KRAS mutation and its association with clinicopathological features of colorectal cancer patients in Africa: a systematic review and meta-analysis

Abstract Background Mutations in the KRAS gene serve as significant oncogenic drivers in colorectal cancer (CRC), greatly affecting therapy response and prognosis. While the prevalence and clinical significance of KRAS mutations have been extensively documented in Western populations, information from African contexts remains limited and inconsistent. Therefore, this study aimed to determine the pooled frequency of KRAS gene mutations and their relationship with the clinicopathological features of CRC patients in Africa. Methods A comprehensive systematic search was conducted across databases, including PubMed/MEDLINE, Embase, Scopus, Hinari, African Journals Online (AJOL), and African Index Medicus (AIM), as well as search engines and websites to identify studies reporting KRAS mutations in CRC patients throughout Africa. A random-effect meta-analysis was applied to estimate the pooled frequencies. Subgroup analysis and meta-regression were performed to identify possible sources of heterogeneity. A leave-one-out sensitivity analysis was also conducted to assess the robustness of the findings. Associations with clinical features were summarized descriptively due to the limited availability of effect size estimates. Results A total of 40 studies involving 5045 CRC patients were included. The overall pooled frequency of KRAS mutations was 39% (95% CI: 34%–44%), with substantial heterogeneity across studies (I² = 96.9%, p < 0.001). The mutation at exon 2 was the most prevalent, representing a pooled estimate of 37% (95% CI: 31%–43%) among all CRC patients. Within Exon 2, Codon 12 was the most common, with Gly12Asp at 12% (95% CI: 9%-14%) and Gly12Val at 9% (95% CI: 7%-10%) substitutions. Subgroup analysis revealed a higher mutation prevalence in North Africa (41%, 95% CI: 36%–45%). Sensitivity analyses confirmed the robustness of the results, and meta-regression showed no significant influence of publication year or sample size. Evidence of publication bias was not detected. Although quantitative pooling was limited, some studies suggested that KRAS mutations were associated with younger age, right-sided tumor location, lymph node involvement, and adverse pathological features, including lymphovascular invasion, perineural invasion, and distant metastasis. Conclusion KRAS mutations were prevalent among CRC patients in Africa, with predominant exon 2 and codon 12 alterations. The findings underscore the need to expand molecular testing across African oncology centers and signify the importance of KRAS profiling to guide targeted therapies.