The prevalence and risk factors of Helicobacter pylori infection and cagA virulence gene carriage in adults in the Navajo Nation.

Background. The Navajo Nation, the largest tribe in the United States (US), is experiencing a high burden of stomach cancer, possibly due to a high prevalence of Helicobacter pylori (Hp) infection. Hp is a major risk factor for stomach cancer and Hp strains that carry the cagA-gene are linked to greater gastrointestinal disease severity. Yet little research has investigated the prevalence and correlates of Hp and cagA infection in Navajo people. We assessed the prevalence and correlates of Hp infection and cagA-gene carriage in adult tribal members residing in the Navajo Nation. Methods and Material. We conducted a community-based cross-sectional study in the Navajo Nation in 2021 during the COVID-19 pandemic. Participants were recruited using online and offline platforms, including social media, a study website, newspaper advertisements, flyers, word of mouth, and community outreach. Stool samples collected from participants were analyzed with droplet digital PCR for Hp 16S and cagA virulence genes. Demographic characteristics, health, and dietary factors were collected from self-administered health and food questionnaires sent via mail. Results. Of 99 participants, half (49.5%) were 18-44 years old and 73.7% were female. About sixty percent (57.7%, 95% CI: 47.6-67.3) of participants were infected with Hp, twice the US population prevalence (27%). Among Hp-infected participants, 76.7% (95% CI: 64.0-86.6) were cagA-gene positive, four times the cagA gene prevalence in White people (19%). Controlling for age and sex, monthly use of Navajo herbal medicines was positively associated with Hp infection (OR=3.73, 95% CI: 1.05-17.87). No significant associations with Hp and cagA-gene were observed with other risk factors such as older age, males, lower education, and high sodium intake. Conclusion. A substantial proportion of Navajo adults in our study had Hp and cagA-positive infections. Given studies showing the antibacterial activity of Indigenous herbal medicines, monthly use of Navajo herbal medicines was an unexpected risk factor for Hp infection. This observation may be due to reverse causality, where participants with gastrointestinal conditions used Navajo herbal medicines for gastrointestinal symptom relief, particularly when participants had limited access to healthcare services due to the COVID-19 pandemic. Possible environmental transmission of Hp in the preparation of herbal medicines (i.e., water source, utensils) could be another source of exposure. Given the high burden of Hp and cagA-positive infections, culturally tailored health education strategies and interventions addressing these infections present an opportunity for research and cancer prevention among Navajo adults. Citation Format: Dornell Pete, Nina R. Salama, Johanna W. Lampe, Michael C. Wu, Amanda I. Phipps. Addressing stomach cancer disparities by assessing Helicobacter pylori infections among American Indian adults from the Navajo Nation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3944.

Effects of Helicobacter pylori and Nonsteroidal Anti-Inflammatory Drugs on Peptic Ulcer Disease: A Systematic Review

A substantial burden of stomach cancer continues to be observed in American Indians (AI) in the Southwestern United States. The Navajo Nation, the largest tribe in the Southwest, is experiencing higher incidence of stomach cancer compared to the general population in the region, possibly due to high prevalence of Helicobacter pylori (H. pylori) infection and other contributing factors, like diet. To learn about factors linked to stomach cancer, we initiated a cross-sectional study to determine the prevalence, virulence, and dietary correlates of H. pylori infection among Navajo adults. We hypothesized that H. pylori infections, particularly with the virulent cagA gene, would be highly prevalent in Navajo adults compared to other non-AI populations, and that diets high in salt, processed meats, and low in vegetables would be associated with prevalent H. pylori infection. Study recruitment occurred from January to October 2021 in two geographic areas of the Navajo Nation. Participants were recruited using online and offline platforms, including social media (Facebook, Instagram), study website (www.theabidstudy.com), newspapers, flyers, word of mouth, and community outreach events. Eligible, consenting study participants provided a stool sample, which was analyzed by droplet digital PCR assays for H. pylori 16S gene detection and cagA virulence gene typing. Participants also provided health and food information through two questionnaires.Preliminary data indicate that prevalence of H. pylori is high in the included regions of the Navajo Nation. The H. pylori prevalence (51.5%, 95% CI: 38.9-64.0) in this study is higher than the prevalence in the US population (35%). Moreover, the cagA virulence gene prevalence in the Navajo with H. pylori was 55.9% (95% CI: 37.9-72.8), which is comparable to the US prevalence of 50%. These early results point to a need of developing prevention strategies to reduce H. pylori infection in the Navajo Nation. Citation Format: Dornell Pete, Amanda I. Phipps, Nina R. Salama, Johanna W. Lampe, Michael C. Wu. The ABID (Assessing the gut microbiota and Individual Diet) Study in the Navajo Nation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5863.

