Comparative Study of Helicobacter Pylori Resistance to Clarithromycin and Metronidazole and Its Association with Epidemiological Factors in A Moroccan Population.

OBJECTIVE: Knowledge of local antibiotic resistance is crucial to the adaption of the effective empirical first-line treatment for Helicobacter Pylori (H. pylori) infection. This study aimed to evaluate the prevalence of H. pylori resistance to clarithromycin and compare it with that of metronidazole, and highlight the impact of epidemiological factors and gastric lesions severity on H. pylori resistance. METHODS: The susceptibility to clarithromycin of 96 isolates was determined by PCR-RFLP and the susceptibility to metronidazole of 185 isolates was determined by classic PCR. RESULT: Our results showed that the prevalence of H. pylori resistance to clarithromycin ( 14.6%) was low compared to that recorded with metronidazole ( 62.7%). Moreover, we remarked that 7.3% of isolates were co-resistant to both antibiotics. The assessment of epidemiological factors' impact on the resistance to studied antibiotics has revealed no association. Besides, our results had demonstrated that the metronidazole and clarithromycin resistance was not related to the severity of gastric lesions. CONCLUSION: In our population, clarithromycin seems to be an effective antibiotic as long as the resistance rate of H. pylori is low. In contrast to metronidazole, it appears that this antibiotic will lose its efficacy, due to the high rate of resistance among our population. Therefore, each population must conduct their epidemiologic studies separately to survey the resistance profile of strains and choose the appropriate antibiotic, in order to avoid the failure of H. pylori eradication and the development of severe gastric diseases.

Association of Helicobacter pylori vacA polymorphisms with the risk of gastric precancerous lesions in a Moroccan population.

INTRODUCTION: Helicobacter pylori infection is the major risk factor of atrophic gastritis and intestinal metaplasia. The vacA gene is one of the most virulence factors of H. pylori and genetic diversity in its s, m, i, and d regions is associated with gastric lesions severity. This study aimed to investigate the association of vacA s, m, i, and d regions with the risk of atrophic gastritis and intestinal metaplasia in a Casablanca population. METHODOLOGY: A total of 210 patients suffering from gastric lesions (chronic gastritis, atrophic gastritis, and intestinal metaplasia) were enrolled. The type of lesion was diagnosed by histological examination. Detection of H. pylori infection and genotyping of vacA regions were carried out by PCR. RESULTS: The prevalence of H. pylori was 95%. The most common vacA genotypes were s2 (51.5%), m2 (77%), i2 (60.5%), and d2 (58.5%). VacA s1, m1, and i1 genotypes were associated with a high risk of intestinal metaplasia, while the vacA d1 genotype increases the risk of atrophic gastritis and intestinal metaplasia. The most common vacA combination was s2/m2/i2/d2 (52%), and it was more detected in chronic gastritis. The moderate virulent vacA combination (s1/m2/i1/d1) increases the risk of atrophic gastritis, while the most virulent vacA combination (s1/m1/i1/d1) increases the risk of intestinal metaplasia. CONCLUSIONS: Genotyping of vacA d region might be a reliable marker for the identification of vacA virulent strains that represent a high risk of developing precancerous lesions (atrophic gastritis and intestinal metaplasia).

Next-generation sequencing of BRCA1 and BRCA2 genes in Moroccan prostate cancer patients with positive family history.

Prostate cancer is the most common male cancer in Morocco. Although sporadic forms account for a large proportion of patients, familial forms of prostate cancer are observed in 20% of cases and about 5% are due to hereditary transmission. Indeed, germline mutations in BRCA1/2 genes have been associated with prostate cancer risk. However, the spectrum of these mutations was not investigated in Moroccan Prostate cancer patients. Thereby, the aim of this study was to characterize and to estimate the prevalence of germline BRCA1/2 mutations and large rearrangements in Moroccan patients with familial prostate cancer. The entire coding regions and intron/exon boundaries of BRCA1 and BRCA2 genes have been analyzed by next generation sequencing (NGS) in a total of 30 familial prostate cancer patients. Three pathogenic mutations were detected in four unrelated patients (13.3%). One BRCA1 mutation (c.1953_1956delGAAA) and two BRCA2 mutations (c.7234_7235insG and BRCA2ΔE12). In addition, sixty-three distinct polymorphisms and unclassified variants have been found. Early identification of germline BRCA1/2 mutations may be relevant for the management of Moroccan prostate cancer patients.

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.

Associations of the -238(G/A) and -308(G/A) TNF-α Promoter Polymorphisms and TNF-α Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to Helicobacter pylori Infection in a Moroccan Population.

OBJECTIVE: 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.

Infections and cancer: the "fifty shades of immunity" hypothesis.

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. 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.

Dietary risk factors for nasopharyngeal carcinoma in Maghrebian countries.

North Africa is one of the major Nasopharyngeal Carcinoma (NPC) endemic regions. Specific food items unique to this area were implicated to be associated with NPC risk, but results were inconsistent. Here we have performed a large-scale case-control study in the Maghrebian population from Tunisia, Algeria and Morocco. From 2002 to 2005, interviews were conducted on 636 cases and 615 controls. Controls were hospitalized individuals from 15 non-cancer hospital departments, or friends and family members of non-NPC cancer subjects, matched by center, childhood household type (rural or urban), age and sex. Conditional logistic regression is used to evaluate the risk of factors. In results, consumption of rancid butter, rancid sheep fat and preserved meat not spicy (mainly quaddid) were associated with significantly increased risk of NPC, while consumption of cooked vegetables and industrial preserved fish was associated with reduced risk. Other foods such as fresh citrus fruits and spicy preserved meat (mainly osban) in childhood, industrial made olive condiments in adulthood, were marginally associated. In multivariate analyses, only rancid butter, rancid sheep fat and cooked vegetables were significantly associated with NPC. In regard to possible causative substances, our results implicate the involvement of butyric acid, a potential Epstein-Barr virus (EBV) activator.