BRCA2 is a tumor suppressor gene that plays a critical role in maintaining genomic stability. It is involved in double-strand break repair, homologous recombination, and centrosome duplication. Mutations in BRCA2 gene are associated with Fanconi Anemia, Complementation Group D1 and an increased risk of developing hereditary breast and ovarian cancers. BRCA2 mutations are responsible for about 25% of hereditary breast cancer. They are also associated with other types of cancers, such as prostate, gallbladder, and pancreatic cancers.
A study conducted by El-Harith et al. (2002) in a cohort of 29 Arab and 11 Asian women, identified two BRCA2 heterozygous mutations – novel 2482delGACT and unclassified Asp1420Tyr – in three patients. In addition, six common BRCA2 polymorphisms were detected in both Arab and Asian women at similar allele frequencies.
El-Harith et al. (2002) uncovered a novel BRCA2 truncating mutation (2482delGACT) in a 68 year-old Arab patient of Palestinian descent. This mutation is a 4-nucleotide deletion that creates a stop signal at codon 770 of the BRCA2 transcript.
Ghazwani et al. (2016) carried out a review of Fanconi anemia (FA) patients at a Saudi Arabian hospital. Ten patients from consanguineous families were included in the study and a genetic analysis was carried out to determine underlying mutations. Two patients, a boy aged 2-years and a girl of 6-months, were found to have a homozygous c.7007G>A mutation in the BRCA2 gene. This mutation was not found in 50 Saudi Arabian non-FA controls. Both patients showed a similar phenotype of microcephaly, café au lait spots, hypopigmentation, abnormal ears and a short neck. The boy suffered from testicular embryonal rhabdomyosarcoma and T cell acute lymphoblastic leukemia while the girl had stage 4 neuroblastoma. Both patients also had a strong family history of cancer. The fact that both patients belonged to the same tribe supported the possibility of a founder mutation or hotspot. The study also noted that, compared to European patients, most of the identified mutations were in downstream FA pathway genes, rendering the FANCD2 protein monoubiquitination assay ineffective in diagnosing most Saudi cases of FA.
Denic and Al-Gazali (2002) examined the consequences of the long-term practice of consanguineous marriage on the prevalence of lethal cancer genes. They proposed that in a randomly mating population, the BRCA1/BRCA2 carrier rate decreases on average 0.0035% every 25 years, whereas, in a highly consanguineous population, the carrier rate decreases on average 0.022% every 25 years, six times faster than in a non-consanguineous population.
Lerer et al. (1998) described 8765delAG BRCA2 mutation in breast/ovarian cancer patients from three unrelated Jewish families of Yemenite origin. Lerer et al. (1998) further analyzed 8765delAG BRCA2 gene mutation in three different groups. The first group included nine breast cancer patients of Yemenite origin without a family history of breast or ovarian cancers. None were found to be a carrier. The second group consisted of 140 healthy individuals of Yemenite origin with one carrier identified. The last group studied comprised 41 Jewish breast cancer patients of which there were no carriers supporting the idea that 8765delAG BRCA2 is limited to Yemenite Jews. Lerer et al. (1998) concluded that the 8765delAG BRCA2 gene alteration is a founder mutation in Yemenite Jews.
[See also: Breast Cancer Gene 1 > Arab, Yemen].