Previous cross-sectional studies have identified a possible link between Helicobacter pylori (H. pylori) infection and dementia. However, the association of H. pylori infection with longitudinal cognitive decline has rarely been investigated. This cohort study aims to demonstrate the effects of H. pylori infection on longitudinal cognitive decline. This cohort study recruited 268 subjects with memory complaints. Among these subjects, 72 had a history of H. pylori infection, and the rest 196 subjects had no H. pylori infection. These subjects were followed up for 24 months and received cognitive assessment in fixed intervals of 12 months. At baseline, H. pylori infected, and uninfected participants had no difference in MMSE scores. At 2 years of follow-up, H. pylori infected participants had lower MMSE scores than uninfected participants. H. pylori infection was associated with an increased risk of longitudinal cognitive decline, as defined by a decrease of MMSE of 3 points or more during follow-up, adjusting for age, sex, education, APOEɛ4 genotype, hypertension, diabetes, hyperlipidemia, and smoking history (HR: 2.701; 95% CI: 1.392 to 5.242). H. pylori infection was associated with larger cognitive decline during follow-up, adjusting for the above covariates (standardized coefficient: 0.282, p < 0.001). Furthermore, H. pylori infected subjects had significantly higher speed of cognitive decline than uninfected subjects during follow-up, adjusting for the above covariates. H. pylori infection increases the risk of longitudinal cognitive decline in older subjects with memory complaints. This study is helpful for further understanding the association between infection and dementia.

We aimed to explore the correlation between P27 expression and Helicobacter pylori (H. pylori) infection in gastric cancer, so as to provide evidence for understanding the pathogenesis of gastric cancer caused by H. pylori infection. A total of 82 samples of gastric cancer tissues and 56 samples of tumor-adjacent normal tissues collected from the gastrectomy were enrolled in this study. Then, 14C-urease breathing test was carried out to evaluate the infection of H. pylori in gastric cancer tissues, the expression of P27 in the tissue samples was detected by the immunohistochemistry staining, and the correlation between the H. pylori infection and P27 expression in gastric cancer was analyzed. Of 82 gastric cancer patients, there were 53 patients with H. pylori infection (64.63%). Among the patients with highly or moderately differentiated gastric cancer, the expression of P27 was much higher than that of patients with poorly differentiated gastric cancer (p < 0.01). Besides, comparison of the P27 expression between males and females, among different age groups, tumor sizes, TNM stages, tumor infiltration degrees, or lymph node metastasis, showed no significant differences (p > 0.05). Analysis of the correlation revealed that P27 expression was negatively correlated with the infection of H. pylori (p < 0.01). Multifactorial logistics regression analysis indicated that tumor differentiation was a risk factor of P27-positive expression in gastric cancer tissues (p < 0.01). In addition, P27 expression in the gastric cancer tissues was lower than that in the tumor-adjacent normal tissues (p < 0.01). In gastric cancer patients, expression of P27 is correlated with H. pylori infection which, via downregulating P27, can cause the cancerization of gastric mucosa, and P27, for its role in the development and progression of gastric cancer, is a potential auxiliary indicator for clinical diagnosis whether gastric cancer is complicated with H. pylori infection. So, P27 is a key indicator for diagnosis, treatment, and prognostic evaluation of disease in the advanced stage.

Background: Helicobacter pylori (H. pylori) infection is considered as a carcinogen for gastric mucosa. The mechanism by which H. pylori are involved in gastric carcinogenesis is still unclear. Objectives: The current study aimed to investigate the effects of H. pylori infection on immunohistochemical expression of p53 and Ki-67 genes in gastric specimens of patients with intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC). Methods: In the study, 42 cases with IM, 38 with DYS and 42 with GC were selected from pathology archive of Ali-ebne-Abitaleb hospital, Zahedan, Iran; p53 and Ki-67 immunohistochemical study was done, accordingly. Kruskal-Wallis and Mann-Whitney U tests were used to compare the groups. Level of significance was set at P < 0.05. Results: In IM specimens, expression of p53 and Ki-67 was significantly higher in the cases with H. pylori infection than those not infected with H. pylori. In DYS specimens, in the group with H. pylori infection, the expression of p53 was significantly higher while expression of Ki-67 was significantly lower than the group without H. pylori infection. In GC specimens, the expression of p53 was significantly higher in the group with H. pylori infection compared to the group without H. pylori infection. Expression of Ki-67 in the specimens with H. pylori infection was not significantly different from those without H. pylori infection. Conclusions: The study results showed that p53 expression increased in IM, DYS and GC cases with H. pylori infection compared to those without H. pylori infection. The results also suggested that, Ki-67 expression was different in precancerous stages of gastric carcinogenesis, based on the infection with H. pylori.

