Background: Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk. Methods: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia. Results: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). Conclusion: KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Increased plasma total homocysteine (tHcy) levels have been shown to be a risk factor for coronary artery disease (CAD). The common methylenetetrahydrofolate reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation was associated with increased risk of CAD and plasma levels of tHcy. We also evaluated interactions between this polymorphism, mild elevated tHcy levels and conventional risk factors of CAD. Method. Using PCR-RFLP analysis, we studied the frequency of the C677T genotypes and its effect on CAD and on tHcy concentrations in 400 subjects without and with CAD angiographically confirmed. There were 210 subjects with CAD and 190 subjects without CAD. Results. The frequencies of the C677T genotypes were 53 (59.5 in controls versus 48.1 in cases), 34.8 (32.1 in controls versus 37.1 in cases), and 11.8 (8.4 in controls versus 14.8 in cases), respectively, for 677CC, 677CT, and 677TT. The genotype frequencies were significantly different between case and control groups (P.05). The 677T allele enhances the risk of CAD associated to HHcy (P.01). In multivariate analysis models, MTHFR C677T polymorphism effect on CAD was masked by other risk factors. HHcy was only and independently influenced by MTHFR polymorphism and smoking habits, and it is a strong predictor of CAD independently of conventional risk factors. Conclusion. Our data suggest that HHcy is strongly and independently associated to CAD risk increase; and MTHFR C677T polymorphism and smoking habits were the main predictors of tHcy levels. The CAD risk increase is mainly associated with mild HHcy in 677TT, whereas in 677CT and 677CC it is mainly associated with the conventional risk factors.

Human Papillomavirus (HPV) infection is a significant global health concern linked to various cancers, particularly cervical cancer. Timely and accurate detection of HPV is crucial for effective management and prevention strategies. Traditional laboratory-based HPV testing methods often suffer from limitations such as long turnaround times, restricted accessibility, and the need for trained personnel, especially in resource-limited settings. Consequently, there is a growing demand for point-of-care (POC) HPV testing solutions that offer rapid, easy-to-use, and convenient screening at the primary care level. This review provides a comprehensive overview of recent advancements and emerging technologies utilized in POC HPV testing using isothermal amplification methods, in addition to evaluating their diagnostic performance, sensitivity, specificity, and clinical utility compared to conventional laboratory-based assays, particularly in low-resource settings, where access to centralized laboratory facilities is limited. We provide insights into the potential of isothermal nucleic acid amplification to revolutionize cervical cancer screening and prevention efforts worldwide, with emphasis on the need for continued research, innovation, and collaboration to optimize the performance, accessibility, and affordability of POC HPV testing solutions, ultimately contributing to the worldwide effort towards the elimination of this disease.

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF^V600E tumors compared to PTC-BRAF^wt tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves’ disease, ten goiters, and 20 hyperplasias). We detected the BRAF^V600E mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAF^V600E expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAF^V600E mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations.

Circulating tumor DNA (ctDNA) profiling offers non-invasive insights for personalized prostate cancer management. This systematic review provides the first comprehensive appraisal of ctDNA assay methods, genomic targets, and their clinical correlations and proposes practical recommendations to guide future standardization and validation. We searched PubMed, ScienceDirect, Scopus, and the Cochrane Library starting December 2024 following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. From 229 records, 44 studies (10,631 patients) met the inclusion criteria. Plasma ctDNA analyzed by NGS predominantly profiled TP53 (72.7%), AR (70.4%), BRCA1/2 (61.3%), ATM (50%), RB1 (47.7%), and PTEN (41%). ctDNA positivity and specific key alterations correlated with poorer overall and progression-free survival. BRCA1/2-mutant patients benefited from Olaparib plus Abiraterone, while persistent alterations predicted early progression. Beyond synthesizing existing evidence, we identify key gaps, such as inconsistent reporting of variant allele fractions, limited diversity in study populations, and underexplored rare alterations. We recommend unified reporting standards (e.g., variant allele frequency thresholds and panel composition) and prioritized prospective trials to validate high-impact targets. These steps will accelerate the integration of ctDNA into routine precision oncology practice worldwide.

Pathogenic variants (PVs) in BRCA genes have been mainly associated with an increasing risk of triple negative breast cancer (TNBC). The contribution of PVs in non-BRCA genes to TNBC seems likely since the processing of homologous recombination repair of double-strand DNA breaks involves several genes. Here, we investigate the susceptibility of genetic variation of the BRCA and non-BRCA genes in 30 early-onset Moroccan women with TNBC.