Survey on Awareness of Helicobacter pylori and Gastric Cancer in the Japanese Population Using an Internet Survey.

AGA Institute Quality Measure Development for the Management of Gastric Intestinal Metaplasia With Helicobacter pylori

Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase alpha subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, and prostaglandin E(2). Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27(Kip1). We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation.

Background: Korea has a high incidence of gastric cancer and a high prevalence of Helicobacter pylori infection. Observation of prevalence trends and determination of risk factors for gastric cancer are important to establish health policies to prevent and reduce the burden of disease. Currently, there is no evidence of complete correlation between prevalence of H. pylori infection and the occurrence of gastric cancer. Several explanations have been proposed for the paradox of high prevalence of infection and low gastric cancer incidence in certain places, including diet and salt consumption, genetic susceptibility, other infections, aflatoxin-contaminated food, and the interaction of all these factors, but none of them has been clearly established. Aim: To explore the potential effects of prevalence of H. pylori infection and other risk factors on gastric cancer incidence in Korea. Methods: Information on gastric cancer incidence, prevalence of H. pylori infection, and the risk factors for gastric cancer were evaluated from nationally representative data - the Korean National Cancer Registry, nationwide routine health check-up surveillance system, and National Health and Nutrition Survey, respectively. Secular trends of H. pylori infection prevalence and age-standardized incidence rates for gastric cancer by region were examined. Furthermore, trends of income level, education level, marital status, number of family members, smoking status, drinking status, obesity, diabetes, hypertension, dyslipidemia, and age-standardized incidence rates for gastric cancer by region were examined. Results: Gastric cancer incidence showed a decreasing trend from 2011 to 2015; 50.6%–44.4% for men and 22.1%–17.0% for women. The prevalence of H. pylori infection also showed a decreasing trend; from 66.9% in 1998%–54.4% in 2011. In Korea, areas with high prevalence of H. pylori infection also showed high gastric cancer incidence. However, the Chungcheong area showed relatively low prevalence of H. pylori infection, but had the highest gastric cancer incidence in Korea. Other factors which showed similar effects on gastric cancer incidence, like H. pylori infection were large family size (4 or more family members), low income, low education, and obesity. The effect of introduction of 'National Cancer Screening Program' will be evaluated in the final outcome. Conclusion: The results of this study indicated that significant regional differences exist between trends in H. pylori infection prevalence and gastric cancer incidence in Korea. Also, the possibility of lack of association between H. pylori prevalence and the incidence of gastric cancer are suggested. Overall, this study suggests the need for further research to explore potential factors accounting for regional differences in gastric cancer incidence in Korea.

