Implications of Helicobacter pylori infection for stomach cancer prevention

Accumulating evidence has implicated Helicobacter pylori, an established cause of chronic gastritis and peptic ulcer, in the etiology of gastric cancer. Control of this infection would reduce the occurrence of chronic gastritis and peptic ulcer and might substantially lower the risk of stomach cancer as well. The public health impact of this infectious agent warrants efforts to identify preventive measures. This paper reviews the evidence linking H. pylori infection to gastric cancer and evaluates the potential for control in high-risk populations. Current obstacles to H. pylori control are discussed, including the link to poor socioeconomic conditions, difficulty in identifying incident cases, lack of natural immunity to reinfection, limited effectiveness of antibiotic therapy in high-prevalence populations, and incomplete knowledge regarding the reservoir of infection, mode of transmission, host susceptibility factors, and the potential for developing an effective vaccine. Worthwhile avenues of research include studies designed to identify modifiable risk factors for acquisition of the infection, modifiable host factors that may increase resistance to chronic infection, more effective antibiotic therapies, and effective vaccines.

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Helicobacter pyloriAnti-CagA Antibodies: Prevalence in Symptomatic and Asymptomatic Subjects in Turkey

Canadian Journal of Gastroenterology ◽

10.1155/2002/589087 ◽

2002 ◽

Vol 16 (8) ◽

pp. 527-532 ◽

Cited By ~ 13

Author(s):

M Fatih Abasiyanik ◽

Ersan Sander ◽

Barik A Salih

Keyword(s):

Gastric Cancer ◽

Duodenal Ulcer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Chronic Gastritis ◽

Molecular Weights ◽

Cancer Antigens ◽

Gastroduodenal Disease ◽

H Pylori ◽

Asymptomatic Subjects

BACKGROUND: Several reports have shown the prevalence of anti-CagA antibodies to be associated with the development of peptic ulcer diseases, while others have indicated that there is no such association.AIM: To examine the prevalence of antibodies to CagA and otherHelicobacter pyloriantigens in symptomatic and asymptomatic subjects in Turkey.SUBJECTS AND METHODS: Sixty-six symptomatic subjects, 16 to 74 years of age, were examined forH pyloriby biopsy-based tests and ELISA. One hundred nineteen asymptomatic subjects, 20 to 65 years of age, were also tested serologically for the presence ofH pylori. Samples from both groups that were found to be positive forH pyloriby ELISA were then tested by immunoblotting.RESULTS: Fifty-four (82%) symptomatic subjects and 76 (64%) asymptomatic subjects were found to beH pylori-positive by ELISA. Samples from 30 symptomatic subjects who were found to beH pylori-positive by ELISA were analyzed by immunoblotting. Antibodies to CagA (116 kDa) antigen were detected in immunoblots of 11 of 14 (79%) with chronic gastritis, 12 of 13 (92%) with duodenal ulcer and three of three (100%) with gastric cancer. Antigens of the following molecular weights were also detected in these 30 subjects: 89 kDa (VacA) in 21 (70%), 37 kDa in 21 (70%), 35 kDa in 19 (63%), 30 kDa in 27 (90%) and 19.5 kDa in 19 (63%). Immunoblots of 40 ELISA-positive asymptomatic subjects showed that 33 (83%) had antibodies to CagA antigen, 26 (65%) to VacA antigen, 30 (75%) to a 37 kDa antigen, 30 (75%) to a 35 kDa antigen, 39 (98%) to a 30 kDa antigen and 36 (90%) to a 19.5 kDa antigen.CONCLUSIONS: Antibodies to CagA antigen were prevalent in both groups, regardless of the presence of gastroduodenal disease.

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Induction and prevention of gastric cancer with combined Helicobacter pylori and capsaicin administration and DFMO treatment, respectively

10.21203/rs.2.21633/v1 ◽

2020 ◽

Author(s):

Faisal Aziz ◽

Mingxia Xin ◽

Yunfeng Gao ◽

Josh Monts ◽

Kjersten Monson ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Mouse Models ◽

