BRCA1 and BRCA2 Mutations in Ethnic Lebanese Arab Women With High Hereditary Risk Breast Cancer (original) (raw)
Related papers
BRCA1 and BRCA2 Mutations in Ethnic Lebanese Arab Women With High Hereditary Risk Breast Cancer
The oncologist, 2015
Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before age 50 years. Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patien...
Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon
Hereditary Cancer in Clinical Practice, 2012
Breast cancer is the most prevalent malignancy in women in Western countries, currently accounting for one third of all female cancers. Familial aggregation is thought to account for 5-10 % of all BC cases, and germline mutations in BRCA1 and BRCA2 account for less of the half of these inherited cases. In Lebanon, breast cancer represents the principal death-causing malignancy among women, with 50 % of the cases diagnosed before the age of 50 years. In order to study BRCA1/2 mutation spectra in the Lebanese population, 72 unrelated patients with a reported family history of breast and/or ovarian cancers or with an early onset breast cancer were tested. Fluorescent direct sequencing of the entire coding region and intronic sequences flanking each exon was performed. A total of 38 BRCA1 and 40 BRCA2 sequence variants were found. Seventeen of them were novel. Seven confirmed deleterious mutations were identified in 9 subjects providing a frequency of mutations of 12.5 %. Fifteen variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases. In conclusion, this study represents the first evaluation of the deleterious and unclassified genetic variants in the BRCA1/2 genes found in a Lebanese population with a relatively high risk of breast cancer.
Mutation analysis of the breast cancer gene BRCA1 among breast cancer Jordanian females
Saudi medical journal, 2004
To screen mutations of the tumor suppressor breast cancer susceptibility gene 1 (BRCA1) within 3 exons among Jordanian breast cancer females. A total of 135 Jordanian breast cancer females were genetically analyzed by denaturing gradient electrophoresis (DGGE) for mutation detection in 3 BRCA1 exons (2, 11 and 20) between 2000-2002 in Al-Basheer Hospital, Amman, Jordan. 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. Screening mutations within exon 2, ex...
Molecular Biology Reports, 2012
Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon-intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described:
BMC Cancer
Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA ...
Breast cancer is the most common cancer in women and its impact on morbidity and mortality is significant and well documented. BRCA genes mutation account for most of the cases of familial breast cancer. Female BRCA1 mutation carriers have an 80% to 85% risk of developing breast cancer over their life-time. This study aims to detect 5382insC ,185delAG and C61G mutations in BRCA1 gene in healthy females and breast cancer female patients in Qalubia Governorate and correlate them with the presence or absence of family history of breast &/ or ovarian cancer to allow identification of individuals at high risk. Materials and methods: 50 females divided into 20 healthy females and 30 breast cancer patients with or without family history of breast &/or ovarian cancers were included in the study.185delAG and 5382insC mutation were detected by multiplex mutagenically separated PCR (MS -PCR) and C61G mutation was detected using the RFLP method. Results: It was found that the incidence of BRCA1 gene mutation in the breast cancer group was higher than its incidence in the control group Also the incidence of BRCA1 gene mutation in the groups with family history was higher than in the groups without family history. In addition, multiple exons mutation frequency was higher than one exon mutation in the breast cancer group with family history .Moreover, 5382insC mutation was found to be the most frequent BRCA 1 gene mutation among the females of Qalubia governorate followed by C61G mutation and 185 delAG mutation. Conclusion: In conclusion, BRCA1 gene mutation and multiple BRCA1 exons mutations play an important role in the pathogenesis of familial breast cancer in Qalubia Governorate, Egypt.
Meta Gene, 2018
Background: The three founder mutations of BRCA1/2 (185delAG, 5382insC and 6174delT) have been reported to be associated with breast cancer. This work was designed to check for the frequency of these genetic mutations in Egyptian women affected with breast cancer compared to healthy first-degree relatives and unrelated controls. Subjects and methods: This work is a case control study including 43 women diagnosed with breast cancer. Their genetic data were compared to controls including 63 first degree relatives in addition to 91 healthy unrelated controls from the same locality. DNA deletion or insertion mutations were characterized in blood samples of all participants using the PCR technique. Results: The frequency of BRCA1 (185delAG) mutation in BC patients and their first-degree relatives was higher than healthy controls (2.3% and 3.2% vs. 1.1%). However, the other two mutations BRCA1 (5382insC) and BRCA2 (6174delT) showed higher frequencies among healthy controls than BC patients and their first-degree relatives (49.5% vs. 11.6% and 6.3%; 61.5% vs. 11.6% and 14.3%, respectively). Furthermore, BC patients with BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations showed no significant difference compared to others regarding their clinical and laboratory markers. Conclusions: This study indicates that BRCA1 (185delAG) mutation might contribute to the incidence of breast cancer among Egyptian women, but not with BRCA1 (5382insC) and BRCA2 (6174delT) mutations. Furthermore, there was no significant association between these three founder mutations and the clinical presentation of BC among Egyptian women.
BRCA1 and BRCA2 Mutations are they Related to Breast Cancer in a Sample of Tunisian Population?
Cancer Therapy & Oncology International Journal, 2015
Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. This work aimed to identify mutations in BRCA1 and BRCA2 genes to explore the existence of population-specific recurrent or founder mutations, in Tunisian breast cancer families. We have screened for germline mutations in seventeen Tunisian high-risk breast cancer patients using direct sequencing. Index patients, diagnosed before age 45, possessing a positive family history or bilateral breast cancer were asked for detailed information on family history of breast or any other cancer type in their families. One family out of 17 (6%) carried BRCA 1 mutations and no BRCA2 mutations was found. One recurrent mutation in BRCA 1 was identified, c.798-799delTT, which appear to represent founder mutation in this population. Thirty-one variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases.
BMC Cancer
Background Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. Because the contribution of BRCA1/2 germline mutations to BC in the Northeastern population of Morocco remains largely unknown, we conducted this first study to evaluate the prevalence and the phenotypic spectrum of two BRCA1/2 pathogenic mutations (the founder BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA). This choice was also argued by the presence of an apparent specific geographical connection of these mutations and the Northeastern region of Morocco. Methods Screening for the germline mutations c.5309G>T and BRCA2 c.1310_1313delAAGA was performed by sequencing on a total of 184 breast cancer (BC) patients originated from the Northeastern region of Morocco. The likelihood of identifying a BRCA mutation is calculated using the Eisinger scoring model. The clinical and pathologic features were compared between the BRCA-positive and...
Clinical Genetics, 2007
Background: To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods: Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results: Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion: Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.