Helicobacter pylori co-infection with Epstein-Barr virus and the risk of developing gastric adenocarcinoma at an early age: Observational study infectious agents and cancer.
Ontology highlight
ABSTRACT: Background
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.Methods
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
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.Conclusion
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.
SUBMITTER: Rihane FE
PROVIDER: S-EPMC8346356 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundHelicobacter pylori (H. pylori) and Epstein - Barr virus (EBV) plays a significant role in aggressive gastric cancer (GC). The investigation of genes associated with these pathogens and host kinases may be essential to understand the early and dynamic progression of GC.AimThe study aimed to demonstrate the coinfection of EBV and H. pylori in the AGS cells through morphological changes, expression of the kinase and the probable apoptotic pathways.MethodsGenomic DNA isolation of H. pylori and its characterization from clinical samples were performed. RT-qPCR of kinases was applied to scrutinize the gene expression of kinases in co-infected GC in a direct and indirect (separated through insert size 0.45 μm) H. pylori infection set up. Morphological changes in co-infected GC were quantified by measuring the tapering ends of gastric epithelial cells. Gene expression profiling of apoptotic genes was assessed through RT-qPCR.ResultsAn interleukin-2-inducible T-cell kinase (ITK) showed significant upregulation with indirect H. pylori infection. Moreover, Ephrin type-B receptor six precursors (EPHB6) and Tyrosine-protein kinase Fyn (FYN) showed significant upregulation with direct coinfection. The tapering ends in AGS cells were found to be extended after 12 h. A total of 24 kinase genes were selected, out of which EPHB6, ITK, FYN, and TYK2 showed high expression as early as 12 h. These kinases may lead to rapid morphological changes in co-infected gastric cells. Likewise, apoptotic gene expression such as APAF-1 and Bcl2 family genes such as BAD, BID, BIK, BIM, BAX, AND BAK were significantly down-regulated in co-infected AGS cells.ConclusionAll the experiments were performed with novel isolates of H. pylori isolated from central India, for the functional assessment of GC. The effect of coinfection with EBV was more profoundly observed on morphological changes in AGS cells at 12 h as quantified by measuring the tapering of ends. This study also identifies the kinase and apoptotic genes modulated in co-infected cells, through direct and indirect approaches. We report that ITK, EPHB6, TYK2, FYN kinase are enhanced, whereas apoptotic genes such as APAF-1, BIK, FASL, BAX are significantly down-regulated in AGS cells coinfected with EBV and H. pylori.
| S-EPMC7523314 | biostudies-literature
Project description:Background/aimsEpstein-Barr virus (EBV) and Helicobacter pylori (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS).MethodsOverall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively.ResultsEBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p<0.001). Multivariate analysis revealed that EBV infection alone (hazard ratio [HR], 0.362; 95% CI, 0.131 to 0.996; p=0.049) and lower third location (HR, 0.624; 95% CI, 0.413 to 0.943; p=0.025) were inversely correlated with overall survival. During median follow-up period of 72 months, overall survival rate was not significantly different between the EBV and HP coinfection group and others (97.6% vs 86.8%; log-rank p=0.144). In non-GCLS patients (n=920), overall survival rate was not significantly different between the EBV infection group and others (96.9% vs 86.4%; log-rank p=0.126).ConclusionsEBV and HP coinfection is not an independent prognostic factor for gastric cancer. EBV infection status, regardless of HP infection, affects the clinicopathologic features of all types of gastric cancer. However, it does not lead to a significant difference in overall survival of non-GCLS patients.