Chronic Gastritis ◽

Molecular Mechanisms ◽

Gastric Carcinogenesis ◽

Lifestyle Changes ◽

Host Susceptibility ◽

Anti Inflammatory ◽

H Pylori

Abstract Background: Gastric cancer risk evolves over time due to environmental, dietary, and lifestyle changes including Helicobacter pylori (H. pylori) infection and consumption of hot peppers (i.e. capsaicin). H. pylori infection promotes gastric mucosal injury in the early phase of capsaicin exposure. In addition, capsaicin consumption is reported to suppress immune function and increase host susceptibility to microbial infection. This relationship suggests a need to investigate the mechanism of how both H. pylori infection and capsaicin contribute to gastric inflammation and lead to gastric cancer. No previous experimental animal models have been developed to study this dual association. Here we developed a series of mouse models that progress from chronic gastritis to gastric cancer. C57-Balb/c mice were infected with the H. pylori (SS1) strain and then fed capsaicin (0.05% or 0.2g/kg/day) or not. Consequently, we investigated the association between H. pylori infection and capsaicin consumption during the initiation of gastric inflammation and the later development of gastric cancer. Tumor size and phenotype were analyzed to determine the molecular mechanism driving the shift from gastritis to stomach cancer. Gastric carcinogenesis was also prevented in these models using the ornithine decarboxylase inhibitor DFMO (2-difluoromethylornithine). Results: This study provides evidence showing that a combination of H. pylori infection and capsaicin consumption leads to gastric carcinogenesis. The transition from chronic gastritis to gastric cancer is mediated through interleukin-6 (IL-6) stimulation with an incidence rate of 50%. However, this progression can be prevented by treating with anti-inflammatory agents. In particular, we used DFMO to prevent gastric tumorigenesis by reducing inflammation and promoting recovery of disease-free stasis. The anti-inflammatory role of DFMO highlights the injurious effect of inflammation in gastric cancer development and the need to reduce gastric inflammation for cancer prevention. Conclusions: Overall, these mouse models provide reliable systems for analyzing the molecular mechanisms and synergistic effects of H. pylori and capsaicin on human cancer etiology. Accordingly, preventive measures like reduced capsaicin consumption, H. pylori clearance, and DFMO treatment can lessen gastric cancer incidence. Lastly, anti-inflammatory agents like DFMO can play important roles in prevention of inflammation-associated gastric cancer.

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Determination of Helicobacter pyloriVirulence by Simple Gene Analysis of the cagPathogenicity Island

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.8.1.181-186.2001 ◽

2001 ◽

Vol 8 (1) ◽

pp. 181-186 ◽

Cited By ~ 59

Author(s):

Tsuneo Ikenoue ◽

Shin Maeda ◽

Keiji Ogura ◽

Masao Akanuma ◽

Yuzo Mitsuno ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Chronic Gastritis ◽

Promoter Region ◽

Neutrophil Infiltration ◽

Japanese Patients ◽

Nucleic Acid Amplification ◽

H Pylori

ABSTRACT Nucleic acid amplification was performed for five loci in thecag pathogenicity island (PAI) of Helicobacter pylori (comprising cagA, the cagApromoter region, cagE, cagT, and the left end of cagII [LEC]), and gastric inflammation in patients was evaluated. Of 204 H. pylori isolates from Japanese patients (53 with peptic ulcer, 55 with gastric cancer, and 96 with chronic gastritis), 197 (96.6%) were positive for all five loci. Two isolates (1%) were negative for all five loci, and five isolates (2.4%) were positive for only cagA and LEC. These latter seven isolates were all from patients with mild chronic gastritis. Neutrophil infiltration in gastric mucosa was significantly milder in patients infected with partially or totally deleted-PAI strains than in those with intact-PAI strains. The cagE gene was a more accurate marker of an intact cag PAI than thecagA gene, and cagE seemed to be more useful in discriminating between H. pylori strains causing different rates of disease progression.

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Virulence genes of Helicobacter pylori in the Dominican Republic

Journal of Medical Microbiology ◽

10.1099/jmm.0.075275-0 ◽

2014 ◽

Vol 63 (9) ◽

pp. 1189-1196 ◽

Cited By ~ 18

Author(s):

Seiji Shiota ◽

Modesto Cruz ◽

José A. Jiménez Abreu ◽

Takahiro Mitsui ◽

Hideo Terao ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Dominican Republic ◽

Infection Rate ◽

Rapid Urease Test ◽

Test Culture ◽

Urease Test ◽

The Status ◽

H Pylori

Although the incidence of gastric cancer in the Dominican Republic is not high, the disease remains a significant health problem. We first conducted a detailed analysis of Helicobacter pylori status in the Dominican Republic. In total, 158 patients (103 females and 55 males; mean age 47.1±16.2 years) were recruited. The status of H. pylori infection was determined based on four tests: rapid urease test, culture test, histological test and immunohistochemistry. The status of cagA and vacA genotypes in H. pylori was examined using PCR and gene sequencing. The overall prevalence of H. pylori infection was 58.9 %. No relationship was found between the H. pylori infection rate and the age range of 17–91 years. Even in the youngest group (patients aged <29 years), the H. pylori infection rate was 62.5 %. Peptic ulcer was found in 23 patients and gastric cancer was found in one patient. The H. pylori infection rate in patients with peptic ulcer was significantly higher than that in patients with gastritis (82.6 versus 54.5 %, P<0.01). The cagA-positive/vacA s1m1 genotype was the most prevalent (43/64, 67.2 %). Compared with H. pylori-negative patients, H. pylori-positive patients showed more severe gastritis. Furthermore, the presence of cagA was related to the presence of more severe gastritis. All CagA-positive strains had Western-type CagA. In conclusion, we found that H. pylori infection is a risk factor for peptic ulcer in the Dominican Republic. Patients with cagA-positive H. pylori could be at higher risk for severe inflammation and atrophy.