A Summary of the 2020 Gastric Cancer Summit at Stanford University

Helicobacter pylori is a human pathogen that infects the stomach. More than half of the human population is infected with H. pylori, which is major cause of peptic ulcers, gastric cancers and mucosa-associated lymphoid tissue lymphoma. However, the majority of patients infected with H. pylori generally remain asymptomatic and never develop significant disease. H. pylori has high genetic diversity, and different genotypes of H. pylori are involved in different gastroduodenal disorders. The hosts’ genetic factors also influence the development of peptic ulcers and gastric cancer, and plenty of evidence has demonstrated that genetics plays a role in susceptibility and contributes to the differences between those who develop H. pylori infection, peptic ulcers and gastric cancer.1–3 Numerous single nucleotide polymorphism (SNP) studies have been undertaken to identify candidate genes that most likely play a role in the development of peptic ulcers and gastric cancer.4–8 Recently, a genome wide association study (GWAS) and next generation sequencing study identified several genetic loci that confer susceptibility for H. pylori infection and gastroduodenal disease.9,10 H. pylori prevalence is as high as 90% in some countries, but approximately 5% to 10% of a given population is never infected with H. pylori, even in the presence of high exposure rates.9 A GWAS meta-analysis identified an association between Toll-like receptor 1 (TLR1) and H. pylori seroprevalence, suggesting that genetic variations in TLR1 may explain some of the observed variations in individual risk for developing H. pylori infection.9 The pathogenesis of different clinical outcomes is multifactorial and includes the virulence of H. pylori, environmental factors and host factors. Different types of H. pylori virulence factors (CagA, VacA1, babA2, and OipA) result in different prevalence rates of gastroduodenal disease in different geographic areas. Genetic polymorphisms in the hosts’ interleukin (IL)-10, tumor necrosis factor α (TNF-α), IL-IB and IL-1RN genes have served as important candidates.3–8 IL-10 is an anti-inflammatory cytokine that downregulates cell-mediated immune responses and cytotoxic inflammatory responses. An IL-10 promoter polymorphism is associated with an increased risk of developing a peptic ulcer and gastric cancer. A hallmark of H. pylori-triggered mucosal inflammation is the continuous recruitment of neutrophils and mononuclear cells to the gastric lamina propria. TNF-α plays a crucial role in the host’s immunological defense against H. pylori infection. A TNF-α promoter SNP has been shown to be associated with an increased risk for the development of atrophic gastritis, peptic ulcers and gastric cancer. While the TNF-α 1031 and 863 promoter SNPs are significant risk factors for peptic ulcer in combination with H. pylori infection in Taiwan,1 neither TNF-α 1031 nor 308 TNF-α is a risk factor for peptic ulcer after H. pylori infection in the Polish population.10 In China, IL-B-511, IL-RN, and TNF-α 308 polymorphisms are not associated with the development of duodenal ulcers.8 In Israel, the H. pylori iceA1 bacterial strain is associated with duodenal disease in children, and a TNF-α 238 G polymorphism has been found to be a risk factor for the development of peptic ulcers in children infected with H. pylori.5 In Japan, polymorphisms in interferon-α, rather than IL-1β, are associated with an increased risk of developing gastric ulcers and cancer.4 A GWAS that compared samples form duodenal ulcers and healthy controls in Japan identified two susceptible loci at the prostate stem cell antigen gene at the 8q24 and a locus at the ABO blood group gene at 9q34.11 In Korea, several studies have been undertaken to determine the role of polymorphisms in the IL-10 and TNF-α promoter genes in the development of peptic ulcers and gastric cancer. The IL-10-1082/592 and TNF-α 308 genetic polymorphisms were not found to be important risk factors for peptic ulcers and gastric cancer in Korea.6 However, genetic polymorphisms in IL-1B and IL-1RN contribute to the development of gastric ulcers and gastric cancer after H. pylori infection.7 H. pylori is a strong risk factor for gastric cancer. However, only a small portion of H. pylori-infected subjects eventually develop gastric cancer. Gastric carcinogenesis is affected by several factors, including the strain of H. pylori, environmental factors (smoking, high salt intake, and so forth) and host genetics. IL-10 polymorphisms (819C and 592C alleles have complete linkage disequilibrium with 819T) are associated with H. pylori infection and smoking, which increase the risk of developing noncardia gastric cancer, especially intestinal type, in Korea.3 In conclusion, host genetic polymorphisms, investigating currently known SNPs, the virulence of H. pylori and ethnic and regional differences should be considered when assessing the risk factors for the development of gastric ulcers and cancer.

Gastric cancer has been consistently decreasing worldwide, whereas cardia gastric cancer is on the rise. This indicates that the exposure rates to epidemiological causes are changing. In this study, we aim to review the risk factors for gastric cancer with respect to cardia and non-cardia types. One of the most significant risk factors for gastric cancer is Helicobacter pylori infection. H. pylori infection is known as a risk factor for non-cardia gastric cancer, and there have been results indicating that H. pylori infection is not associated with cardia gastric cancer. However, in the East Asian region, there is epidemiological evidence suggesting that H. pylori infection might be a risk factor for cardia gastric cancer. Smoking and alcohol consumption are known risk factors for gastric cancer, regardless of anatomical location. Obesity is considered a factor in the development of cardia gastric cancer. However, further research is needed to understand the specific relationship with non-cardia gastric cancer. The consumption of high-salt and processed meat is more distinctly associated with non-cardia gastric cancer than in cardia gastric cancer. In addition to these factors, exposure to chemicals and radiation are considered risk factors for gastric cancer. Primary prevention of gastric cancer involves eliminating or avoiding risk factors such as H. pylori eradication and adopting a healthy lifestyle, including quitting smoking, reducing alcohol consumption, maintaining a healthy weight, and having a low-salt diet.

Esophageal Cancers and Helicobacter pylori: Do Host Genes Matter?

Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95–4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58–3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46–0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies.

To investigate the correlation between gastric xanthoma (GX) and precancerous lesions (PCL) and gastric cancer (GC), and to explore other potential risk factors for PCL and GC in northwest China. A case-control study was conducted from September 2022 to September 2023 at Xijing Hospital, Air Force Medical University (Xi'an, Shaanxi Province, China). The patients who underwent gastroscopy were enrolled and divided into the chronic gastritis (CG) group (n = 423), PCL group (n = 422), and GC group (n = 415). The variables were selected through univariate analysis, including demographic information, dietary habits, lifestyle, gastroscopic findings, and Helicobacter pylori (H. pylori) infection. Multivariate logistic regression analysis was performed to analyze the factors associated with PCL and GC, and odds ratio (OR) and 95% confidence interval (CI) were calculated. GX was more prevalent in the PCL group (14.93%) and the GC group (19.76%) than in the CG group (6.15%). Multivariate analysis revealed that age ≥ 50 years, male gender, rural residence, H. pylori infection, family history of GC, GX, and hypertension were independent risk factors for GC and PCL. Furthermore, a diet high in salt and spice, coupled with daily intake of less than 100 g of fresh fruits, might be associated with the occurrence of GC. Age ≥ 50 years, male gender, rural residence, family history of GC and H. pylori infection, presence of GX, and a history of hypertension may be risk factors for PCL and GC.

