scholarly journals Prevalence and Spectrum of Breast Cancer Inherited Mutations in Uganda and Cameroon Women

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 43s-43s
Author(s):  
B. Adedokun ◽  
Y. Zheng ◽  
P. Ndom ◽  
A. Gakwaya ◽  
T. Makumbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Positive Family History ◽  
Pathogenic Mutation ◽  
Germline Mutations ◽  
Sub Saharan Africa ◽  
Age At Diagnosis ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Sub Saharan

Background: Breast cancer among indigenous Africans is characterized by higher prevalence of triple-negative disease and poor prognosis. A previous study in Nigeria reported a strikingly high prevalence of deleterious germline mutations in BRCA1 and BRCA2 among Nigerian women with breast cancer. It is unknown if this is true in other sub-Saharan African countries. Aim: The objective of this study is to determine the frequency of germline mutations among an unselected sample of women in Africa. Methods: We conducted a case-control study of breast cancer in Uganda and Cameroon to investigate genetic and nongenetic risk factors for breast cancer. Breast cancer cases were enrolled in two tertiary hospitals in the two countries, unselected for age at diagnosis and family history. Controls who were free of breast cancer were enrolled in the same hospitals and matched to cases on age. A 24-gene sequencing panel was used to test germline mutations in cases and controls. Results: There were 176 cases and 177 controls with a mean age at diagnosis of 46.2 years for cases and mean age at interview of 46.7 years for controls. Among cases, 18.2% carried a pathogenic mutation in a breast cancer gene: 6.3% in BRCA1, 6.3% in BRCA2, 1.7% in ATM, 1.1% in PALB2, 0.6% in BARD1, 0.6% in CDH1, 0.6% in TP53, and 1.2% in any of 17 other genes. Among controls, 2.3% carried a pathogenic mutation in one of the 24 susceptibility genes. Cases were 9.6-fold more likely to carry a mutation compared with controls (odds ratio=9.61, 95% confidence interval: 3.28-38.1; P < 0.001). The mean age of breast cancer cases with pathogenic BRCA1 mutations was 38.3 years compared with 46.7 years among other cases without such mutations ( P = 0.03). There was a trend that cases with a positive family history had higher chance of carrying a mutation (33.3%) than cases without (17.1%), but few cases reported a positive family history. Conclusion: Our findings confirm the earlier report of a high proportion of deleterious mutations in BRCA1 and BRCA2 among breast cancer patients in sub-Saharan Africa. As most of these women present with advanced breast cancer, there is an urgent need to improve access to genomic testing and life saving cancer medicines including chemotherapy and clinical trials of novel agents like PARP inhibitors. Given the high burden of inherited breast cancer, genetic risk assessment should be integrated into cancer control plans in sub-Saharan Africa.

scholarly journals Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history

2005 ◽  
Vol 123 (4) ◽  
pp. 192-197 ◽  
Author(s):  
Rozany Mucha Dufloth ◽  
Sílvia Carvalho ◽  
Juliana Karina Heinrich ◽  
Júlia Yoriko Shinzato ◽  
César Cabello dos Santos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Positive Family History ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
Brca2 Mutations ◽  
Exon 11 ◽  
Brca1 And Brca2 Mutations

CONTEXT AND OBJECTIVE: BRCA1 and BRCA2 are the two principal hereditary breast cancer susceptibility genes, and the prevalence of their mutations among Brazilian women is unknown. The objective was to detect BRCA1 and BRCA2 mutations in Brazilian patients with breast cancer, so as to establish genetic profiles. DESIGN AND SETTING: Cross-sectional study, in Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Brazil, and Institute of Pathology and Molecular Immunology, University of Porto, Portugal. METHODS: Thirty-one breast cancer patients with positive family history (criteria from the Breast Cancer Linkage Consortium) were studied, and genomic DNA was extracted from peripheral blood. Single-strand conformation polymorphism was used for the analysis of exons 2, 3, 5, and 20 of BRCA1. Cases showing PCR products with abnormal bands were sequenced. Exon 11 of BRCA1 and exons 10 and 11 of BRCA2 were directly sequenced in both directions. RESULTS: Four mutations were detected: one in BRCA1 and three in BRCA2. The BRCA1 mutation is a frameshift located at codon 1756 of exon 20: 5382 ins C. Two BRCA2 mutations were nonsense mutations located at exon 11: S2219X and the other was an unclassified variant located at exon 11: C1290Y. CONCLUSION: The BRCA1 or BRCA2 mutation prevalence found among women with breast cancer and such family history was 13% (4/31). Larger studies are needed to establish the significance of BRCA mutations among Brazilian women and the prevalence of specific mutations.

scholarly journals Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Samuel Terkper Ahuno ◽  
Anna-Lisa Doebley ◽  
Thomas U. Ahearn ◽  
Joel Yarney ◽  
Nicholas Titiloye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Grade ◽  
Circulating Tumor Dna ◽  
Sub Saharan Africa ◽  
Health Study ◽  
Breast Cancer Patients ◽  
Cancer Driver ◽  
Sequencing Studies ◽  
Sub Saharan ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients.