| S-EPMC9840931 | biostudies-literature
Project description:Epstein-Barr virus (EBV)-associated gastric cancer belongs to 1 of the 4 subtypes of gastric cancer and accounts for 10% of total gastric cancers. However, most cases of gastric cancer have a history of Helicobacter pylori infection. Therefore, we investigated the possibility that H. pylori infection promotes the development of EBV-associated gastric cancer. H. pylori was exposed to principal EBV receptor, CD21, negative gastric epithelial cells, and then infected with EBV recombinant expressing enhanced green fluorescent protein. Changes in EBV infectivity due to prior H. pylori exposure were analyzed using flow cytometry. The treatment of gastric epithelial cells with H. pylori increased the efficiency of EBV infection. An increase was also observed when CagA-deficient, VacA-deficient, and FlaA-deficient H. pylori strains were used, but not when cag pathogenicity island-deficient H. pylori was used. The treatment of epithelial cells with H. pylori induced the expression of accessory EBV receptors, EphA2 and NMHC-IIA, and increased the efficiency of EBV infection depending on their expression levels. When gastric epithelial cells were treated with EPHA2 or NMHC-IIA siRNA, EBV infection via H. pylori attachment was decreased. The adhesion of H. pylori induced the expression of accessory EBV receptors in gastric epithelial cells and increased the efficiency of EBV infection.
| S-EPMC8586688 | biostudies-literature
Project description:BackgroundChronic tissue damage induced by Helicobacter pylori (HP)-driven inflammation is considered the main risk of gastric carcinoma (GC). Epstein–Barr virus (EBV) infection has also been associated with GC. In this study, we aim to address the role of EBV in inflammatory GC precursor lesions and its added risk to HP infection.MethodsAntibodies against EBV, HP and the bacterial virulence factor CagA were measured in sera from 525 Mexican and Paraguayan patients with gastric disease. Gastric samples were characterised according to the updated Sydney classification and associations were estimated between antibody responses and severity of both tissue damage and inflammation.ResultsWe found significant associations (odd ratios and trends) between EBV and HP copositivity and premalignant lesions and intestinal-type GC. The EBV and HP coinfection was also significantly associated with increased infiltration of immune cells. No association was found between EBV and the less inflammation-driven diffuse-type GC.ConclusionsOur study suggests that EBV co-participates with HP to induce severe inflammation, increasing the risk of progression to intestinal-type GC.
| S-EPMC4580389 | biostudies-literature
Project description:A small set of gastric adenocarcinomas (9%) harbor Epstein-Barr virus (EBV) DNA within malignant cells, and the virus is not an innocent bystander but rather is intimately linked to pathogenesis and tumor maintenance. Evidence comes from unique genomic features of host DNA, mRNA, microRNA and CpG methylation profiles as revealed by recent comprehensive genomic analysis by The Cancer Genome Atlas Network. Their data show that gastric cancer is not one disease but rather comprises four major classes: EBV-positive, microsatellite instability (MSI), genomically stable and chromosome instability. The EBV-positive class has even more marked CpG methylation than does the MSI class, and viral cancers have a unique pattern of methylation linked to the downregulation of CDKN2A (p16) but not MLH1. EBV-positive cancers often have mutated PIK3CA and ARID1A and an amplified 9p24.1 locus linked to overexpression of JAK2, CD274 (PD-L1) and PDCD1LG2 (PD-L2). Multiple noncoding viral RNAs are highly expressed. Patients who fail standard therapy may qualify for enrollment in clinical trials targeting cancer-related human gene pathways or promoting destruction of infected cells through lytic induction of EBV genes. Genomic tests such as the GastroGenus Gastric Cancer Classifier are available to identify actionable variants in formalin-fixed cancer tissue of affected patients.
| S-EPMC4314585 | biostudies-literature
Project description:Epstein-Barr virus (EBV) and Helicobacter pylori (H. pylori) are two pathogens associated with the development of various human cancers. The coexistence of both microorganisms in gastric cancer specimens has been increasingly reported, suggesting that crosstalk of both pathogens may be implicated in the carcinogenesis process. Considering that chronic inflammation is an initial step in the development of several cancers, including gastric cancer, we conducted a systematic review to comprehensively evaluate publications in which EBV and H. pylori co-infection has been documented in patients with non-malignant gastroduodenal disorders (NMGDs), including gastritis, peptic ulcer disease (PUD), and dyspepsia. We searched the PubMed database up to August 2019, as well as publication references and, among the nine studies that met the inclusion criteria, we identified six studies assessing EBV infection directly in gastric tissues (total 949 patients) and three studies in which EBV infection status was determined by serological methods (total 662 patients). Due to the substantial methodological and clinical heterogeneity among studies identified, we could not conduct a meta-analysis. The overall prevalence of EBV + H. pylori co-infection in NMGDs was 34% (range 1.8% to 60%). A higher co-infection rate (EBV + H. pylori) was reported in studies in which EBV was documented by serological methods in comparison with studies in which EBV infection was directly assessed in gastric specimens. The majority of these studies were conducted in Latin-America and India, with most of them comparing NMGDs with gastric cancer, but there were no studies comparing the co-infection rate in NMGDs with that in asymptomatic individuals. In comparison with gastritis caused by only one of these pathogens, EBV + H. pylori co-infection was associated with increased severity of gastric inflammation. In conclusion, only relatively small studies testing EBV and H. pylori co-infection in NMGDs have been published to date and the variable report results are likely influenced by geographic factors and detection methods.
