Chronic gastritis and carcinogenesis issues

Risk factors contributing to the transformation of chronic atrophic gastritis into gastric cancer are analyzed. Detection and monitoring of patients with precancerous conditions/lesions (precancerous changes), proper screening of H. pylori make early diagnosis of gastric cancer real. Features of precancerous conditions are given in order of increasing risk of developing gastric cancer. Adenomatous polyps of the stomach take the first place. Subsequent precancerous conditions include: cancer of the operated stomach, Menetria disease (hypertrophic gastropathy), B12-deficient anemia, and gastric ulcer. A definition of intestinal metaplasia subtypes is proposed as a risk factor for gastric cancer, dividing into complete and incomplete one, taking into account reduction in the expression of gastric mucins MUC1, MUC5AC and MUC6. Currently, the development of gastric cancer (mainly of the “intestinal type”) is considered as a multistage process involving the sequence of mucosal change, such as chronic inflammation, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma. Role of the organism’s genetic susceptibility to H. pylori infection, factors of pathogenicity contributing to epithelial metaplasia, are analyzed. Role of Toll-like type 4 receptors (TLR4) involved in the recognition of H. pylori is clarified. It is with this type of receptors that the development of an excessive immune response of the host is associated, resulting in damage to the mucous membrane in H. pylori-infected individuals. In particular, carriers of TLR4+896A> G polymorphism have a more severe atrophy of the stomach and degree of inflammation, as well as an increased risk of non-cardiac gastric cancer.

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

Canadian Journal of Gastroenterology ◽

10.1155/2003/350347 ◽

2003 ◽

Vol 17 (suppl b) ◽

pp. 13B-17B ◽

Cited By ~ 15

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.

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The evolving role of endoscopy in the diagnosis of premalignant gastric lesions

F1000Research ◽

10.12688/f1000research.12087.1 ◽

2018 ◽

Vol 7 ◽

pp. 715 ◽

Cited By ~ 5

Author(s):

William Waddingham ◽

David Graham ◽

Matthew Banks ◽

Marnix Jansen

Keyword(s):

Risk Assessment ◽

Intestinal Metaplasia ◽

Narrow Band Imaging ◽

Sampling Error ◽

Evolutionary Model ◽

Chronic Atrophic Gastritis ◽

Recent Advances ◽

Increased Risk ◽

High Degree

Gastric adenocarcinoma is a disease that is often detected late, at a stage when curative treatment is unachievable. This must be addressed through changes in our approach to the identification of patients at increased risk by improving the detection and risk assessment of premalignant changes in the stomach, including chronic atrophic gastritis and intestinal metaplasia. Current guidelines recommend utilising random biopsies in a pathology-led approach in order to stage the extent and severity of gastritis and intestinal metaplasia. This random method is poorly reproducible and prone to sampling error and fails to acknowledge recent advances in our understanding of the progression to gastric cancer as a non-linear, branching evolutionary model. Data suggest that recent advances in endoscopic imaging modalities, such as narrow band imaging, can achieve a high degree of accuracy in the stomach for the diagnosis of these premalignant changes. In this review, we outline recent data to support a paradigm shift towards an endoscopy-led approach to diagnosis and staging of premalignant changes in the stomach. High-quality endoscopic interrogation of the chronically inflamed stomach mucosa, supported by targeted biopsies, will lead to more accurate risk assessment, with reduced rates of under or missed diagnoses.

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Trefoil Factor Family in Pre-neoplastic Lesions and Gastric Cancer

The Cancer Press ◽

10.15562/tcp.70 ◽

2018 ◽

Vol 4 ◽

Author(s):

Zahra Behrooznia ◽

Pouya Ghaderi ◽

Narges Jafarzadeh ◽

Azra Izanloo ◽

Sepideh Mansoori Majoofardi ◽

...

