scholarly journals Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Joaira Bakkach ◽  
Mohamed Mansouri ◽  
Touria Derkaoui ◽  
Ali Loudiyi ◽  
ElMostafa El Fahime ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Brca2 Gene ◽  
Germline Mutations ◽  
Genetic Alterations ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
History Of

Abstract 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.

scholarly journals BRCA1 and BRCA2 Germline Mutations in Malaysian Women with Early-Onset Breast Cancer without a Family History

PLoS ONE ◽  
2008 ◽  
Vol 3 (4) ◽  
pp. e2024 ◽  
Author(s):  
Gaik Theng Toh ◽  
Peter Kang ◽  
Sharlene S. W. Lee ◽  
Daphne Shin-Chi Lee ◽  
Sheau Yee Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Germline Mutations ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2 ◽  
Malaysian Women

scholarly journals Hereditary Susceptibility to Breast Cancer: Significance of Age of Onset in Family History and Contribution of BRCA1 and BRCA2

1999 ◽  
Vol 15 (1-3) ◽  
pp. 89-92 ◽  
Author(s):  
Thomas S. Frank ◽  
Amie M. Deffenbaugh ◽  
Mark Hulick ◽  
Kathryn Gumpper
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Early Onset ◽  
Age Of Onset ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2 ◽  
Degree Relative ◽  
Age Of Diagnosis ◽  
History Of

OBJECTIVE: To correlate mutations in BRCA1 and BRCA2 with family history of breast cancer in a first-degree relative for women diagnosed with breast cancer before age 45 who do not have a personal or family history of ovarian cancer.METHODS: Family history for women with breast cancer diagnosed before age 45 was provided by ordering physicians via a test requisition form designed for this purpose. Gene analysis was performed by dye primer sequencing for the entire coding regions of BRCA1 and BRCA2. Because a personal and family history of ovarian cancer are known to be significantly associated with mutations, women with either were excluded from analysis.RESULTS: Overall, deleterious mutations in BRCA1 or BRCA2 were identified in 85 of 440 women (19%) with breast cancer under 45. Mutations were identified in 73 of 276 women (26%) with a first degree family history of breast cancer compared to 12 of 164 without (7%) (P <.0001). When results were analyzed by the age of diagnosis in first degree relatives, mutations were identified in 56 of 185 women (30%) with at least one first degree relative with breast cancer diagnosed before age 50 compared with 17 of 91 women (19%), where the first degree family history of breast cancer was at or over age 50 (P = .042).CONCLUSION: Among women with breast cancer diagnosed before age 45, a first-degree relative diagnosed with the disease under age 50 is an indicator of a mutation in BRCAl or BRCA2 even in the absence of a family history of ovarian cancer. Therefore, women diagnosed with early-onset breast cancer should be asked about the age of onset in any first-degree relative diagnosed with the disease, as well as about any family history of ovarian cancer. Mutations in BRCA2 account for a substantial proportion of hereditary breast cancer. Therefore, studies that are limited to BRCA1 or that do not analyze by age of onset of breast cancer in relatives may underestimate the contribution of mutations in BRCAl and BRCA2 to women with early onset breast cancer.

scholarly journals Familial Risks, Early-Onset Breast Cancer, and BRCA1 and BRCA2 Germline Mutations

2003 ◽  
Vol 95 (6) ◽  
pp. 448-457 ◽  
Author(s):  
G. S. Dite ◽  
M. A. Jenkins ◽  
M. C. Southey ◽  
J. S. Hocking ◽  
G. G. Giles ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Germline Mutations ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2

scholarly journals Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abdul Khalid Siraj ◽  
Tariq Masoodi ◽  
Rong Bu ◽  
Sandeep Kumar Parvathareddy ◽  
Kaleem Iqbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Middle Eastern ◽  
Mutation Screening ◽  
Univariate Analysis ◽  
Positive Family History ◽  
Germline Mutations ◽  
Pathogenic Mutations ◽  
History Of

Abstract Background The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited. Methods We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing. Results Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS. Conclusions TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.

scholarly journals A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

BMC Cancer ◽  
2008 ◽  
Vol 8 (1) ◽  
Author(s):  
Geertruida H de Bock ◽  
Catharina E Jacobi ◽  
Caroline Seynaeve ◽  
Elly MM Krol-Warmerdam ◽  
Jannet Blom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Population Based ◽  
Early Onset Breast Cancer ◽  
History Of

scholarly journals Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22226-e22226
Author(s):  
A. Kwong ◽  
L. Wong ◽  
C. Wong ◽  
F. Law ◽  
E. Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
History Of ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

e22226 Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women. No significant financial relationships to disclose.

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