scholarly journals The Relation Between Host TLR9 -1486T/C, rs187084 Gene Polymorphisms and H. Pylori cagA, sodB, hsp60 and vacA Virulence Genes Among Gastric Cancer Patients

Author(s):  
Yasmin Nabiel ◽  
Ragy Shenouda ◽  
Ahmad M Sultan ◽  
Ahmed Shehata ◽  
amira M sultan

Abstract Purpose: To identify different genotypes of TLR9 -1486T/C (rs187084) in patients with gastric cancer and reveal their relation to H. pylori virulence genes (cagA, sodB, hsp60 and vacA). Methods: Patients with gastric cancer were recruited to our study, diagnosed both endoscopically and histo-pathologically. H. pylori strains were isolated from gastric samples by culture and PCR amplification of glmM gene. Virulence genes of H. pylori; cagA, sodB, Hsp60 and vacA, were detected by multiplex PCR. Blood samples were used for genotyping of TLR9 -1486T/C (rs187084) by PCR-RFLP. Results: Out of 132 patients with gastric cancer, 106 (80.3%) were positive for H. pylori by both culture and PCR. Similar number of healthy participants were recruited as controls. The prevalence of virulence genes among the isolated H. pylori were 90.6%, 70.8%, 83.0% and 95.3% for cagA, sodB, hsp60 and vacA respectively. The vacA gene alleles had a prevalence of 95.3% for vacAs1/s2, 52.8% for vacAm1 and 42.5% for vacAm2. The CC genotype of TLR9 -1486T/C had a significantly higher frequency in gastric cancer patients when compared to healthy participants (P = 0.045). Furthermore, the CC genotype demonstrated a significantly higher association with H. pylori strains carrying sodB, hsp60 and vacAm1 virulence genes (P = 0.021, P = 0.049 and P = 0.048 respectively). Conclusions: Patients with CC genotype of TLR9 -1486T/C (rs187084) are at higher risk for development of gastric cancer and its co-existence with H. pylori strains carrying sodB, hsp60 or vacAm1 virulence genes might have a synergistic effect in development of gastric cancer.

2013 ◽  
pp. 11-17
Author(s):  
Thi Tuy Ha Nguyen ◽  
Thi Minh Thi Ha

Background: The role of p53 gene in the gastric cancer is still controversial. This study is aimed at determining the rate of the p53 gene codon 72 polymorphisms in gastric cancer patients and evaluating the relationship between these polymorphisms and endoscopic and histopathological features of gastric cancer. Patients and methods: Sixty eight patients with gastric cancer (cases) and one hundred and thirty six patients without gastric cancer (controls) were enrolled. p53 gene codon 72 polymorphisms were determined by PCR-RFLP technique with DNA extracted from samples of gastric tissue. Results: In the group of gastric cancer, Arginine/Argnine, Arginine/Proline and Proline/Proline genotypes were found in 29.4%, 42.7% and 27.9%, respectively. The differences of rates were not statistically significant between cases and controls (p > 0,05). In males, the Proline/Proline genotype was found in 38.1% in patients with gastric cancer and more frequent in patients without gastric cancer (15.7%, p = 0,01). An analysis of ROC curve showed that the cut-off was the age of 52 in the Proline/Proline genotype, but it was 65 years old in the Arginine/Proline genotype. The Proline/Proline genotype was found in 41.9% in Borrmann III/IV gastric cancer, this rate was higher than Borrmann I/II gastric cancer (16.2%, p = 0.037) and also higher than controls (18.4%, p = 0,01). The rate of Proline/Proline genotype was 41.7% in the diffuse gastric cancer, it was higher than in controls (p = 0,023). Conclusion: No significative difference of rate was found in genotypes between gastric cancer group and controls. However, there was the relationship between Proline/Proline genotype and gastric cancer in males, Borrmann types of gastric cancer, the diffuse gastric cancer. Key words: polymorphism, codon 72, p53 gene, PCR - RFLP, gastric cancer.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 725 ◽  
Author(s):  
Tegshee Tserentogtokh ◽  
Boldbaatar Gantuya ◽  
Phawinee Subsomwong ◽  
Khasag Oyuntsetseg ◽  
Dashdorj Bolor ◽  
...  

