RAS/RAF/MAPK Pathway Mutations as Predictive Biomarkers in Middle Eastern Colorectal Cancer: A Systematic Review.

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Colorectal cancer (CRC) is a significant health concern globally.
• Understanding the genetic landscape of CRC, specifically RAS and BRAF mutations, is crucial for effective treatment.
• Geographical variations in mutation prevalence can impact patient outcomes and therapeutic strategies.

Purpose of the Study:

• To investigate the prevalence and spectrum of rat sarcoma (RAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations in colorectal cancer (CRC) patients in the Middle East.
• To explore the association between these mutations, geographical location, and clinicopathological features.
• To provide insights into regional differences in CRC genetic profiles.

Main Methods:

• Systematic literature review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework.
• Comprehensive search of multiple electronic databases including PubMed, Science Direct, Web of Science, Scopus, and Google Scholar.
• Analysis of data from 19 eligible studies encompassing 2960 CRC patients.

Main Results:

• RAS mutation prevalence was 38.1% in the studied Middle Eastern CRC cohort.
• Kirsten RAS Viral Oncogene Homolog (KRAS) mutations were most frequent (37.1%), with G12D being the most common specific mutation.
• Neuroblastoma RAS Viral Oncogene Homolog (NRAS) mutations occurred in 3.3%, and BRAF mutations in 2.6%, with V600E being the most common BRAF alteration.

Conclusions:

• RAS and BRAF mutation patterns in CRC patients show significant ethnic and geographical variations.
• This study highlights a higher prevalence of KRAS mutations in Middle Eastern CRC patients compared to other regions.
• Understanding these regional mutation differences is vital for personalized treatment planning and developing targeted therapies for CRC.