Keyword(s):

Gastric Cancer ◽

Gastrointestinal Tract ◽

Atrophic Gastritis ◽

Intestinal Metaplasia ◽

Chronic Atrophic Gastritis ◽

Suppressor Activity ◽

Neoplastic Lesions ◽

Tumor Suppressor Activity ◽

Trefoil Factor Family

Gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide. Although the global incidence of gastric cancer has been decreased dramatically in recent decades, north and northwest of Iran have the highest incidence rate of gastric cancer. Whilst the surgical procedures for gastric cancer have been improved, there is no cure for that. The intestinal type of GC results from pre-neoplastic conditions including atrophic gastritis, intestinal metaplasia and dysplasia. Trefoil Factors Family proteins (TFFs) are small and stable molecules secreted by the mammalian gastrointestinal tract. TFFs constitute a family of three peptides (TFF1, TFF2and TFF3) that are widely expressed in a tissue specific manner in the gastrointestinal tract. Variable TFFs expression in gastric cancer and pre-neoplastic lesions has been found. TFF1 has a tumor suppressor activity and inhibits tumorogenesis in gastric cancer. Its expression decreases in gastritis, gastric atrophy, dysplasia, intestinal metaplasia and gastric cancer.TFF2 has a protective effect on gastrointestinal epithelium. As a prognostic factor, TFF2 expression decreases in gastric ulcer, chronic atrophic gastritis and gastric cancer. TFF3 is considered as an oncogenic factor in gastric tissues. Whilst the normal gastric tissues don’t express TFF3, it increases in intestinal metaplasia. Therefore, more studies are necessary to clarify the role of TFFs in GC and pre-neoplastic conditions. This review has focused on elucidating the important role of TFFs in gastric cancer and pre-neoplastic lesions.

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Combined Gastric and Colorectal Cancer Screening—A New Strategy

International Journal of Molecular Sciences ◽

10.3390/ijms19123854 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3854 ◽

Cited By ~ 2

Author(s):

Michael Selgrad ◽

Jan Bornschein ◽

Arne Kandulski ◽

Jochen Weigt ◽

Albert Roessner ◽

...

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Intestinal Metaplasia ◽

Incidence Rates ◽

Screening Colonoscopy ◽

Serum Pepsinogen ◽

Serum Samples ◽

Serological Screening ◽

Increased Risk ◽

H Pylori

Background: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. Methods: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). Results: H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III–IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = −0.425; p < 0.001) and OLGIM (r = −0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29–23.54; p < 0.001) for gastric preneoplastic changes. Conclusions: The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population.

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Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls

Journal of Medical Microbiology ◽

10.1099/jmm.0.007302-0 ◽

2009 ◽

Vol 58 (4) ◽

pp. 509-516 ◽

Cited By ~ 156

Author(s):

Johan Dicksved ◽

Mathilda Lindberg ◽

Magnus Rosenquist ◽

Helena Enroth ◽

Janet K. Jansson ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Acid ◽

Rflp Analysis ◽

Rrna Gene ◽

Bacterial Phyla ◽

Increased Risk ◽

H Pylori ◽

Development Of Gastric Cancer

Persistent infection of the gastric mucosa by Helicobacter pylori can initiate an inflammatory cascade that progresses into atrophic gastritis, a condition associated with reduced capacity for secretion of gastric acid and an increased risk of developing gastric cancer. The role of H. pylori as an initiator of inflammation is evident but the mechanism for development into gastric cancer has not yet been proven. A reduced capacity for gastric acid secretion allows survival and proliferation of other microbes that normally are killed by the acidic environment. It has been postulated that some of these species may be involved in the development of gastric cancer; however, their identities are poorly defined. In this study, the gastric microbiota from ten patients with gastric cancer was characterized and compared with that from five dyspeptic controls using the molecular profiling approach terminal restriction fragment length polymorphism (T-RFLP), in combination with 16S rRNA gene cloning and sequencing. T-RFLP analysis revealed a complex bacterial community in the cancer patients that was not significantly different from that in the controls. Sequencing of 140 clones revealed 102 phylotypes, with representatives from five bacterial phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria). The data revealed a relatively low abundance of H. pylori and showed that the gastric cancer microbiota was instead dominated by different species of the genera Streptococcus, Lactobacillus, Veillonella and Prevotella. The respective role of these species in development of gastric cancer remains to be determined.