Helicobacter pylori infection possessing East-Asian-type CagA is associated with carcinogenesis. Mongolia has the highest mortality rate from gastric cancer. Therefore, we evaluated the CagA status in the Mongolian population. High risk and gastric cancer patients were determined using endoscopy and histological examination. H. pylori strains were isolated from different locations in Mongolia. The CagA subtypes (East-Asian-type or Western-type, based on sequencing of Glu-Pro-Ile-Tyr-Ala (EPIYA) segments) and vacA genotypes (s and m regions) were determined using PCR-based sequencing and PCR, respectively. In total, 368 patients were examined (341 gastritis, 10 peptic ulcer, and 17 gastric cancer). Sixty-two (16.8%) strains were cagA-negative and 306 (83.1%) were cagA-positive (293 Western-type, 12 East-Asian-type, and one hybrid type). All cagA-negative strains were isolated from gastritis patients. In the gastritis group, 78.6% (268/341) had Western-type CagA, 2.9% (10/341) had East-Asian-type, and 18.2% (61/341) were cagA-negative. However, all H. pylori from gastric cancer patients possessed Western-type CagA. Histological analyses showed that East-Asian-type CagA was the most virulent strains, followed by Western-type and cagA-negative strains. This finding agreed with the current consensus. CagA-positive strains were the most virulent type. However, the fact that different CagA types can explain the high incidence of gastric cancer might be inapplicable in Mongolia.


2018 ◽  
Vol 17 (3) ◽  
pp. 41-50
Author(s):  
A. V. Belkovets ◽  
S. A. Kurilovich ◽  
V. N. Maksimov ◽  
Yu. I. Ragino ◽  
L. V. Scherbakova ◽  
...  

Background.A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).The aim:to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.Material and methods.As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and  DNA samples) and data of the population-based registry of GC  (2012) were compared. Gastric cancer patients were matched by  age and sex to HAPIEE population controls. A total of 156 serum  samples (GC – 52, control – 104) and 146 DNA samples (GC – 50,  control – 96) were available for prospective analysis. DNA samples  from 80 gastric cancer patients (45 men and 35 women, mean age  61.0 ± 13.4 years) and from 87 age-and sex-matched controls were  analyzed. DNA samples from venous blood were genotyped  according to standard methods. Serum samples were tested using  diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.Results.No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were  found. A decreased frequency of the Pro allele in female gastric  cancer patients compared with controls indicated that the Pro allele  is protective against the development of gastric cancer, but this  effect was not observed in male patients. No associations of TP53  genotypes with the risk of diffuse or intestinal gastric cancer, as well  as with the age and sex of patients were found. A high frequency of  genotypes with the Pro allele in patients with stage III–IV gastric  cancer indicated the relationship between Arg/Pro TR53 and tumor  progression, in particular, the contribution of the minor Pro allele to  the unfavorable prognosis. A prospective study showed high risk of  reducing the level of pepsinogen for assessing predisposition to  gastric cancer.Conclusion.Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the  TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15521-e15521
Author(s):  
Carlos Castaneda Altamirano ◽  
Carolina Belmar Lopez ◽  
Miluska Castillo Garcia ◽  
Jais Nieves ◽  
Julio Polo ◽  
...  

