Gastric cancer and human leukocyte antigen: distinct DQ and DR alleles are associated with development of gastric cancer and infection by Helicobacter pylori (original) (raw)
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International Journal of Cancer, 2009
It has been reported that polymorphisms of human leukocyte antigen (HLA) genes and several cytokine genes are associated with an increased risk of developing gastric cancer (GC). However, the results of studies from different geographic regions, ethnic groups and study groups are inconsistent. The aim of this study was to evaluate the influence of H. pylori infection and host genetic factors on GC susceptibility in Japanese patients with GC. We analyzed genotypes for HLA class I and II, tumor necrosis factor a, interleukin (IL)-1b, IL-1 receptor, IL-4, IL-4Ra and IL-10 in 330 H. pyloriinfected noncardia patients with GC and 190 H. pylori-infected nonulcer dyspeptic controls. Haplotype analyses indicated that the frequencies of the HLA DRB1*0405 and DQB1*0401 alleles were increased in the patients with intestinal-type GC when compared with controls (both DRB1*0405 and DQB1*0401: p 5 0.015, OR 5 1.57, 95% CI 5 1.09-2.26), but the changes were not statistically significant after correction for multiple comparisons. None of the cytokine gene polymorphisms were associated with GC susceptibility, whether patients with GC were analyzed as a group according to the histological subtype. Of interest was the comparison of controls and patients with intestinal-type GC. The frequency of an IL-10-592AA homozygote showing concomitant carriage of the HLA DRB1*0405-DQB1*0401 haplotype was significantly higher in patients with intestinal-type GC (v 2 5 6.369, p 5 0.0116, p c 5 0.0464, OR 5 2.43, 95% CI 5 1.21-4.48). Our results suggest that the HLA class II and IL-10-592A/C polymorphisms synergistically affect the susceptibility to GC development of H. pylori-infected individuals in the Japanese population. ' 2009 UICC Gastric cancer (GC) remains one of the most frequently diagnosed malignant diseases worldwide, and even more so in Japan. Several studies have shown that Helicobacter pylori infection is an important risk factor for GC. Although about half of the world's population is believed to be infected with H. pylori, only a small proportion of those people develop GC, suggesting that additional factors such as host genetic factors and environmental factors, as well as the diversity of H. pylori virulence genes, must be involved in the development and progression of GC. Therefore, this belief has generated interest in host factors, especially immune-and inflammatory-related host genetic factors.
Association between Helicobacter pylori hopQI genotypes and human gastric cancer risk
Cellular and molecular biology (Noisy-le-Grand, France), 2016
The Helicobacter pylori use a number of mechanisms to survive in the stomach lumen and can lead to gastritis and reduction in stomach acid secretion. It has been found that the risk of developing gastric carcinoma is associated to heterogeneity of H. pylori virulence factors such as HopQ. The HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also main role in the virulence of H. pylori. The purpose of the current study was to investigate the association between different H. pylori virulence hopQI (types I) genotyping and patients with gastroduodenal disorders. For this purpose 58 stomach biopsies of the patients with gastric cancer and 100 saliva samples from healthy and H. pylori infected individuals were collected and studied. Then genomic DNA was purified and PCR was done for desired gene via specific primers. The H. pylori infections were diagnosed using PCR for GlmM gene. Then frequencies of hopQI+ and hopQI- ...
Infection, Genetics and Evolution, 2020
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Helicobacter pylori hopQ alleles (type�I and�II) in gastric cancer
Biomedical Reports, 2016
The Helicobacter pylori (H. pylori) outer membrane protein (HopQ) of is one of the proteins involved in bacterial adherence to gastric mucosa and has been suggested to have a role in the virulence of H. pylori. The aim of the present study was to determine the association between H. pylori virulence types I and II hopQ genotypes and patients with different gastrointestinal diseases. A polymerase chain reaction-based assay was used to determine the presence of type I and type II hopQ genes in 88 H. pylori strains isolated from H. pylori-infected patients. Of the total 88 H. pylori isolates, type I and type II hopQ alleles were detected in 52 (59.1%) and 36 (40.9%), respectively. A significant association was found between type I hopQ gene and gastric cancer [odds ratio, 2.3; 95% confidence interval (CI), 1.3-4.1] and gastric ulcers (odds ratio, 2.5; 95% CI, 1.4-4.3). A significant association was also identified between the type II hopQ gene and gastric cancer (odds ratio, 2.4; 95% CI, 1.1-3.0). The association between hopQ type I and hopQ type II genotypes and clinical status suggest that these genes may be helpful in the universal prediction of specific disease risks.
