Low Frequency of Pathogenic Variants in BRCA1 Exons 11/20 and BRCA2 Exon 11 Suggests Divergent Mutational Hotspots in Sudanese Breast Cancer Patients: A Case-Control Study.

BACKGROUND

Breast cancers represent a heterogeneous group of diseases; approximately 7% may be attributed to inherited pathogenic variants in BRCA1 and BRCA2, with exon 11 of BRCA1 representing the most frequently mutated region globally.

OBJECTIVES

This study aimed to investigate the frequency and nature of sequence variants in BRCA1 exons 11 and 20 and BRCA2 exon 11 in a Sudanese cohort, and to determine whether these established mutational hotspots harbor recurrent pathogenic variants in this underrepresented population.

DESIGN

This was a case-control study conducted at Shendi's Tumor Treatment and Cancer Research Center in Northern Sudan.

METHODS

The study included fifty-two female breast cancer patients and thirty healthy female controls aged at least 18 years. Demographic data and blood samples were collected for genomic DNA extraction. Polymerase Chain Reaction (PCR) and Sanger sequencing were performed for BRCA1 (exons 11 and 20) and BRCA2 (exon 11). Variants were classified using ACMG/AMP criteria and analyzed using bioinformatics tools and SPSS.

RESULTS

Invasive ductal carcinoma was the predominant histological type, significantly associated with grade II tumors (P = 0.0001). Non-hereditary breast cancers were more prevalent (55.8%), with second-degree relatives most commonly affected in hereditary cases (69.6%). Three BRCA1 sequence variants were identified, all classified as benign or likely benign. These variants were found at comparable frequencies in cases (13/52, 25.0%) and controls (8/30, 26.7%; P = 0.863). Variant presence was significantly associated with Jaalia ethnicity (P = 0.047) and observed exclusively in IDC cases, though these associations did not reach statistical significance for tumor characteristics.

CONCLUSION

No pathogenic variants were identified in BRCA1 exons 11 and 20 or BRCA2 exon 11 in this Sudanese cohort. Given that BRCA1 exon 11 constitutes approximately 60% of the coding sequence and harbors the majority of pathogenic variants in other African populations, these findings suggest that mutational hotspots may differ in this population. Expanded genomic studies encompassing complete coding regions are warranted.