BRCA1 is a tumor suppressor gene that plays an important role in transcription, DNA repair, and recombination. In conjunction with other elements involved in tumor suppression, signal transduction, and DNA repair, BRCA1 has a critical function towards maintaining genomic stability. Mutations in BRCA1 is implicated in different types of cancers including familial breast cancer, proliferative breast disease, ovarian cancer, peritoneal papillary serous carcinoma, and prostate cancer. It accounts for approximately 40% of inherited breast cancers and 80% of inherited breast and ovarian cancers.
Rouba et al. (2000) investigated the extent of allelic imbalance at the BRCA1 region in Arabic women with breast cancer. They conducted DNA analysis in 13 cases and analyzed microsatellite markers D17S1323, D17S1325 and D17S855 intragenic to BRCA1. Microsatellite analyses showed 12 of 13 (92%) cases with loss of heterozygosity or microsatellite instability or both. This observation led Rouba and colleagues to the conclusion that the proportion of aberrant findings of the BRCA1 locus in breast cancer appears to be higher in Arabic women than in other populations.
El-Harith et al. (2002) identified unclassified BRCA1 variant Phe486Leu, Asn550His, and five BRCA1 polymorphisms in a cohort of 29 Arab and 11 Asian women.
El-Harith et al. (2002) detected BRCA1 mutation Arg841Trp in an Arab patient from Egypt.
Bar-Sade et al., (1997) examined 639 unrelated healthy male and female Jews of Iraqi extraction and identified three individuals as c.185delAG mutation carriers; thus, a carrier rate of 0.47%. Haplotype analysis of the Iraqi mutation carriers showed that two of the Iraqis shared a haplotype in common with six Ashkenazi mutation carriers, and a third had a haplotype that differed by a single marker. This suggested to Bar-Sade et al. (1997) that the BRCA1 c.185delAG mutation may have arisen before the dispersion of the Jewish people in the Diaspora, at least at the time of Christ. Later, Bar-Saade et al. (1998) examined 43 unrelated women from Iraq for breast or ovarian cancer. They identified one patient with ovarian cancer as carrier for the 185delAG mutation in the BRCA1 gene.
Atoum and Al-Kayed (2004) screened exons 2, 11, and 20 of the BRCA1 gene in 135 Jordanian breast cancer females. Of the studied patients 50 had a family history of breast cancer, 28 had a family history of cancer other than breast cancer, and 57 had no family history of any cancer. Five germline mutations were detected among breast cancer females with a family history of breast cancers (one in exon 2 and 4 mutations in exon 11). Another germline mutation (within exon 11) was detected among breast cancer females with family history of cancer other than breast cancer, and no mutation was detected among breast cancer females with no family history of any cancer or among normal control females.
Amirrad et al. (2005) studied the expression of BRCA1 gene in Kuwait and compared it with the disease prognostic factors such as histological type and grade of breast cancer, C-erbB-2 expression, estrogen (ER) and progesterone (PR) receptor status, and age. BRCA1 gene expression was examined in 48 random samples of paraffin-embedded breast cancer tissues from Mubarak Al-Kabeer Hospital, while BRCA1 protein expression was investigated through Immunohistochemical method by employing antibodies on different epitopes on BRCA1 protein. Furthermore, BRCA1 mRNA expression was identified by using reverse transcription-polymerase chain reaction on 29 Kuwaitis (out of 48 patients). Amirrad et al. (2005) noticed that there was no obvious BRCA1 mRNA and protein expression in 79 and 83% of the breast cancer tissues, respectively. Additionally, negative expression of BRCA1 mRNA and/or protein was found to be associated with over expression of C-erbB-2, high histological grade and the lack of ER and PR receptor status in breast cancer tissues. This study shows that in Kuwait, the majority of breast cancers have negative BRCA1 gene expression and an opposite correlation among BRCA1 gene expression and the parameters that demonstrate poor prognosis in breast cancer.
Bar-Saade et al. (1998) examined 17 unrelated women from Morocco for breast or ovarian cancer. They identified one patient with ovarian cancer as carrier for the c.185delAG mutation in the BRCA1 gene. Bar-Saade et al. (1998) extended their analysis over DNA samples of 354 Jews of Moroccan origin, previously studied for Factor XI deficiency. They screened this group for the presence of the BRCA1 mutation c.185delAG in the germline and detected it in four individuals (1.1%).
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.
Bar-Saade et al. (1998) examined three unrelated Syrian women tested for breast or ovarian cancer. They identified one patient with breast cancer as carrier for the 185delAG mutation in the BRCA1 gene. Haplotype analysis in the patient revealed a unique pattern not observed in other studied patients.
Mestiri et al. (2000) screened Tunisian women with familial or sporadic breast cancer for BRCA1 gene mutations using the Protein Truncation Test and DNA sequencing. A nonsense mutation was found in exon 11 of BRCA1 gene in a single case of familial breast cancer. DNA sequencing did not reveal any mutations in the other exons. The BRCA1 1294del40 mutation was found only in a patient with non familial breast cancer. The 185delAG mutation was absent in all cases of breast cancer. Mestiri and colleagues suggested that the germline mutation of BRCA1 is implicated in breast cancer in Tunisia and that the 185delAG mutation is absent in Arab Tunisian women.
Charef-Hamza et al. (2005) studied the role of BRCA1 in sporadic breast cancer among Tunisian women. Tumors from 21 patients undergoing surgery for breast cancer were examined and none of them had a family history of the disease. The subjects were screened with a panel of three polymorphic microsatellite markers (D17S1322, D17S1323, and EDH-17B) within the BRCA1 region to identify patients for loss of heterozygosity (LOH) BRCA1 status. Microsatellite DNA analysis identified 13 of the 21 informative tumors displaying allelic loss in at least one marker, and yielding a relatively high frequency (61.9%) of LOH at the BRCA1 loci. Charef-Hamza et al. (2005) indicated that the high frequency of LOH at BRCA1 might reflect tumor aggressiveness among Tunisian women. The highest frequency of LOH (58.8%) was observed at D17S1322, whereas the frequency of allelic loss was lower for the other two markers: 35% at D17S1323, and 20% at EDH-17B. The study indicated that at least two target regions in the vicinity of BRCA1 were involved in LOH suggesting deletions of all or part of the gene. There was no significant association between LOH in BRCA1 loci and tumor grade, therefore Charef-Hamza et al. (2005) concluded that deletions in the BRCA1 gene probably occurred early in sporadic mammary carcinogenesis among Tunisians.
Denic and Al-Gazali (2002) examined the consequences of the long-term practice of consanguineous marriage on the prevalence of lethal cancer genes. Denic and Al-Gazali 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, or six times faster than in a non-consanguineous population.
Bar-Saade et al. (1998) examined nine unrelated women from Yemen for breast or ovarian cancer. They identified two patients with ovarian cancers as carriers for the c.185delAG mutation in the BRCA1 gene. Haplotype analysis in one of the two patients revealed a unique pattern not available in other patients analyzed. Furthermore, Bar-Saade et al. (1998) extended their analysis over DNA samples of 200 Jews of Yemenite origin, previously studied for Factor XI deficiency, to screen for the presence of the BRCA1 mutation c.185delAG in the germline. The mutation was not found in any of the Yemenite patient group.
Lerer et al. (1998) described 8765delAG BRCA2 mutation in breast/ovarian cancer patients from three unrelated Jewish families of Yemenite origin.
[See also: BRCA2 gene > Arab, Yemen].