Cytokine, 2017
Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms +114 T > G (rs2069763) and −330 T > G (rs2069762) and the development of gastric cancer; these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). PCR-RFLP was used to characterize the +114 T > G and −330 T > G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR = 6.43, 95% CI: 1.47-28.10, p = 0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR = 4.47, 95% CI: 1.84-10.84, p = 0.0022). When the IL-2 +114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR = 5.97, 95% CI: 1.60-22.27, p = 0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR = 6.36, 95% CI: 2.66-15.21, p < 0.0001). The haplotype was also analyzed. The −330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the −330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the −330G/+114T haplotype.
Gastric Cancer, 2010
A (cagA)-positive Helicobacter pylori, resulting in the accumulation of alterations in the TP53 tumor suppressor gene in gastric cells. We investigated the association of the AICDA 7888 C/T polymorphism with H. pylori infection and the risk of gastric cancer and atrophic gastritis in Japanese subjects. Methods. The study subjects were 583 histologically diagnosed gastric cancer patients (cases) and 1637 age-and sexfrequency-matched control outpatients, who visited Aichi Cancer Center Hospital from the years 2001 to 2005. In the controls, serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and atrophic gastritis, respectively. Odds ratios (ORs) and 95% confi dence intervals (CIs) were calculated by a logistic model.
HLA-DQA1 genotyping of Helicobacter pylori associated gastritis patients
DNA, 2010
To study HLA-DQA1 genotyping in Helicobacter pylori associated gastritis patients. This study was carried out in College of Medicine, University of Basrah. HLA-DQA1 genotyping was done in College of Medicine, University of Manitoba, Winnipeg, Canada during the period from 17th of April 2009 to 15th of July 2010. A total of 100 patients (41 males and 59 females and a total of 30 controls (18 males and 12 females) were included in this study. DQA1 alleles frequencies were studied in 70 H. pylori associated gastritis patients and 30 healthy controls. DQA1*0201 decreased allele frequency was statistically not significant in H. pylori associated gastritis patients, but there was a strong association (odds ratio= 2.61 , as compared with controls. In the present study many alleles from both locus showed high frequencies with a very strong association, but statistically not significant, this association has not been reported and it is important to note that a larger sample size should be studied.
Genetic predisposition to Helicobacter pylori-induced gastric precancerous conditions
World journal of gastrointestinal oncology, 2010
Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helicobacter pylori (H. pylori) infection (e.g. TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gast...
Seroreactivity to Helicobacter pylori antigens as a risk indicator of gastric cancer
Background: Multiple etiologic factors are suspected to cause gastric cancer, the most important of which is infection with virulent types of Helicobacter pylori. Materials and Methods: We have compared 102 gastric cancer patients with 122 non-ulcer, non-cancer dyspeptic patients. Gastric specimens were evaluated for H. pylori infection by tissue-based detection methods. Patient sera underwent antigen-specific ELISA and western blotting using a Helicoblot 2.1 kit and antibody responses to various H. pylori antigens were assessed. Results: The absolute majority (97-100%) of both groups were H. pylori seropositive. Multivariate regression analysis demonstrated serum antibodies to the low molecular weight 35kDa protein to be protective and reduce the risk of gastric cancer by 60% (OR:0.4; 95%CI:0.1-0.9). Conversely, seroreactivity to the 89kDa (VacA) protein was significantly higher in gastric cancer patients (OR:2.7; 95%CI:1.0-7.1). There was a highly significant association (p<0.001) between seroreactivity to the 116kDa (CagA) and 89kDa (VacA) proteins, and double positive subjects were found at nearly five fold (OR:4.9; 95%CI:1.0-24.4) enhanced risk of gastric cancer as compared to double negative subjects. Conclusions: Seroreactivity to H. pylori low (35kDa) and high (116kDa/89kDa) molecular weight antigens were respectively revealed as protective and risk indicators for gastric cancer.