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Helicobacter Pylori Associated Antral Gastritis in Peptic Ulcer Disease Patients and Normal Healthy Population of Kashmir, India

Diagnostic and Therapeutic Endoscopy ◽

10.1155/dte.4.135 ◽

1998 ◽

Vol 4 (3) ◽

pp. 135-139 ◽

Cited By ~ 2

Author(s):

Gh. Jeelani Romshoo ◽

G. M. Malik ◽

M. Youssuf Bhat ◽

Ab. Rashid rather ◽

Javaid Ahmad Basu ◽

...

Keyword(s):

Helicobacter Pylori ◽

Peptic Ulcer ◽

Gastric Ulcer ◽

Peptic Ulcer Disease ◽

Healthy Volunteers ◽

Chronic Gastritis ◽

Healthy Population ◽

Ulcer Disease ◽

Antral Gastritis ◽

H Pylori

Aim: To study the association of Helicobacter pylori infection with chronic antral gastritis in peptic ulcer disease patients and healthy population of Kashmir.Methods: 50 peptic ulcer patients (duodenal ulcer = 46, gastric ulcer = 2 and combined duodenal and gastric ulcer = 2) and 30 asymptomatic healthy volunteers were included in this study. Peptic ulcer was diagnosed on endoscopic examination. 4–6 punch biopsies were taken from gastric antrum in all the individuals and in case of gastric ulcer an additional biopsy was taken from the edge of the ulcer to exclude its malignant nature. Helicobacter pylori (H. pylori) organism was diagnosed using three different test methods, viz. Histology (using Giemsa Stain), Microbiology (Gram Stain) and Biochemistry (using one minute Endoscopy Room Test). Histological diagnosis of H. pylori was taken as the “gold standard” for the presence of H. pylori organism. Histological diagnosis of gastritis was made using Hematoxylin and Eosin Stain and the gastritis was classified as active chronic gastritis and superficial chronic gastritis.Results: Out of 30 peptic ulcer disease patients with associated antral gastritis, 27 (90%) were positive for H. pylori on histological examination (13 superficial chronic gastritis and 14 active chronic gastritis) whereas out of 8 healthy volunteers with histological evidence of chronic antral gastritis, H. pylori was observed in 7 individuals (87.50%) (4 active chronic gastritis and 3 superficial chronic gastritis).Conclusion: A highly significant association between H. pylori infection with chronic antral gastritis both in peptic ulcer disease patients and healthy volunteers of Kashmir was found in this study. Association between H. pylori infection and chronic gastritis was 90% in peptic ulcer group and 87.50% in healthy population (P<0.005).

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Association of Helicobacter pylori infection and stomach cancer: our experience

International Surgery Journal ◽

10.18203/2349-2902.isj20183193 ◽

2018 ◽

Vol 5 (8) ◽

pp. 2794

Author(s):

N. G. Javan ◽

Wormi Sharon

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Carcinoma ◽

Stomach Cancer ◽

Histopathological Examination ◽

Chronic Atrophic Gastritis ◽

Helicobacter Pylori Infection ◽

Future Research ◽

Gastric Cancer Prevention ◽

H Pylori

Background: Infection with Helicobacter pylori (H. pylori) has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. There are data on the epidemiology, pathophysiology, and histology of this disease that show that Helicobacter pylori gastritis has an important role in gastric carcinogenesis. However, it has to be considered that only very few of those infected with Helicobacter pylori will develop gastric cancer. Hence, it will be a major target of future research to identify individuals who carry a greater risk for developing gastric cancer, and therefore may benefit from eradication of Helicobacter pylori in terms of gastric cancer prevention. Various studies revealed that approximately more than 50% of the world’s human population is infected by Helicobacter pylori. In underdeveloped countries, this association is shown to be much higher according to different studies.Methods: This study was conducted over a period of 36 months from 1st January 2014 till December 31st, 2016. All patients who underwent Gastrectomy during this period were taken. All specimens were investigated to see presence of helicobacter pylori by histological examination. A total of 50 Gastrectomy was performed by one surgical team over 36-month period.Results: Out of 50 patients, Helicobacter pylori positivity was seen in 33 (66%) cases by histopathological examination (HPE). Gastric cancer is more prevalent among males 31 (62%) as compared to 19 (38%) in females. It is more common among the older age group.Conclusions: Helicobacter pylori infection is higher in prevalence in cases of stomach cancer. Present study also showed that there is significant association of Helicobacter pylori infection with gastric carcinoma. Helicobacter pylori infection could be one of the etiological factors for gastric carcinoma.

