Aspects épidémiologiques et cliniques de l’infection à Helicobacter pylori à travers une étude marocaine

Introduction : Helicobacter pylori est responsable de multiples pathologies gastroduodénales telles que la gastrite, l’ulcère et l’adénocarcinome gastrique. Dans les pays en voie de développement, l’infection à H.pylori constitue un problème de santé publique. Le but de cette étude marocaine est de déterminer la prévalence de l’infection à H.pylori et d’étudier l’impact des différents facteurs épidémiologiques ainsi que les principales maladies gastriques associées à cette infection. Patients et méthodes : Les renseignements cliniques et sociodémographiques ont été recueillis à partir de 837 dossiers de patients archivés (1998-2011) à l’Institut Pasteur du Maroc et dans un centre médical de gastroentérologie à Casablanca. Tous les patients avaient bénéficié d’une fibroscopie et le diagnostic a été fait par un examen histologique. Résultats : 837 patients ont été compulsés (âge moyen: 44 ±12,4 ans). La prévalence de l’infection à H.pylori est de 69,2 %. Ce taux semble après une analyse statistique, lié significativement à l’âge. En effet, l’infection est plus importante (80,2 %) dans le groupe d’âge 31-40 ans. Par contre le sexe ne présente aucun effet sur la prévalence de l’infection qui est surtout associée aux gastrites chroniques (91,8 %). De plus, 35,5 % de patients souffrant de cette pathologie appartenaient à la même tranche d’âge 31-40 ans. Conclusion : Il est à noter que dans notre étude, le groupe d’âge 31 à 40 ans présentait la plus forte prévalence de H. pylori et le taux le plus élevé de gastrites. Il constituerait ainsi un terrain à risque pour la survenue d’un cancer gastrique.Introduction: Helicobacter pylori is the main cause of most gastroduodenal diseases as gastritis, peptic ulcer, and gastric adenocarcinoma. In developing countries, it appears as a major public health concern. The goals of this Moroccan study were to assess the prevalence of Helicobacter pylori infection, epidemiological factors and gastroduodenal diseases associated with this infection. Patients and methods: Clinical and sociodemographic informations (age and sex) were collected from 837 archived patient’s files (1998-2011) found at the Institute Pasteur in Morocco; based at the Health centre of gastroenterology in Casablanca; the diagnosis was based on histology. Results: 837 patients were included (mean age: 44 ± 12.4 years). The prevalence of H. pylori infection was 69.2%. The difference of prevalence between the age group 31 to 40 years (80.2%) and other age groups was statistically significant. Moreover, the gender had no significant correlation. In 91.8%, the infection was associated with chronic gastritis. In addition, 35.5% of patients with chronic gastritis were between 31 and 40 years old. Conclusion: During the study, we noticed that the 31-40 years age group revealed the strongest prevalence of H. pylori and the most well brought up rate of gastritis. Besides, those patients are the most exposed to gastric cancers

Molecular docking of a set of flavonoid compounds with Helicobacter pylori virulence factors CagA and VacA

Introduction: Cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (VacA) proteins are the main Helicobacter pylori virulence factors. These toxins are associated with severe gastric diseases. Flavonoids are plant secondary metabolites that have shown great antibacterial effects. This work aimed to study the interaction of a set of flavonoid compounds with CagA and VacA proteins using molecular docking. Methods: A set of 54 flavonoid compounds were used in this study, and 36 of which passed the Lipinski rules of 5. The 3D structures of CagA and VacA proteins were obtained from the Protein Data Bank. The molecular docking was performed using AutoDock Vina software and the results were expressed in terms of binding energies (kcal/mol). Protein-ligand interactions were analyzed using PyMOL software. Results: For the CagA protein, the licochalcone A molecule showed the highest binding affinity (-8 kcal/mol). For the VacA protein, the galangin, luteolin, and apigenin molecules showed the highest binding affinity (-8.9, -8.5, and -8.2 kcal/mol, respectively). Interactions of the licochalcone A, galangin, luteolin, and apigenin with CagA and VacA proteins involved their hydroxyl groups and/or their carbonyl groups. Conclusion: Our study showed that these compounds might have the potential for their development into drugs for controlling H. pylori pathogenicity

Association of Tumor Necrosis Factor Receptor 1 Promoter Gene Polymorphisms (-580 A/G and -609 G/T) and TNFR1 Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to H. pylori Infection in a Moroccan Population