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Pathology and pathobiology of the gastric carcinoma

Acta chirurgica iugoslavica ◽

10.2298/aci1101039m ◽

2011 ◽

Vol 58 (1) ◽

pp. 39-52 ◽

Cited By ~ 1

Author(s):

Marjan Micev ◽

Milena Cosic-Micev

Keyword(s):

Gastric Cancer ◽

Gastric Carcinoma ◽

Intestinal Metaplasia ◽

Host Susceptibility ◽

Diffuse Gastric Cancer ◽

Type I ◽

Increased Risk ◽

Spasmolytic Polypeptide ◽

H Pylori ◽

Risk Of Cancer

Recent epidemiological studies in Serbia revealed that gastric carcinoma is the third and the fifth main cause of cancer morbidity in men and women, respectively. Despite the declining incidence of gastric cancer, it remains the second most common cause of cancer-related deaths as it is worldwide. A well-defined carcinogenic inflammation-metaplasia-dysplasia-cancer sequence typically precedes the development of most gastric adenocarcinomas. Alterations such as gastric mucosal atrophy and intestinal metaplasia are merely markers of increased risk, while gastric epithelial dysplasia (GED) represent a direct precursor of cancer. DNA damage and increased mucosal proliferation secondary to H pylori infection, combined with a suitable host susceptibility phenotype (eg, genetic polymorphisms in interleukin IL-1B, IL-1RN, and tumor necrosis factor a TNF-a genes), are important factors in this progression pathway. However, only a small minority of patients infected with H. pylori eventually develops gastric cancer, and eradication of H pylori in these patients does not seem to eliminate the risk of cancer completely. It has been shown that atrophy may be a better indicator of risk of cancer than intestinal metaplasia, and remains to be validated in routine clinical practice according to recent proposal for new quantitative methods. It is often associated with pseudopyloric gland metaplasia in the gastric corpus mucosa, which expresses a type of trefoil peptide, the spasmolytic polypeptide (termed spasmolytic polypeptide-expressing metaplasia or SPEM) and has been shown to be linked more closely to gastric cancer than intestinal metaplasia. Better histological characterization of adenomatous (or type I), hyperplastic (foveolar or type II) and tubule-neck (mucocellular or type III) GED, two-tiered grading system (low and high grade dysplasia) as well as the introduction of Padova and Vienna international classificatons of dysplasia seem to be more helpful in GED survillance and comparative studies. A combination of histopathological features, serum markers such as pepsinogen I, and molecular tests that analyze host susceptibility polymorphisms and bacterial virulence factors, may allow development of strategies for early detection of cancer in the future. At present, pathobiology of gastric cancerogenesis is far from known, despite the progressive knowlegde on predisposing environmental conditions and genetic and epigenetic abnormalities, including tumour supressor genes, oncogenes, microsatellite instability and hypermethylation or the significance of E-cadherin mutational status association with hereditary diffuse gastric cancer syndrome. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as resection margin status and lymph node metastases and their implications have also been discussed. We aim to review these aspects, with special relevance to gastric cancer specimen reporting.

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Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals

International Journal of Molecular Sciences ◽

10.3390/ijms21176451 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6451 ◽

Cited By ~ 2

Author(s):

James W. T. Toh ◽

Robert B. Wilson

Keyword(s):

Gastric Cancer ◽

Ascorbic Acid ◽

Helicobacter Pylori ◽

Vitamin C ◽

Atrophic Gastritis ◽

Chronic Atrophic Gastritis ◽

Gastric Carcinogenesis ◽

Antioxidant Systems ◽

H Pylori

Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

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The Evolving Epidemiology ofHelicobacter pyloriInfection and Gastric Cancer

Canadian Journal of Gastroenterology ◽

10.1155/2003/692808 ◽

2003 ◽

Vol 17 (suppl b) ◽

pp. 18B-20B ◽

Cited By ~ 20

Author(s):