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Risk assessment of gastric cancer in the presence of Helicobacter pylori cagA and hopQII genes

Cellular and Molecular Biology ◽

10.14715/cmb/2021.67.4.33 ◽

2022 ◽

Vol 67 (4) ◽

pp. 299-305

Author(s):

Xiaohui Guo ◽

Binghua Yin ◽

Can Wang ◽

Huazhi Huo ◽

Zahra Aziziaram

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Patients ◽

Stomach Cancer ◽

Bacterial Infections ◽

Healthy People ◽

Healthy Individuals ◽

Duodenal Ulcers ◽

Pathogenic Genes ◽

H Pylori

Helicobacter pylori bacterium is one of the most common bacterial infections globally and is the leading cause of indigestion, gastric and duodenal ulcers, and gastric cancer. This bacterium can escape the antibacterial effects of stomach acid by adapting to the inner layers of the stomach. It combines with the natural sugars in the gastric mucosa. The compound is so effective that it makes bacterium resistant. For genes related to the pathogenesis of H. pylori, using the existence of genes such as cagA, hopQI, and hopQII, PCR is performed on some of these genes to amplify fragments of different lengths. One of the less-studied cases is that two or more pathogenic genes are simultaneously associated with H. pylori. This study examined the frequency of diseases and healthy individuals infected with H. pylori and cagA and hopQII genotypes. To diagnose H. pylori infection in healthy and stomach cancer patients, the PCR products are electrophoresed on the agarose gel after glmM gene amplification by PCR. To this aim, stomach tissue biopsies were used for patients, and saliva was used for healthy individuals. For this purpose, 150 gastric biopsy samples from stomach cancer patients and 150 saliva samples from healthy people were collected. Data showed a significant relationship between the coexistence of two genes, cagA and hopQII, and stomach cancer. 34.2% of patients and 10.1% of healthy individuals showed two genotypes, while other healthy people (89.9%) infected with H. pylori did not have this genotype. Therefore, the simultaneous presence of these two bacterial genes in human societies can be an essential biomarker for the diagnosis and prognosis of gastric cancer.

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Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

Infection and Immunity ◽

10.1128/iai.72.2.1043-1056.2004 ◽

2004 ◽

Vol 72 (2) ◽

pp. 1043-1056 ◽

Cited By ~ 87

Author(s):

Steffen Backert ◽

Tobias Schwarz ◽

Stephan Miehlke ◽

Christian Kirsch ◽

Christian Sommer ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Pathogenicity Island ◽

Epidemiological Studies ◽

Disease Development ◽

Gastric Diseases ◽

H Pylori ◽

Gastric Cancer Patients

ABSTRACT Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.

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Precancerous Gastric Lesions with Helicobacter pylori vacA+/babA2+/oipA+ Genotype Increase the Risk of Gastric Cancer

BioMed Research International ◽

10.1155/2020/7243029 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Theeraya Simawaranon Bartpho ◽

Wareeporn Wattanawongdon ◽

Taweesak Tongtawee ◽

Chatchanok Paoin ◽

Kokiet Kangwantas ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Clinical Outcomes ◽

Chronic Gastritis ◽

Virulence Genes ◽

Gastric Lesions ◽

Precancerous Gastric Lesions ◽

Increased Risk ◽

H Pylori ◽

Gastric Cancer Patients

Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real-time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.024, and OR = 2.79; 95% CI = 1.58–5.41; P=0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P=0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.

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Recent Advances inHelicobacter pyloriInfection in Children: From the Petri Dish to the Playgound

Canadian Journal of Gastroenterology ◽

10.1155/2003/809530 ◽

2003 ◽

Vol 17 (7) ◽

pp. 448-454 ◽

Cited By ~ 4

Author(s):

Peng-Yuan Zheng ◽

Nicola L Jones

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Petri Dish ◽

Host Factors ◽

Causative Role ◽

Ulcer Disease ◽

Recent Advances ◽

H Pylori ◽

Development Of Gastric Cancer

Helicobacter pyloriinfection is acquired in childhood, plays a causative role in chronic gastritis and peptic ulcer disease, and is associated with the development of gastric cancer. The present review focuses on recent advances in the scientific knowledge ofH pyloriinfection in children, including clinical sequelae, diagnosis and treatment. In addition, recent insights regarding both bacterial and host factors that mediate human diseases associated withH pyloriinfection are discussed.

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