El-Harith et al. (2002) identified the unclassified BRCA1 variant Phe486Leu combined with Asn550His, and the unclassified BRCA2 variant Asp1420Tyr, 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. However, Denic et al. (2003) indicated that no single Arab woman with breast cancer was proven to be due to BRCA1 or BRCA2 mutation. They also suggested that the native population of the Gulf countries have one of the lowest incidences of breast cancer in the world.
Women diagnosed with the BRCA2 mutation develop breast and ovarian cancer with a lifelong likelihood of up to 85%. The presence of a mutation in BRCA2 increases the risk for mutations to occur in other genes. That is why it is believed that the product of this gene act as a repressor. BRCA2 has a low homology to BRCA1, but share similar functions (i.e. DNA repair). Furthermore, BRCA2 gene is located on a different chromosome and mutations in it also increase the risk for ovarian cancer.
El-Harith et al. (2002) identified the unclassified BRCA1 variant Phe486Leu combined with Asn550His, and the unclassified BRCA2 variant Asp1420Tyr, 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. However, Denic et al. (2003) indicated that no single Arab woman with breast caner was proven to be due to BRCA1 or BRCA2 mutation. They also suggested that the native population of the Gulf countries have one of the lowest incidences of breast cancer in the world.
El-Harith et al. (2002) uncovered one novel BRCA2 truncating mutation, the frame-shift mutation 2482delGACT, in a 68 year-old Arab patient of Palestinian descent, who is mother of 7 children and breast fed each of them for 2 years. This mutation is a 4-nucleotide deletion that creates a stop signal at codon 770 of the BRCA2 transcript.
El-Harith et al. (2002) concluded 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.
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 simulated, by computer, the mating of non-consanguineous and consanguineous populations over 40 generations. Denic and Al-Gazali proposed that in a randomly mating population, the BRCA1/2 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, or six times faster than in a non-consanguineous population. The mechanism that better explains this result is that consanguineous couples see more of their homozygous offspring die before reaching reproductive age than do non-consanguineous couples. This is because humans homozygous for breast cancer mutations lack conserved tumor suppressor genes that perform essential cell functions and, thus, are expected to be biologically not viable (Denic and Gazali, 2002).
Lerer et al. (1998) examined three Jewish families of Yemenite origin during the screening for breast or ovarian cancers. Patients of the three unrelated families were diagnosed as having a deletion of 2bp (AG), one of the three (AG)s, starting at position 8761 of the BRCA2 mutation. Lerer et al. (1998) further analyzed nine breast cancer patients of Yemenite origin and without family history of breast or ovarian cancers for the 8765delAG BRCA2 gene mutation. None was found to be a carrier. However, in a sample of 140 healthy individuals of Yemenite origin, one carrier was identified; thus, carrier rate of 0.71%. Lerer et al. (1998) concluded that the 8765delAG BRCA2 gene alteration is a founder mutation in Yemenite Jews, but is not the only one since they identified one individual as carrier of the 5382insC mutation in BRCA1 [See also: Breast Cancer Gene 1 > Epidemiology in the Arab World > Yemen].