Objective: The aim of this pilot study was to screen the major segments of the BRCA1 and BRCA2 genes for disease-associated mutations in Arab and Asian women with breast cancer from the Kingdom of Saudi Arabia.
Methods: Deoxyribonucleic acid samples from 29 Arab women and 11 Asian women, with unilateral breast cancer were investigated for BRCA1 and BRCA2 mutations. For this purpose single strand conformation polymorphism and direct nucleotide sequencing techniques were employed. This study was carried out at King Fahad Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia, during the time frame March 2000 through to August 2001.
Results: One novel BRCA2 truncating mutation, the frame-shift mutation 2482delGACT, was uncovered in an Arab patient of Palestinian descent. This mutation is a 4-nucleotide deletion that creates a stop signal at codon 770 of the BRCA2 transcript. The BRCA1 disease-associated mutation Arg841Trp was detected in another Arab patient from Egypt. The clinical presentation in the 2 heterozygous carriers of these 2 mutations is described here. In addition the unclassified BRCA1 variant Phe486Leu combined with Asn550His, and the unclassified BRCA2 variant Asp1420Tyr, were identified in Arab patients. Five BRCA1 polymorphisms and 6 BRCA2 polymorphisms were detected at different allele frequencies in both mutation carriers and patients with normal genotype.
Conclusion: We conclude that BRCA1 and BRCA2 mutations are likely to contribute to the pathogenesis of familial breast cancer in female patients from the Kingdom of Saudi Arabia.