Interaction of HULC polymorphisms with Helicobacter pylori infection plays a strong role for the prediction of gastric cancer risk

2020 ◽  
Vol 16 (26) ◽  
pp. 1997-2006
Author(s):  
Ben-Gang Wang ◽  
Han-Xi Ding ◽  
Zhi Lv ◽  
Qian Xu ◽  
Yuan Yuan
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Susceptibility ◽  
Single Gene ◽  
Recessive Model ◽  
Nucleotide Polymorphisms ◽  
Gene Environment ◽  
Experimental Expression ◽  
H Pylori ◽  
2D Model

Aim: Gene–environment interactions have better efficacy in predicting cancer susceptibility than a single gene. Materials & methods: Eight tag single nucleotide polymorphisms encompassing the whole HULC gene were detected by KASP platform (LGC Genomics, Hoddesdon, UK) in 631 gastric cancer (GC) cases and 953 controls. Results: The HULC gene rs7770772 polymorphism could increase GC risk (recessive model: odds ratio = 1.95). The multifactor dimensionality reduction (MDR) analysis suggested that the 2D model HULC rs7770772– Helicobacter pylori had better effect on GC risk prediction (maximum testing accuracy = 0.7005). No significant result was observed in our experimental expression quantitative trait loci analysis. Conclusion: 2D model HULC rs7770772– H. pylori might have superior efficacy for GC risk than a single factor.

scholarly journals Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Ni ◽  
Anlai Ji ◽  
Junfeng Yin ◽  
Xiangjun Wang ◽  
Xinnong Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Potential Effect ◽  
Recessive Model ◽  
Dominant Model ◽  
Common Snps ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk

Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk.Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI).Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model.Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect.

scholarly journals HOTTIP polymorphism may affect gastric cancer susceptibility by altering HOTTIP expression

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Ben-gang Wang ◽  
Yi-zhi Li ◽  
Han-xi Ding ◽  
Zhi Lv ◽  
Qian Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Disease Risk ◽  
Cancer Susceptibility ◽  
Recessive Model ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Specific Pcr ◽  
Non Coding Rna

Abstract Background: Non-coding RNA polymorphisms can affect disease risk and prognosis by influencing gene expression. Here, we first investigated the association between single nucleotide polymorphisms (SNPs) of long non-coding RNA (lncRNA) HOTTIP and gastric cancer risk/prognosis. Methods: A total of five HOTTIP SNPs among 627 gastric cancer cases and 935 controls were tested by Kompetitive Allele Specific PCR (KASP) assay. The functional SNPs underwent eQTL analysis and the expression of HOTTIP was assessed by quantitative RT-PCR. Results: The rs2067087 and rs3807598 SNPs of HOTTIP increased susceptibility to gastric cancer (rs2067087: dominant model, P=0.008, odds ratio (OR) = 1.35; rs3807598: recessive model, P=0.037, OR = 1.29). Both HOTTIP rs2067087 and rs3807598 could affect the expression of mature lncRNA (P=0.003 and P=0.032, respectively). Conclusion: The rs2067087 and rs3807598 SNPs of HOTTIP are associated with gastric cancer risk, possibly by affecting the expression of mature HOTTIP.

Association of microRNA Polymorphisms with the Risk of Gastric Cancer in a Romanian Population

2017 ◽  
Vol 26 (3) ◽  
pp. 231-238 ◽  
Author(s):  
Ion Rogoveanu ◽  
Florin Burada ◽  
Mihai Gabriel Cucu ◽  
Cristin Constantin Vere ◽  
Mihai Ioana ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Genetic Model ◽  
Cancer Susceptibility ◽  
Statistical Significance ◽  
Recessive Model ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Single Nucleotide ◽  
Gastric Cancer Patients

Background & Aims: MicroRNAs (miRNAs) play an important role in the occurrence and progression of human cancers, including gastric cancer. Our hospital-based case-control study aimed to investigate whether four commonly studied single nucleotide polymorphisms (SNPs) have effects on susceptibility to gastric cancer in a Romanian population.Method: We genotyped the miR-27a rs895819, miR-146a rs2910164, miR-196a2 rs11614913 and miR-499 rs3746444 SNPs by real-time PCR using predesignated TaqMan assays in 430 individuals (142 gastric cancer patients and 288 age and gender matched cancer-free controls). The associations between the investigated miRNA SNPs and gastric cancer risk were assessed by odds ratio (OR) with 95% confidence interval (CI) using logistic regression analysis.Results: A higher frequency of the miR-27a rs895819 CC genotype (OR 1.98, 95% CI: 1.05-3.73, p=0.036) was found in the patients with gastric cancer compared with the controls. Similar results were observed in a recessive model, the CC genotype was correlated with gastric cancer susceptibility (OR 1.95, 95% CI: 1.07-3.55, p=0.032). In the stratified analysis, the association between miR-27a rs895819 SNP and gastric cancer risk was limited to noncardia (OR 2.08, 95% CI: 1.10-3.94, p=0.027) and intestinal (OR 2.27, 95% CI: 1.05-4.92, p=0.042) subgroups. However, after Bonferroni correction, all associations described above lost statistical significance. No correlation was observed for the remaining SNPs and risk of gastric cancer in any genetic model studied.Conclusion: This study showed no association of the investigated miRNA SNPs with the risk of gastric cancer in a Romanian population.Key words:  –  –  – .Abbreviations: GC: gastric cancer; miRNA: microRNA; SNP: single nucleotide polymorphism.

scholarly journals The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection

2015 ◽  
Vol 49 (3) ◽  
pp. 256-264 ◽  
Author(s):  
David Stubljar ◽  
Samo Jeverica ◽  
Tomislav Jukic ◽  
Miha Skvarc ◽  
Tadeja Pintar ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Chronic Gastritis ◽  
Gene Polymorphisms ◽  
Inflammatory Responses ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Slovenian Population ◽  
Significant Difference ◽  
H Pylori

Abstract Background. Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population. Patients and methods. In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1rα, TNF-α, TLR-4) in all subjects. Results. We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233―1.329) and for chronic gastritis 2.073 (95% CI: 1.005―4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583―9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583―3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626―3.139). Other alleles had OR less than 1. Conclusions. We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.

Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

2020 ◽  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Cancer Stem Cells ◽  
Histopathological Examination ◽  
Physiological Saline ◽  
Rrna Gene ◽  
Peptic Ulcers ◽  
Gastric Cancer Stem Cells ◽  
H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

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 Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 181
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Eisaburo Sueoka ◽  
In Kyoung Lim ◽  
Hirota Fujiki
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cell Surface Receptor ◽  
Tumor Promoter ◽  
Cancer Development ◽  
Human Gastric Cancer ◽  
Tnf Α ◽  
Surface Receptor ◽  
H Pylori ◽  
Factor Α

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

scholarly journals Diversity of 3′ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Amino Acid ◽  
Chinese Population ◽  
Statistical Difference ◽  
Variable Region ◽  
Repeat Region ◽  
Geographical Regions ◽  
H Pylori ◽  
Epiya Motifs

Abstract Background The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases. Methods A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software. Results A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004). Conclusions In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.

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