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Microsatellite Instability (MSI-H vs MSS) and Mismatch Repair Gene Alterations in Hospital-Based Studies of Colorectal Cancer in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

DOI: 10.4236/ajmb.2026.164023, PP. 324-358

Keywords: Colorectal Cancer, Mismatch Repair Deficiency, Microsatellite Instability, Survival Analysis, Pooled Hospital-Based Proportion, Sub-Saharan Africa

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Abstract:

Background: The rising incidence of colorectal cancer (CRC), driven by an ageing population and ongoing epidemiological transition, underscores the need for improved surveillance strategies. In sub-Saharan Africa (SSA), however, limited access to molecular diagnostics and fragmented genomic data hinder the characterization of mismatch repair deficiency (MMRd). These constraints contribute to delayed detection, with most cases diagnosed at advanced stages, thereby compromising prognosis and the effective delivery of oncologic care. Objectives: This study aimed to estimate the pooled hospital-based proportion of CRC across SSA, characterize the molecular architecture of mismatch repair genes (MLH1, MSH2, MSH6, PMS2), stratify tumor aggressiveness according to microsatellite instability (MSI/MSS) status, and evaluate overall survival following diagnosis. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO(CRD420261341249). A comprehensive search was conducted across six databases (PubMed, Scopus, Embase, ScienceDirect, Google Scholar, and HINARI) to identify studies published between 2009 and 2025 in 18 SSA countries. Egger’s test was performed using Stata 17; Kaplan-Meier survival curves were generated using Python3.13. Results: A total of 47 studies were included from 1074 identified records. The findings revealed a CRC profile distinct from that observed in Western populations. The mean age at diagnosis was 52.52 years (95% CI: 49.68 - 55.36), with a pooled hospital-based proportion of 44.48% (95% CI: 28.89 - 60.65) reflecting in-hospital recruitment patterns within the sub-Saharan African context. Recurrent alterations were observed in MSH6 (54/126) and MLH1 (14/18). MSI-H colorectal tumors frequently exceeded 40%, suggesting substantial Lynch syndrome contribution and immunotherapy responsiveness potential; the pooled MSI-H proportion in sub-Saharan Africa was 25.71% (95% CI: 16.32 - 36.34) (I2 = 92.10%; p < 0.001). Despite a lower reported pooled hospital-based proportion of colorectal cancer compared with Western regions, outcomes remain poor, with a 5-year overall survival of 31.13% (95% CI: 22.10 - 40.93). Conclusion: The pooled proportion of MSI-H in colorectal cancer in sub-Saharan Africa was characterized by high inter-study heterogeneity and poor 5-year survival, emphasizing the urgent need to improve molecular diagnostic capacity to enable personalized and precision oncology.

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