetic/drug effects
• Transfection

Gastric cancer is one of the most common malignancies worldwide, and Helicobacter pylori (H. pylori) infection is the most important risk factor. More than 50% of the world population is infected by H. pylori, but less than 2% develop gastric cancer. Other risk factors like host and environmental factors also play a role in the occurrence of gastric cancer. The pathogenesis of gastric cancer is a multi-factorial and multi-step process, and its outcome is influenced by a combination of host, bacterial, and environmental factors.

• Gastric cancer
• Helicobacter pylori
• MicroRNA
• Environment