Appropriate interval of surveillance endoscopy for early detection of gastric cancer.

Regulation of Gastric Carcinogenesis by InflammatoryCytokines.

Helicobacter pylori (H pylori) infection is a known risk factor for gastric cancer (GC) and has been linked with gastroesophageal junction (GEJ) cancer. Studies examining the relationship between H. pylori infection, GC characteristics and prognosis are limited and have yielded conflicting results. We report on the clinicopathologic characteristics and oncologic outcomes of gastric and GEJ cancer patients with and without a history of H. pylori treated at our institution. We retrospectively reviewed the medical records of patients over the age of 18 years who underwent curative resection for GEJ and GC at Mount Sinai Hospital between 2007 and 2012 who had histopathologic documentation of the presence or absence of H pylori infection. Demographic, clinical, pathologic, treatment characteristics and outcomes including recurrence-free survival (RFS) and overall survival (OS) were compared. Ninety-five patients were identified. The majority of patients were male (61%), white (36%) or Asian (34%), with median age at diagnosis 64. Tumors were stage I (51%), stage II (23%), stage III (25%), and stage IV (1%). H pylori infection status was documented at the time of cancer diagnosis in 89 (94%) patients, and following cancer diagnosis and treatment in 6 (6%) patients. Younger age at diagnosis, Asian race and Lauren histologic classification were associated with H Pylori infection. H pylori positive patients exhibited higher 5-year OS and 5-year RFS compared to H pylori negative patients, though the difference was not statistically significant in either univariate or multivariate analyses. In this retrospective series of predominantly early stage GC and GEJ cancers, H. pylori positive patients were significantly younger at cancer diagnosis and were more frequently Asian compared to H. pylori negative patients. Other demographic and histologic classifications except for Lauren histologic classification were similar between the two groups. H pylori positive patients appeared to have improved outcomes compared to H. pylori negative patients.

Mutational Signatures in Helicobacter pylori–induced Gastric Cancer: Lessons From New Sequencing Technologies

Helicobacter pylori (H. pylori) infection has been recognized as a human class I carcinogen in 1994 and linked with the development of gastric cancer in numerous studies. Gastric cancer still ranks as the second leading mortality cause among all cancers in the world and in the fourth place in Europe. High prevalence of H. pylori infection and high incidence of gastric cancer in adults are still characteristic of the Baltic States and resemble patterns in the Western and Northern European countries several decades ago. The recent decline in gastric cancer incidence and mortality as well as H. pylori prevalence in Lithuania, Latvia and Estonia reflects the worldwide trends. H. pylori induced diseases, however, still remain a significant burden for health care systems in the Baltic States. The relevance of H. pylori induced gastric diseases in the Baltic States has stimulated epidemiological, clinical as well as fundamental research on H. pylori infection, premalignant gastric conditions and gastric cancer. This paper reviews original research on H. pylori infection and related diseases in Lithuania, Latvia and Estonia during the period 1992–2011. Keywords: Helicobacter pylori, atrophic gastritis, gastric cancer, Baltic States

Background Helicobacter pylori (H. pylori) infection is a significant risk factor for gastric cancer, particularly in developing countries like Yemen, where the prevalence is high. This study aims to investigate the relationship between H. pylori infection and types of tumor markers (CEA and CA19-9) among Yemeni gastric cancer patients, comparing the frequency of these markers in patients with and without H. pylori infection. Methods A case-control study was conducted in Sana’a, Yemen, between January 2022 and December 2023. A total of 170 gastric cancer patients were enrolled, divided into two groups: 85 patients with H. pylori infection (cases) and 85 without (controls). Serum levels of CEA and CA19-9 were measured using enzyme-linked immunosorbent assay (ELISA). Results The frequency of CEA and CA19-9 was measured in both groups. The median CEA levels were 7.05 ng/mL in H. pylori positive group and 7.14 ng/mL in negative group. The median CA19-9 levels were 33 U/mL in H. pylori positive group and 32 U/mL in negative group. No significant differences were found in the serum levels of CEA (p = 0.44) or CA19-9 (p = 0.94) between the two groups. However, a significant association was observed between H. pylori infection and gastric cancer site in cardia and fundus regions (p = 0.047). Conclusion This study found no significant association between H. pylori infection and types of tumor markers (CEA and CA19-9) among Yemeni gastric cancer patients. However, the significant association between H. pylori infection and site of gastric cancer in cardia and fundus regions needs further investigations to reveal the associated mechanisms.