Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa

Abstract

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.

Efficacy of First-line Therapy With Anti-EGFR Versus Anti-VEGF Therapy for WT RAS Metastatic Colorectal Cancer: Real-world Experience from a Single Institute

“…In preliminary pathological gene pro les, only 38 patients (29.5%) had all WT RAS status, and the majority of patients (69, 53.5%) had WT KRAS/NRAS exons 2 and 3. Low prevalence of KRAS or NRAS exon 4 mutation was found in a retrospective cohort study in North Africa (19), however, potential KRAS or NRAS exon 4 mutations were not assessed comprehensively in our database.…”

KRAS, NRAS and BRAF Mutational Profile of Colorectal Cancer in a Series of Moroccan Patients

“…43 Similarly to the present study, in North Africa, G12D and G12 C have been revealed in 31.6 and 10.2%, respectively, of all KRAS mutations in patients with CRC. 44 In addition, the G12D mutation is estimated to impact 180,000 patients in the U.S. and Europe, and occurs in 12% of patients with CRC, with ∼80,000 patients in the U.S. and Europe, 45 while G12 C is estimated to impact >70,000 patients in the U.S. and Europe and occurs in 3%–4% of patients with CRC, with ∼20,000 patients in the U.S. and Europe. 45 , 46 …”

Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis

“…Here, we found that HFeD promoted dysbiosis of the gut bacteria, which led to an increase in SLPI. Mechanically, SLPI released from gut promoted tumorigenesis activated the MAPK signaling pathway, which has been proven to be involved in the pathogenesis 59 , progression 60 and oncogenesis 61 of CRC. Bacterial-derived LPS can activate the MAPK signaling pathway 62 , which is consistent with the abovementioned dysfunction of intestinal barrier, bacterial translocation, and elevated serum LPS.…”