e15521 Background: Helicobacter pylori (HP) infection is one of the most common infections worldwide and is a risk factor for gastric cancer (GC) development. This study was conducted to determinate the prevalence rate of HP as well as presence of vacA and cagA in gastric cancer samples from Peruvian patients. Methods: GC samples were prospectively collected from patients who went to surgery between April 2015 and November 2016. Three types of gastric samples were obtained from each patient: tumoral area (T), proximal healthy (P) and distal healthy tissue (D) samples. HP status through H&E was analyzed by a pathologist. DNA was extracted from tissue, and detection of colonization (ureA and hspA) and virulence genes (vacA and cagA) of HP was performed through quantitative PCR (qPCR). Results: A total of 183 patients were studied with a mean age of 64 years and 51.9% were men. 52.2% had a primary from antrum, 47.8% was HG 3 and 60% were diffuse. Presence of HP through H&E was found in 58.4% (n=107/183). Positive HP cases through qPCR were determinate with positivity of at least one ureA/hspA gene and was found in 89.6% (n=164/183). HP detection rate and its concentration were higher in D (ureA: 62.8%, n=115, [703.58±245.47pg]; hspA: 73.8%, n=135, [42.77±10.17pg]) than P (ureA: 59.0%, n=108, [539.69±121.32pg]; hspA: 71.0%, n=130, [31.90±8.64pg]) and T (ureA: 49.7%, n=91, [296.32±164.98pg]; hspA: 70.5%, n=129, [4.6±1.33pg]) (p<.001). Antrum location was associated to higher level of hspA expression (p=0.047). Neither histology (p=0.45) nor HG (p=0.2) was associated to level of hspA expression. qPCR detected HP in 75% (n=57/76) of cases without evidence of HP by pathology evaluation (H&E) (ICC: 0.77 vs 0.58). cagA virulence gene was detected in 95.8% (n=159/166) while vacAm allele in 85.5% (n=142/166) and vacAs allele in 96.8% (n=160/166). vacA+cagA- combination was found in 0.6% (n=1/166), vacA+cagA+ cases in 95.8% (n=159/166) and vacA-cagA- cases in 3.6% (n=3/166). Conclusions: Our results show a significant presence of HP in Peruvian gastric cancer patients and combination of vacA+/-cagA+/- virulence genes had particular patterns.


2020 ◽  
Author(s):  
Gang Chen ◽  
Yun Su ◽  
HONG-XIA Gong ◽  
Ling Li ◽  
Zhi-Yi Zhang ◽  
...  

Abstract Gastric cancer is one of the most common malignant tumors of the digestive tract and one of the leading causes of death in patients with malignant tumors worldwide. In recent years, with the deepening of circRNA research, more and more evidence indicates that circRNA plays an important role in the occurrence and development of human malignant tumors. This study firstly conducted a retrospective analysis of the case data of gastric cancer patients who were treated at the Wuwei Cancer Hospital between 2015 and 2017. Subsequently, 18 cases of primary gastric cancer patients and 9 healthy people in Wuwei, Gansu Province were used as controls. The high-throughput microarray technology was used to screen the circRNA expression profiles of healthy and gastric cancer patients, and the expression was expressed by bioinformatics methods. Differential circRNA was used for gene ontology (GO) and KEGG pathway analysis, using its enrichment to predict the relevant biological functions of the differentially expressed circRNA and its involved pathways, and predicting miRNAs interacting with differentially expressed circRNAs, and constructing circRNA-miRNA interaction network. Q-PCR, gene organization microarray and bioinformatics techniques were used to validate candidate differential circRNAs and their linear parental genes and regulatable miRNAs. The results showed that there were 137 circRNAs with significant expression differences (including up-regulation of 67 and down-regulation of 70) in gastric cancer patients, and their differential expression may be related to the occurrence and development of gastric cancer; by GO, KEGG enrichment analysis and Regulating miRNA predictive analysis, the gastric cancer-related GO classification, KEGG Pathway and circRNA-miRNA network were preliminarily obtained, suggesting that differential circRNA may participate in gastric cancer-associated GO classification and KEGG pathway by regulating the expression of parental genes and miRNAs to influence the occurrence and development of gastric cancer. Finally, by using has verified the has_circ_0000437 and its parental genes and regulatable miRNAs, it was found that has_circ_0000437 is highly expressed in gastric cancer patients, and has a certain diagnostic value for the clinical diagnosis of gastric cancer. It may regulate its linear parental gene and The expression of miRNAs affects the development, metastasis and prognosis of clinical gastric cancer.


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