p27kip1 Deficiency Confers Susceptibility to Gastric Carcinogenesis in Helicobacter pylori–Infected Mice

Simple SummaryRisk prediction models incorporate various established risk factors to estimate individual risk specifically in cancer. These models additionally include biological or genetic risk factors to assess cancer risk more accurately. The polygenic risk score (PRS) combines the effects of multiple single-nucleotide polymorphisms (SNPs) that are associated with disease; its discrimination ability was assessed both alone and when used in combination with conventional risk prediction models. As few studies have evaluated the combination of genetic variants to identify high risk population of gastric cancer (GC), and we examined the performance of a GC risk assessment model in combination with SNPs as a PRS in consideration of Helicobacter pylori (H. pylori) infection status. Such a combination improves the identification of a GC-susceptible population among people with H. pylori infection.We investigated the performance of a gastric cancer (GC) risk assessment model in combination with single-nucleotide polymorphisms (SNPs) as a polygenic risk score (PRS) in consideration of Helicobacter pylori (H. pylori) infection status. Six SNPs identified from genome-wide association studies and a marginal association with GC in the study population were included in the PRS. Discrimination of the GC risk assessment model, PRS, and the combination of the two (PRS-GCS) were examined regarding incremental risk and the area under the receiver operating characteristic curve (AUC), with grouping according to H. pylori infection status. The GC risk assessment model score showed an association with GC, irrespective of H. pylori infection. Conversely, the PRS exhibited an association only for those with H. pylori infection. The PRS did not discriminate GC in those without H. pylori infection, whereas the GC risk assessment model showed a modest discrimination. Among individuals with H. pylori infection, discrimination by the GC risk assessment model and the PRS were comparable, with the PRS-GCS combination resulting in an increase in the AUC of 3%. In addition, the PRS-GCS classified more patients and fewer controls at the highest score quintile in those with H. pylori infection. Overall, the PRS-GCS improved the identification of a GC-susceptible population of people with H. pylori infection. In those without H. pylori infection, the GC risk assessment model was better at identifying the high-risk group.

Helicobacter pylori infection in children: recommendations for diagnosis and treatment.

A Functional Polymorphism of Toll-Like Receptor 4 Gene Increases Risk of Gastric Carcinoma and Its Precursors

Regulation of Gastric Carcinogenesis by InflammatoryCytokines.

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 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.

Objective(s):KRAS proto-oncogene mutation can be considered a diagnostic factor for treating various malignancies. Helicobacter pylori infection, a risk factor for stomach cancer, may cause DNA damage and genetic changes. The aim of the current study was to assess the association of gastric cancer and KRAS mutation, demographic factors, and H. pylori infection.Materials and Methods:DNA was extracted from a total of 140 FFPE gastric cancer tissue samples. detection of KRAS mutation (codons 12 and 13) in tumors was performed by PCR amplification, followed by gel electrophoresis and DNA sequencing. PCR diagnosed any H. pylori infection.Results:KRAS mutation was detected in 6 of the 140 (4.2%) gastric cancer tissue samples. 18 samples (12.8%), all of which were male (P<0.05), tested positive for H. pylori infection. KRAS mutations were present in 22.2% (4/18) of the samples with H. pylori infection (P<0.05). The mean age of patients was 62.25±12.61 years (range: 30–93 years). A male predominance (2.5 to 1) was reported in the gastric cancers, and at diagnosis, women were significantly younger than men (P=0.004). No association was observed between age or gender and KRAS mutation. Neither was one found between age and H. pylori infection. Tumors from H. pylori+ subjects were significantly more likely to have KRAS mutation than tumors from H. pylori- subjects (OR=17.1).Conclusion:The data suggest that H. pylori infection when compared with the absence of H. pylori infection, is associated with a higher prevalence of KRAS mutation in gastric cancer.

Variants in Autophagy Genes Affect Susceptibility to Both Crohn's Disease and Helicobacter pylori Infection