Seroprevalence of Helicobacter pylori Infection in a National Cohort of Veterans With Noncardia Gastric Adenocarcinoma.
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ABSTRACT:
SUBMITTER: Kumar S
PROVIDER: S-EPMC6980451 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Seroprevalence of Helicobacter pylori Infection in a National Cohort of Veterans With Noncardia Gastric Adenocarcinoma.
Kumar Shria S Metz David C DC Kaplan David E DE Goldberg David S DS
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20190720 5
Conventional teaching is that Helicobacter pylori infection is required for the development of non-cardia gastric adenocarcinoma (NCGC) through a sequence of atrophic gastritis, intestinal metaplasia, dysplasia, and finally, cancer.<sup>1-3</sup> However, studies have not demonstrated a 100% rate of H pylori infection in gastric malignancy, hypothesized to be due to false negatives, gastric atrophy leading to apparent loss of infection, and inclusion of cardia, nonintestinal cancers.<sup>1-3</su ...[more]
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Project description:BackgroundBlood-based biomarkers for gastric cancer risk stratification could facilitate targeting screening to people who will benefit from it most. The ABC Method, which stratifies individuals by their Helicobacter pylori infection and serum-diagnosed chronic atrophic gastritis status, is currently used in Japan for this purpose. Most gastric cancers are caused by chronic H. pylori infection, but few studies have explored the capability of antibody response to H. pylori proteins to predict gastric cancer risk in addition to established predictors.MethodsWe used the least absolute shrinkage and selection operator (Lasso) to build a predictive model of noncardia gastric adenocarcinoma risk from serum data on pepsinogen and antibody response to 13 H. pylori antigens as well as demographic and lifestyle factors from a large international study in East Asia.ResultsOur best model had a significantly (P < 0.001) higher AUC of 73.79% [95% confidence interval (CI), 70.86%-76.73%] than the ABC Method (68.75%; 95% CI, 65.91%-71.58%). At 75% specificity, the new model had greater sensitivity than the ABC Method (58.67% vs. 52.68%) as well as NPV (68.24% vs. 66.29%).ConclusionsAlong with serologically defined chronic atrophic gastritis, antibody response to the H. pylori proteins HP 0305, HP 1564, and UreA can improve the prediction of gastric cancer risk.ImpactThe new risk stratification model could help target more invasive gastric screening resources to individuals at high risk.
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Project description:Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta-analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta-analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA.
| S-EPMC4529753 | biostudies-literature
Project description:ObjectiveBoth variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.MethodsWe genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.ResultsThe IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] = 17.76 [6.17-51.06]) or the -592C (OR [95% CI] = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080).ConclusionsInflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.
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Project description:BackgroundRecent experimental studies have suggested a potential link between cathepsin S (CTTS) and gastric adenocarcinoma progression. Herein, we aimed to evaluate the expression of CTTS in gastric adenocarcinoma in patients who underwent curative-intent surgical resection.MethodsThis was a cross-sectional study that included two groups: gastric adenocarcinoma (n = 42) and gastritis (n = 50). The gastritis group was then subdivided into H. pylori-positive (n = 25) and H. pylori-negative (n = 25) groups. Gastric tissue samples were analysed to determine CTTS expression through immunohistochemistry. Samples were obtained by oesophagogastroduodenoscopy or surgical specimens.ResultsIn patients with gastritis, the age ranged from 18 to 78 years. Among them, 34% were male, and 66% were female. In patients with gastric adenocarcinoma, the age ranged from 37 to 85 years. Among them, 50% were male. When comparing the expression of CTTS between the two groups, only 16% of the gastritis samples had an expression higher than 25%. Alternatively, among patients with gastric adenocarcinoma, 19% had expression between 25-50%, 14.3% between 51-75%, and 26.2% had expression higher than 75% (p < 0.001). In the gastritis group, CTTS expression was significantly higher in patients with a positive test for H. pylori than negative test for H. pylori: 87.5% and 38.5%, respectively (p<0.001). There was no statistically significant association between CTTS positivity and clinicopathological variables, including tumour staging, histological type, angiolymphatic invasion, recurrence, current status and death.ConclusionCTTS expression is higher in gastric adenocarcinoma samples. Patients with gastritis due to H. pylori also show a higher expression of CTTS than patients with negative results for this bacterium.
| S-EPMC9135267 | biostudies-literature
Project description:The purpose of the study was to define gastric cell-specific proteomic changes, induced by H. pylori oncogenic strains, that are critical for initiation of the gastric carcinogenic cascade. Gastric cell scrapings were harvested from H. pylori-infected and uninfected animals for quantitative proteomic analyses using isobaric tags for relative and absolute quantitation (iTRAQ). Canonical and disease pathway mapping using Ingenuity Pathway Analysis (IPA) identified significantly altered inflammatory and cancer-signaling pathways that included Rab/Ras signaling proteins.