Chronic inflammation due to H. pylori infection is the risk factor of gastric cancer (GC). Through its receptor (TNFR1), TNF-α plays a fundamental role in inflammatory, infectious, and tumor processes. Dysregulation of TNFR1 gene expression could impact many biological processes that can lead to cancer. This study is aimed at evaluating the association of TNFR1 promoter gene polymorphisms (-580 A/G and -609 G/T) and TNFR1 serum levels with GC and precancerous lesion susceptibility. Patients suffering from gastric lesions (65 chronic gastritis, 50 precancerous lesions, and 40 GC) related to H. pylori infection and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNFR1 gene promoter sequencing, and TNFR1 serum levels were measured by the ELISA quantitative method. Concerning TNFR1 -609 G/T locus, we noticed that the T allele was associated with an attenuated susceptibility to GC (OR=0.4; p value = 0.02). At the genotypic level and under the recessive model, the TNFR1 -609 TT genotype showed a decreased risk of GC (OR=0.3, p value = 0.03) compared to the combined (GG/GT) genotypes. TNFR1 serum levels have been increased together with gastric lesion severity (p value < 0.05). The TNFR1 -609 TT genotype seemed linked to a low level of sTNFR1 compared to GT and GG genotypes (p value = 0.07). Concerning TNFR1 -580 A/G locus, no significant relation was noticed between this polymorphism and GC susceptibility, as well as with the TNFR1 serum level. Our results suggest that the TNFR1 -609 T allele appears to have a protective effect against GC. High levels of TNFR1 serum levels seemed to be associated with the aggressiveness of gastric lesions. Therefore, our results suggest that TNFR1 -609 T/G polymorphism and the TNFR1 serum levels may be related to GC susceptibility

Infections and cancer: the “fifty shades of immunity” hypothesis

Abstract Background Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. Discussion Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways – from functional aspects to evolutionary considerations such as modernity mismatches – by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels. Summary Infectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase our knowledge about immune interactions between infections and cancer

Association des polymorphismes -238(G/A) et -308(G/A) du promoteur du TNF alpha et des taux sériques de TNF alpha avec la susceptibilité aux lésions précancéreuses et cancéreuses gastriques associées à l'infection par Helicobacter pylori dans la population Marocaine.

International audienceObjective: Helicobacter pylori (H. pylori) induces the production of tumor necrosis factor-alpha (TNF-α), which is closely related to a gastric epithelial injury. TNF-α gene polymorphism and TNF-α serum levels are associated with various malignant conditions. Identification of the ideal marker for gastric cancer (GC) is still the leading aim of several trials. Physio-pathological considerations of GC led us to investigate the association of two TNF-α promoter polymorphisms (-308G>A and -238G>A), and TNF-α serum levels with the susceptibility to gastric precancerous (PL) and GC.Methods: Patients suffering from gastric lesions (65 chronic gastritis, 50 PL, 40 GC) related to H. pylori ‎infection , and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNF-α gene promoter sequencing and TNF-α serum levels are measured by ELISA quantitative method.Results: Regarding TNF-α-308 G/A locus, we noticed higher risk for GC (OR=4.3, CI 1.5-11.9, p-value=0.005) and PL (OR=3.4, CI 1.2-9.2, p-value=0.01) for individuals with AA/GA genotypes compared to GG genotype. Concerning TNF-α-238 G/A locus, we noticed higher risk for GC (OR=5.9, CI 1.2-27.5, p-value=0.01) and PL (OR=4.8, CI 1.3-18, p-value=0.01) for individuals with GG genotype compared to AA/GA genotypes. We noticed that TNF-α serum levels have been increased together with gastric lesions severity. Moreover, TNF-α-308 and TNF-α-238 A alleles seemed to, respectively, upregulate and downregulate TNF-α serum levels.Conclusion: The TNF-α -308 A allele has a promotive effect for GC progression, whereas the TNF-α -238 A allele has a protective function against GC progression. High levels of TNF-α seemed to be associated with the aggressiveness of gastric lesions. TNF-α gene polymorphisms and TNF-α serum levels might be helpful to select those patients who are at high risk for GC

Additional file 1: Figure S1. of Infections and cancer: the “fifty shades of immunity” hypothesis

Antagonistic pleiotropy and mismatch concept. Antagonistic pleiotropy describes a situation where particular genes (e.g. inflammatory genes) have opposite effects on fitness at different ages, such that their effects are beneficial in early life, when natural selection is strong (following infections for instance), but harmful at later ages, when selection weakens. Whereas, mismatches between genotype and environment arise when a phenotype or genotype that were selected in a particular context (e.g. in a high parasitic burden) becomes detrimental in a new environment. (PPT 239 kb