| S-EPMC7168260 | biostudies-literature
Project description:Gastric adenocarcinoma is the second leading cause of cancer death worldwide. Epstein-Barr virus (EBV) is present in the malignant cells of approximately 10% of cases. It is unclear whether EBV is being missed in some gastric adenocarcinomas due to insensitive test methods or partial EBV genome loss. In this study, we screened 113 gastric adenocarcinomas from low- and high-incidence regions (United States and Central America) for the presence of EBV using a battery quantitative real-time PCR (Q-PCR) assays targeting disparate segments of the EBV genome (BamH1W, EBNA1, LMP1, LMP2, BZLF1, EBER1) and histochemical stains targeting EBV-encoded RNA (EBER), the latent proteins LMP1 and LMP2, and the lytic proteins BMRF1 and BZLF1. EBV DNA was detected by Q-PCR in 48/75 United States cancers (64%) and in 38/38 Central American cancers (100%), which was a significant difference. EBER was localized to malignant epithelial cells in 8/48 (17%) United States and 3/38 (8%) Central American cancers. Viral loads were considerably higher for EBER-positive vs EBER-negative cancers (mean 162 986 vs 62 EBV DNA copies per 100,000 cells). A viral load of 2000 copies per 100,000 cells is recommended as the threshold distinguishing EBER-positive from EBER-negative tumors. One infected cancer selectively failed to amplify the LMP2 gene because of a point mutation, whereas another cancer had an atypical pattern of Q-PCR positivity suggesting deletion of large segments of the EBV genome. Three different viral latency profiles were observed in the cancers based on constant expression of EBER and focal or variable expression of LMP1 or LMP2, without lytic protein expression. We conclude that EBV DNA levels generally reflect EBER status, and a panel of at least two Q-PCR assays is recommended for sensitive identification of infected cancers.
| S-EPMC2612099 | biostudies-literature
Project description:Epstein-Barr virus (EBV) is a causative agent of a variety of lymphomas, nasopharyngeal carcinoma (NPC), and ∼9% of gastric carcinomas (GCs). An important question is whether particular EBV variants are more oncogenic than others, but conclusions are currently hampered by the lack of sequenced EBV genomes. Here, we contribute to this question by mining whole-genome sequences of 201 GCs to identify 13 EBV-positive GCs and by assembling 13 new EBV genome sequences, almost doubling the number of available GC-derived EBV genome sequences and providing the first non-Asian EBV genome sequences from GC. Whole-genome sequence comparisons of all EBV isolates sequenced to date (85 from tumors and 57 from healthy individuals) showed that most GC and NPC EBV isolates were closely related although American Caucasian GC samples were more distant, suggesting a geographical component. However, EBV GC isolates were found to contain some consistent changes in protein sequences regardless of geographical origin. In addition, transcriptome data available for eight of the EBV-positive GCs were analyzed to determine which EBV genes are expressed in GC. In addition to the expected latency proteins (EBNA1, LMP1, and LMP2A), specific subsets of lytic genes were consistently expressed that did not reflect a typical lytic or abortive lytic infection, suggesting a novel mechanism of EBV gene regulation in the context of GC. These results are consistent with a model in which a combination of specific latent and lytic EBV proteins promotes tumorigenesis.IMPORTANCE Epstein-Barr virus (EBV) is a widespread virus that causes cancer, including gastric carcinoma (GC), in a small subset of individuals. An important question is whether particular EBV variants are more cancer associated than others, but more EBV sequences are required to address this question. Here, we have generated 13 new EBV genome sequences from GC, almost doubling the number of EBV sequences from GC isolates and providing the first EBV sequences from non-Asian GC. We further identify sequence changes in some EBV proteins common to GC isolates. In addition, gene expression analysis of eight of the EBV-positive GCs showed consistent expression of both the expected latency proteins and a subset of lytic proteins that was not consistent with typical lytic or abortive lytic expression. These results suggest that novel mechanisms activate expression of some EBV lytic proteins and that their expression may contribute to oncogenesis.
