Landscape of therapeutically actionable HRR gene variants in Moroccan breast and ovarian cancer: A systematic review and meta-analysis.

Abstract

e15075 Background: Hereditary breast and ovarian cancers (HBOC) in Morocco remain underexplored, despite a steady increase in access to germline genetic testing over the past decade. While BRCA1 and BRCA2 are well-established drivers of hereditary risk, the contribution of other homologous recombination repair (HRR) genes is increasingly recognized, particularly in the era of targeted therapies such as PARP inhibitors. A comprehensive synthesis of available data is therefore needed to clarify the prevalence, distribution, and clinical relevance of HRR gene variants in the Moroccan population. Methods: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. PubMed, Cochrane, and Scopus databases were searched for studies reporting germline HRR gene variants in Moroccan patients with breast and/or ovarian cancer. Eligible studies were assessed for methodological quality using the Newcastle–Ottawa Scale. Variant prevalence estimates were pooled across cohorts using meta-analytic models, with heterogeneity evaluated to ensure robustness of the findings. Results: Thirteen studies met the inclusion criteria, encompassing 762 patients screened for BRCA1, 641 for BRCA2, and 110 for additional HRR genes. The pooled prevalence of pathogenic or likely pathogenic variants was 9.3% (95% CI: 5.8–12.8%) for BRCA1 and 10.0% (95% CI: 8.3–11.6%) for BRCA2, yielding a combined BRCA1/2 prevalence of 14.7% (95% CI: 12.0–17.4%). Inclusion of the broader HRR gene spectrum increased the overall prevalence to 19.7%, highlighting a substantial proportion of patients harboring non-BRCA actionable variants. Recurrent alterations, including BRCA1:c.5309G > T, BRCA1:c.3279delC, and BRCA2:c.1310_1313delAAGA, were repeatedly observed across independent cohorts, supporting the hypothesis of founder or population-enriched mutations. Conclusions: Approximately one in five Moroccan patients fulfilling HBOC testing criteria carries a pathogenic HRR variant with potential diagnostic and therapeutic relevance. The identification of recurrent and population-enriched mutations provides a strong evidence base for optimizing genetic testing strategies in the Moroccan population. These findings support the design of population-adapted HRR gene panels, informed by local mutational spectra, with the aim of improving risk assessment, genetic counseling, and the implementation of precision oncology in resource-constrained settings.