2018-11-23 | PXD009583 | Pride
Project description:AIM:To investigate the effect of Helicobacter pylori (H pylori) infection on the expressions of Bcl-2 family members in gastric adenocarcinoma. METHODS:Gastric adenocarcinoma and resection margin tissues of 95 patients were studied. Semi-quantitative RT-PCR was used to measure Bid, Bax and Bcl-2 mRNA expressions. RESULTS:Expressions of Bid and Bax in gastric adenocarcinoma tissues without H pylori infection, with cagA- H pylori infection and cagA+ H pylori infection increased significantly in turn (Bid, 0.304, 0.422 and 0.855 respectively, P<0.05; Bax, 0.309, 0.650 and 0.979 respectively, P<0.05). Bcl-2 mRNA levels increased significantly in gastric adenocarcinoma tissues with cagA- H pylori infection and cagA+ H pylori infection, compared with those without H pylori infection (0.696 and 0.849 vs 0.411, P<0.05). Expressions of Bid, Bax and Bcl-2 in resection margin tissues without H pylori infection, with cagA- H pylori infection and cagA+ H pylori infection increased significantly in turn (Bid, 0.377, 0.686 and 0.939 respectively, P<0.05; Bax, 0.353, 0.645 and 1.001 respectively, P<0.05; Bcl-2, 0.371, 0.487 and 0.619 respectively, P<0.05). In H pylori negative specimens, expressions of Bid and Bax correlated negatively with that of Bcl-2 respectively in adenocarcinoma tissues (Bid vs Bcl-2, r=-0.409, P<0.05; Bax vs Bcl-2, r=-0.451, P<0.05). In H pylori positive specimens, expressions of Bid and Bax did not correlate with that of Bcl-2 in adenocarcinoma tissues (Bid vs Bcl-2, r=0.187, P>0.05; Bax vs Bcl-2, r=0.201, P>0.05), but correlated positively with that of Bcl-2 respectively in resection margin tissues (Bid vs Bcl-2, r=0.331, P<0.05; Bax vs Bcl-2, r=0.295, P<0.05). CONCLUSION:H pylori may enhance Bid, Bax and Bcl-2 mRNA levels and cause deregulation of these apoptosis-associated genes expressions, which may play a role during development of gastric adenocarcinoma induced by H pylori.
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Project description:BACKGROUND: Although chemokines have been suggested to play an important role in Helicobacter pylori associated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa. AIMS: To investigate the expression and production patterns of various chemokines using gastric biopsy specimens. METHODS: In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated alpha (GRO alpha)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). cagA gene was identified using PCR. RESULTS: H pylori infection was associated with increased rates of expression of mRNA for IL-8, GRO alpha, RANTES, and MIP-1 alpha and with increased levels of mucosal IL-8 and GRO alpha. IL-8 and GRO alpha levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pylori infection was associated with increased rates of expression of mRNA for IL-8 and GRO alpha and with increased levels of these chemokines. CONCLUSION: H pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GRO alpha), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach.
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Project description:BackgroundAlthough gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence.Methods and findingsWe developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men.ConclusionsTrends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts.
| S-EPMC3660292 | biostudies-literature
Project description:ObjectiveInfection with Helicobacter pylori (H pylori), especially cytotoxin-associated gene A-positive (CagA+) strains, has been associated with various gastrointestinal and extragastric diseases. The aim of this study was to characterize H pylori-induced alterations in the gastric and tongue coating microbiota and evaluate their potential impacts on human health.DesignThe gastric mucosa and tongue coating specimens were collected from 80 patients with chronic gastritis, and microbiota profiles were generated by 16S rRNA gene sequencing. Samples were grouped as H pylori negative (n = 32), CagA-negative H pylori infection (n = 13), and CagA-positive H pylori infection (n=35). The comparison of bacterial relative abundance was made using a generalized linear model. Functional profiling of microbial communities was predicted with PICRUSt and BugBase. Microbial correlation networks were produced by utilizing SparCC method.ResultsSignificant alterations of the gastric microbiota were found in the H pylori+/CagA+ samples, represented by a decrease in bacterial diversity, a reduced abundance of Roseburia, and increased abundances of Helicobacter and Haemophilus genera. At the community level, functions involved in biofilm forming, mobile element content, and facultative anaerobiosis were significantly decreased in gastric microbiome of the H pylori+ subjects. The presence of CagA gene was linked to an increased proportion of Gram-negative bacteria in the stomach, thereby contributing to an upregulation of lipopolysaccharide (LPS) biosynthesis. The number of bacterial interactions was greatly reduced in networks of both tongue coating and gastric microbiota of the H pylori+/CagA+ subject, and the cooperative bacterial interactions dominated the tongue coating microbiome.ConclusionsInfection with H pylori strains possessing CagA may increase the risk of various diseases, by upregulating LPS biosynthesis in the stomach and weakening the defense of oral microbiota against microorganisms with pathogenic potential.
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Project description:Gastric cancer is a world health problem and depicts the fourth leading mortality cause from malignancy in Mexico. Causation of gastric cancer is not only due to the combined effects of environmental factors and genetic variants. Recent molecular studies have transgressed a number of genes involved in gastric carcinogenesis. The aim of this review is to understand the recent basics of gene expression in the development of the process of gastric carcinogenesis. Genetic variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved in mediating inflammation have been associated with the development of gastric carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, β-catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha, GSK3β, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX-2) have been studied in association with oncogenic activation or inactivation of tumor suppressor genes. All these mechanisms have been investigated to elucidate the process of gastric carcinogenesis, as well as their potential use as biomarkers and/or molecular targets to treatment of disease.
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