Jia-Qing Huang ◽

Richard H Hunt

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Meta Analysis ◽

Epidemiological Studies ◽

Increased Risk ◽

H Pylori ◽

The Relationship

The relationship betweenHelicobacter pyloriinfection and the risk of gastric cancer has been well established in the last decade. Four metaanalyses have found that the infection increases the risk of noncardia gastric cancer by 2- to 6-fold compared with noninfected control populations. However, the role ofcagAstrains ofH pyloriin relation to gastric cancer has not been evaluated systematically. We undertook a meta-analysis of epidemiological studies examining the relationship between infection withcagA-positive strains ofH pyloriand the risk of gastric cancer, and found that patients who are seropositive forcagAstrains ofH pyloriare at an increased risk for developing noncardia gastric cancer compared with those withH pyloriinfection alone. Therefore, searching forcagA-positive strains ofH pylorimay help identify populations at a greater risk for developing gastric cancer.

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Association of interleukin 12B rs3212227 polymorphism with gastric cancer, intestinal metaplasia, and helicobacter pylori infection

Genetika ◽

10.2298/gensr2001115o ◽

2020 ◽

Vol 52 (1) ◽

pp. 115-126

Author(s):

Seda Orenay-Boyacioglu ◽

Elmas Kasap ◽

Hakan Yuceyar ◽

Mehmet Korkmaz

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Intestinal Metaplasia ◽

Clinical Features ◽

Statistical Significance ◽

Study Groups ◽

Interleukin 12 ◽

Allelic Frequencies ◽

Increased Risk ◽

H Pylori

Interleukin 12 (IL-12) has a key function in promoting Th1 immune response in the gastrointestinal mucosa. Although cytokine gene polymorphisms are associated with increased risk of gastric cancer (GC), studies on different geographic regions and ethnic groups are not able to draw a consistent result. The current case-control study aims to find out an association between a functional IL-12B rs3212227 polymorphism and the susceptibility and clinical features of the study groups, which are GC, Helicobacter pylori-infected and H. pylori-uninfected intestinal metaplasia (IM). In this study, IL-12B rs3212227 polymorphism was genotyped in 35 GC cases, 25 H. pylori-infected IM patients, 25 H. pylori-uninfected IM patients, and 25 control subjects. PCR-RFLP analysis was performed to find out and compare the polymorphism profiles of case biopsies. There was statistical significance in genotype distributions and allelic frequencies in GC patients with proximal arrest in stomach (p=0.042). The rs3212227 genotypes and allelic frequencies were not correlated with any of the study groups (p>0.05). Other clinical features examined in the GC patients were also not correlated with the rs3212227 genotypes and allelic frequencies (p>0.05). Current findings suggest that IL-12B rs3212227 polymorphism may play a role in GC development.

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Helicobacter pylori as a crucial factor in intestinal metaplasia development of gastric mucosa

Advances in Modern Oncology Research ◽

10.18282/amor.v2.i3.72 ◽

2016 ◽

Vol 2 (3) ◽

pp. 173

Author(s):

Sergii Vernygorodskyi

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Intestinal Metaplasia ◽

Chronic Atrophic Gastritis ◽

Gastric Epithelium ◽

Number Of Genes ◽

Activating Transcription Factor ◽

H Pylori ◽

Gene Inhibition

Helicobacter pylori (H. pylori) is detected on the surface of gastric epithelium and in goblet cells, predominantly in patients with chronic atrophic gastritis and incomplete intestinal metaplasia (IM). H. pylori infection persistence leads to the formation of gastrointestinal phenotype of IM. H. pylori can be considered as an etiological factor of IM. It inhibits the expression of SOX2 in gastric epithelial cells, hence activating transcription factor CDX2 as a counterpart to MUC5AC gene inhibition and MUC2 gene induction. Thus, in metaplastic cells, programming differentiation after intestinal phenotype will develop. The role of H. pylori in the origin of intestinal metaplasia of gastric mucosa was defined in this study to elucidate the probable mechanism of cell reprogramming. The activation of CDX2, with simultaneous inactivation and decreased number of genes (e.g., SHH, SOX2, and RUNX3) responsible for gastric differentiation, was identified to cause the appearance of IM.

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