| S-EPMC5752941 | biostudies-literature
Project description:BackgroundThe controversy of CpG island methylator phenotype (CIMP) in gastric cancer persists, despite the fact that many studies have been conducted on its relation with helicobacter pylori (H. pylori), Epstein-Barr virus (EBV), and microsatellite instability (MSI) and prognosis. To drive a more precise estimate of this postulated relationship, a meta-analysis was performed based on existing relevant studies.MethodsWe combined individual patient data from 12 studies which involved 1000 patients with gastric cancer, which met the criteria. We tabulated and analyzed parameters from each study, including H. pylori, EBV, MSI, and clinical information of patients.ResultsThe overall OR for H. pylori infection in CIMP positive group vs. negative group revealed that significantly elevated risks of positive H. pylori infection in the former were achieved (OR 2.23 95% CI, 1.25-4.00; P = 0.007, Pheterogeneity = 0.05). Similarly, strong relation between EBV infection and CIMP was achieved by OR 51.27 (95% CI, 9.39-279.86; P<0.00001, Pheterogeneity = 0.39). The overall OR for MSI in CIMP positive group vs. negative group was 4.44 (95% CI, 1.17-16.88; P = 0.03, Pheterogeneity = 0.01). However, there did not appear to be any correlations with clinical parameters such as tumor site, pathological type, cell differentiation, TNM stage, distant metastasis, lymph node metastasis, and 5-year survival.ConclusionsThe meta-analysis highlights the strong relation of CIMP with H. pylori, EBV, and MSI, but CIMP can not be used as a prognostic marker for gastric cancer.
| S-EPMC3903497 | biostudies-literature
Project description:BackgroundH. pylori infection is acquired during childhood and causes a chronic inflammatory response in the gastric mucosa, which is considered the main risk factor to acquire gastric cancer (GC) later in life. More recently, infection by Epstein-Barr virus (EBV) have also been associated with GC. The role of EBV in early inflammatory responses and its relationship with H. pylori infection remains poorly studied. Here, we assessed whether EBV infection in children correlated with the stage of gastritis and whether co-infection with H. pylori affected the severity of inflammation.Methodology/principal findings333 pediatric patients with chronic abdominal pain were studied. From them, gastric biopsies were taken and inflammation graded according to the Sydney system; peripheral blood was drawn and antibodies against EBV (IgG and IgM anti-VCA) and H. pylori (IgG anti-whole bacteria and anti-CagA) were measured in sera. We found that children infected only by EBV presented mild mononuclear (MN) and none polymorphonuclear (PMN) cell infiltration, while those infected by H. pylori presented moderate MN and mild PMN. In contrast, patients co-infected with both pathogens were significantly associated with severe gastritis. Importantly, co-infection of H. pylori CagA+/EBV+ had a stronger association with severe MN (PR 3.0) and PMN (PR 7.2) cells than cases with single H. pylori CagA+ infection.Conclusions/significanceCo-infection with EBV and H. pylori in pediatric patients is associated with severe gastritis. Even single infections with H. pylori CagA+ strains are associated with mild to moderate infiltration arguing for a cooperative effect of H. pylori and EBV in the gastric mucosa and revealing a critical role for EBV previously un-appreciated. This study points out the need to study both pathogens to understand the mechanism behind severe damage of the gastric mucosa, which could identified children with increased risk to present more serious lesions later in life.
| S-EPMC3634751 | biostudies-literature