scholarly journals New Biology to New Treatment of Helicobacter pylori-Induced Gastric Cancer

2016 ◽  
Vol 34 (5) ◽  
pp. 510-516 ◽  
Author(s):  
Richard M. Peek Jr.
Keyword(s):  
Gastric Cancer ◽  
Salt Intake ◽  
Disease Risk ◽  
Host Cells ◽  
Human Populations ◽  
High Salt Intake ◽  
Increased Risk ◽  
New Biology ◽  
New Treatment ◽  
H Pylori

Background:Helicobacter pylori is a bacterial carcinogen that is supposed to have the highest known level of risk for the development of gastric cancer, a disease that claims hundreds of thousands of lives per year. Approximately 89% of the global gastric cancer burden and 5.5% of malignancies worldwide are attributed to H. pylori-induced inflammation and injury. However, only a fraction of colonized persons ever develop neoplasia, and disease risk involves well-choreographed interactions between pathogen and host, which are dependent upon strain-specific bacterial factors, host genotypic traits, and/or environmental conditions. Key Messages: One H. pylori strain-specific virulence determinant that augments the risk for gastric cancer is the cag pathogenicity island, a secretion system that injects the bacterial oncoprotein CagA into host cells. Host polymorphisms within genes that regulate immunity and oncogenesis also heighten the risk for gastric cancer, in conjunction with H. pylori strain-specific constituents. Further, conditions such as iron deficiency and high salt intake can influence H. pylori phenotypes that lower the threshold for disease. Conclusions: Delineation of bacterial, host, and environmental mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer, but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.

scholarly journals Association between Dietary Salt Intake and Progression in the Gastric Precancerous Process

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 467 ◽  
Author(s):  
Susan Thapa ◽  
Lori A. Fischbach ◽  
Robert Delongchamp ◽  
Mohammed F. Faramawi ◽  
Mohammed Orloff
Keyword(s):  
Gastric Cancer ◽  
Confidence Interval ◽  
Risk Ratio ◽  
Salt Intake ◽  
Precancerous Lesions ◽  
Urinary Sodium ◽  
Adjusted Risk ◽  
Adjusted Risk Ratio ◽  
Increased Risk ◽  
H Pylori

Gastric cancer is the third leading cause of cancer mortality worldwide. Studies investigating the effect of salt on gastric cancer have mainly used self-reported measures, which are not as accurate as sodium/creatinine ratios because individuals may not know the amount of salt in their food. Using data from a prospective cohort study, we investigated the effect of salt intake on progression to gastric precancerous lesions. Salt intake was estimated by urinary sodium/creatinine ratios, self-reported frequencies of adding salt to food, and total added table salt. We repeated the analyses among groups with and without Helicobacter pylori infection. We did not observe a positive association between salt intake, measured by urinary sodium/creatinine ratio, and overall progression in the gastric precancerous process (adjusted risk ratio (RR): 0.94; 95% confidence interval (CI) 0.76–1.15). We did observe an association between salt intake and increased risk for progression to dysplasia or gastric cancer overall (adjusted risk ratio (RR): 1.32; 95% confidence interval (CI): 0.96–1.81), especially among those who continued to have H. pylori infection at the five-month follow-up (adjusted RR: 1.53; 95% CI: 1.12–2.09), and among those who had persistent H. pylori infection over 12 years (adjusted RR: 1.49; 95% CI: 1.09–2.05). Salt intake may increase the risk of gastric dysplasia or gastric cancer in individuals with H. pylori infection.

scholarly journals The gastric cancer

2013 ◽  
pp. 192-201 ◽  
Author(s):  
Pelayo Correa ◽  
María Blanca Piazuelo
Keyword(s):  
Gastric Cancer ◽  
Salt Intake ◽  
Early Stage ◽  
Treatment Options ◽  
The Body ◽  
Effective Measure ◽  
High Salt Intake ◽  
Risk Patients ◽  
Advanced Stages ◽  
H Pylori

Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidencein some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases beingdiagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is acomplex and multi-factored process involving a number of etiological factors and multiple genetic and epigenetic alterations.Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and, in a small percentage ofpatients, a family genetic component. More than 90% of stomach cancers are adenocarcinomas, which are classified intotwo major histological groups: intestinal and diffuse. Intestinal adenocarcinoma is preceded by a sequence of gastric lesionsknown as Correa´s cascade. According to the anatomical position, adenocarcinomas are classified as proximal (originatingin the cardia) and distal (originating in the body and antrum). This is a classification that recognizes two different clinicalentities. In general, the only possible cure for the disease is resection of the tumor in an early stage for which the identificationand monitoring of at-risk patients play a significant role. With the exception of Japan, no effective early detection programsexist. Anti-H. pylori has been shown to be an effective measure in the prevention of gastric cancer.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

2019 ◽  
Author(s):  
Wongwarut Boonyanugomol ◽  
Kamolchanok Rukseree ◽  
Worrarat Kongkasame ◽  
Prasit Palittapongarnpim ◽  
Seung-Chul Baik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Gene Polymorphisms ◽  
Inflammatory Responses ◽  
Increased Risk ◽  
Cxc Chemokine ◽  
H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.  

