Prevalence of BRAF and KRAS Mutations in Colorectal Cancer: A Systematic Review and Meta-Analysis in selected Arab Countries
Colorectal cancer, KRAS mutations, BRAF mutations, Arab populations, Molecular profiling, Targeted therapy, Systematic review, Meta-analysis.
AuthorsAbstractAim The high frequency of colorectal cancer (CRC) in Arab countries indicates many people die from cancer as a result of the CRC. Both KRAS and BRAF mutations are significant factors in the acquisition of CRC, and their impact on CRC tumorigenesis and resistance to therapeutics is systemic. The aim of this research was to provide information about the frequency of KRAS and BRAF mutations in CRC patients in Arab countries (predominantly Egypt, Iraq, Saudi Arabia, and Morocco), and provide insight into the region's future molecular profile of CRC patients and how to manage treatment. Methods After following PRISMA guidelines, we completed a systematic review and meta-analysis. We searched in PubMed, Google Scholar, and ScienceDirect for studies published from 2016 until 2024 that provided KRAS and/or BRAF mutation rates for CRC patients in Arab countries. To estimate the pooled prevalence, we utilized a random effects model. Additionally, we conducted subgroup analyses based on country, detection methods, and year of publication to explore heterogeneity in our analyses. All analyses were conducted using R version 4.4.1. Results A total of 42 studies provided data for 7270 CRC patients for the KRAS analysis and 3361 CRC patients for the BRAF analysis. The KRAS mutations' pooled prevalence rate was found to be 48.1% (95% CI: 42.7% to 53.6%). This high prevalence primarily occurred in codons 12 and 13 of exon 2. On the other hand, the pooled prevalence rate of BRAF mutations was initially 5.08% (95% CI: 2.53% to 9.93%), but after adjusting for significant publication bias using the trim-and-fill method, the true estimated prevalence increased to 8.5% (95% CI: 4.8% to 14.7%). The most common variant seen was V600E . In addition to identifying high prevalence for KRAS mutations, the lower prevalence of BRAF mutation was also found to be clinically significant. Additionally, the current study was characterized by significant heterogeneity related to geographic and methodological differences across included studies. In Conclusion, This meta-analysis demonstrated that the represented Arab countries (with data heavily skewed toward Egypt, Iraq, Saudi Arabia, and Morocco) have a high prevalence of KRAS mutations and lower but still clinically relevant rate of BRAF mutations among patients with colorectal cancer. Additionally, the results demonstrate the necessity for routine molecular profiling to optimize the use of targeted therapies in Arab countries. Future studies must have broader geographic coverage and be conducted using standardized methods to enable successful implementation of precision oncology into the region's healthcare systems.
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