scholarly journals Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity

2021 ◽  
Vol 9 ◽  
Author(s):  
Stella G. Hoft ◽  
Christine N. Noto ◽  
Richard J. DiPaolo
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Gastric Adenocarcinoma ◽  
Inflammatory Diseases ◽  
The United States ◽  
Autoimmune Gastritis ◽  
Gastric Disease ◽  
Increased Risk ◽  
H Pylori ◽  
Gastrointestinal Ulceration

Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises >90% of gastric cancers, is multifactorial, but most associated with Helicobacter pylori infection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+ T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clear H. pylori infection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection with H. pylori initiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, and H. pylori infection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.

scholarly journals Role of Bacterial Overgrowth in the Stomach as an Additional Risk Factor for Gastritis

2003 ◽  
Vol 17 (suppl b) ◽  
pp. 13B-17B ◽  
Author(s):  
Gregory Naylor ◽  
Anthony Axon
Keyword(s):  
Gastric Cancer ◽  
Cell Mass ◽  
Bacterial Overgrowth ◽  
Nitroso Compounds ◽  
Current Evidence ◽  
Additional Risk Factor ◽  
Proximal Small Bowel ◽  
Increased Risk ◽  
H Pylori

Gastric bacteria can either be ingested or ascend from the distal bowel; however, their survival is usually limited by gastric acidity and motility. A reduction in gastric acid can result in bacterial overgrowth in the stomach and proximal small bowel, and the number of organisms rises as the intragastric pH rises.The increased risk of noncardia gastric cancer seen in patients with hypochlorhydria may be explained by an excess of nitrites and N-nitroso compounds (NOCs). These compounds are found in the diet of populations with a high gastric cancer risk, but can also be produced by the organisms that exist in the hypochlorhydria stomach. It has long been hypothsized that nitrites and NOCs act as one of the triggers in the atrophy-metaplasia-dysplasia-carcinoma path. However, although indirect data have linked the premalignant changes of metaplasia and dysplasia to NOCs, direct measurement of gastric nitrites and NOCs has not confirmed such a link.The role ofHelicobacter pyloriin bacterial overgrowth is mainly as a cause of hypochlorhydria resulting from atrophic gastritis, leading to a reduction in the parietal cell mass.Acid-suppressing drugs can result in bacterial overgrowth and increased nitrites and NOCs, although there is no current evidence for an increased risk of gastric cancer in patients taking them. One explanation is that the stomach appears to be colonized by different organisms than those in patients with hypochlorhydria for other reasons. There is some evidence that bacterial overgrowth per se can cause gastric inflammation in mice; however, although in humans the degree of gastric inflammation is greater when overgrowth is more prominant this may simply reflect the greater degree of hypochlorhydria in patients with a more severe H pylori-induced inflammation.

Age-dependent prevalence of H. pylori associated gastritis phenotypes with increased risk for gastric cancer

2003 ◽  
Vol 124 (4) ◽  
pp. A648-A649 ◽  
Author(s):  
Andreas Leodolter ◽  
Matthias Ebert ◽  
Stefan Kahl ◽  
Michael Vieth ◽  
Peter Malfertheiner
Keyword(s):  
Gastric Cancer ◽  
Increased Risk ◽  
Age Dependent ◽  
H Pylori

scholarly journals Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence

2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Randomized Clinical Trials ◽  
Bacterial Overgrowth ◽  
Current Evidence ◽  
Neoplastic Progression ◽  
Increased Risk ◽  
H Pylori

Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual’s risk–benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.

scholarly journals High Salt Intake and Risk of Chronic Bronchitis: The Copenhagen Male Study—A 10-Year Followup

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Poul Suadicani ◽  
Hans Ole Hein ◽  
Finn Gyntelberg
Keyword(s):  
Risk Factor ◽  
Chronic Bronchitis ◽  
Salt Intake ◽  
Multiple Logistic Regression Analysis ◽  
Bronchial Hyperresponsiveness ◽  
High Salt ◽  
Dust Exposure ◽  
High Salt Intake ◽  
Increased Risk ◽  
Occupational Dust Exposure

Objective. The role of salt intake as a risk factor for asthma, bronchial hyperresponsiveness, and other bronchial symptoms has been addressed in a number of studies. Collectively, these studies indicate an increased risk of bronchial symptoms with high consumption of salt, but the issue remains controversial. We tested prospectively the hypothesis that salt intake would be an independent risk factor for chronic bronchitis (CB). Design. A 10-year prospective study of 2,183 men aged 46 to 65 years without any relevant lung symptoms at baseline. Main Outcome. Chronic bronchitis. Results. During the 10-year followup, the overall incidence of CB was 7.1% among men without any relevant lung symptoms at baseline. In a multiple logistic regression analysis, controlling for age, smoking habits, occupational dust exposure, alcohol use, and social class, the odds ratio associated with self-assessed high salt preference (reported by 24%) was 1.6 (1.1–2.4). Interpretation. The results suggest that salt restriction may prevent chronic bronchitis.

Sign in / Sign up

Export Citation Format

Share Document