Breast-conservation therapy in early-stage breast cancer patients with a positive family history

2002 ◽  
Vol 9 (9) ◽  
pp. 912-919 ◽  
Author(s):  
Georges Vlastos ◽  
Nadeem Q. Mirza ◽  
Funda Meric ◽  
Kelly K. Hunt ◽  
Attiqa N. Mirza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Early Stage ◽  
Positive Family History ◽  
Breast Conservation ◽  
Breast Conservation Therapy ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients

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.

DNA repair germline pathogenic mutation associations with treatment duration and family history in prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 245-245
Author(s):  
James Vu ◽  
Marcus Marie Moses ◽  
Lahiru Ranasinghe ◽  
Patrick Cotogno ◽  
Charlotte Manogue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Family History ◽  
Treatment Outcomes ◽  
Treatment Duration ◽  
Pathogenic Mutation ◽  
Germline Mutations ◽  
Cancer Type ◽  
History Of

245 Background: Germline mutation testing for metastatic prostate cancer patients creates a potential opportunity to personalize targeted therapies to improve treatment outcomes. The goal of this study was to characterize cancer family history, and evaluate treatment outcomes, in mCRPC patients with DNA repair pathogenic germline alterations. Methods: A retrospective study of metastatic PCa patients at Tulane Cancer Center identified 246 patients undergoing germline testing using panels (30-80 genes) (Color.com or Inviate.com). Clinical annotations included family history, life-extending treatments, and treatment duration. Statistical analyses including chi-square and Wilcoxon Rank Sum. Results: In the 246 patients tested for germline mutations, 27 patients (11.0%) had ≥1 DNA repair germline pathogenic mutation (BRCA2 = 11, BRCA1 = 3, CHEK2 = 5, ATM = 3, NBN = 1, PMS2 = 2, MSH2 = 1, PALB2 = 1) while 219 patients (89.0%) possessed no pathogenic mutation in these genes. Patients with a DNA repair pathogenic mutation were more likely to have > 2 family members affected by cancer, regardless of cancer type or degree of relationship (p = 0.04). In the DNA repair population, 5 pathogenic patients had no family history of cancer (18.5%, n = 5). Patients were more likely to have a germline alteration if they had 1 or more first degree relatives affected with breast cancer (p = 0.00001). Median lines of life-extending treatments to date between the pathogenic and non-pathogenic population were equal at 2. There were no significant differences in treatment duration for abiraterone (p = 0.49), enzalutamide (p = 0.99), docetaxel (p = 0.28), cabazitaxel (p = 0.53), carboplatin+docetaxel (p = 0.41), or radium-223 (p = 0.59) between the two groups. Conclusions: In this study, DNA repair pathogenic germline mutations did not affect treatment durations or lines of therapy but these studies are underpowered. The relationship between a family history of breast cancer and a DNA repair pathogenic mutation has not previously been reported.

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

Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history

2014 ◽  
Vol 144 (3) ◽  
pp. 635-642 ◽  
Author(s):  
Peter Choon Eng Kang ◽  
Sze Yee Phuah ◽  
Kavitta Sivanandan ◽  
In Nee Kang ◽  
Eswary Thirthagiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Mutation Testing ◽  
Recurrent Mutation ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
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 Risk models for breast cancer

2019 ◽  
Vol 15 (4) ◽  
pp. 503-510
Author(s):  
T. V. Pyatchanina ◽  
A. N. Ohorodnyk
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Scientific Evidence ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Risk Models ◽  
Brca1 And Brca2 Genes

Scientific evidence indicates the stabilization of indicators of morbidity and mortality from breast cancer in women in Ukraine and the existence of a number of models for predicting the breast cancer risk with the consideration of life style factors, detectable mutations of BRCA1 and BRCA2 genes, family history, as well as predicative and prognostic factors (clinical, molecular-biological) to determine the possible ways of the tumor process and the survival of breast cancer patients.

scholarly journals BREAST CANCER;

2014 ◽  
Vol 21 (06) ◽  
pp. 1128-1132
Author(s):  
Abeer Nisar ◽  
M Naim Siddiqi ◽  
Naveed ur Rehman ◽  
Raza ur Rahman
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Family History ◽  
Menopausal Status ◽  
Positive Family History ◽  
American Woman ◽  
Breast Cancer Patients ◽  
Civil Hospital ◽  
Early Menarche ◽  
History Of

Objective: To assess the risk factors for breast cancer in patients attending oncology OPD of civil hospital Karachi, Pakistan. Introduction: Breast cancer is the single largest cause of death among women1,2. The probability of American woman developing breast cancer in their life is 7 in 11. Studies from subcontinent show that the incidence of breast cancer is increasing, with an estimated 80,000 new cases diagnosed annually. Breast cancer is the second most common type of cancer after lung cancer in Pakistan and ranked first in women. Only 10% women are diagnosed, out of them, 75% women do not get treatment and die within 5 years6. Data from Pakistan about the risk factors or association is not only scanty but also does not comment on the use of fatty diet in breast cancer patients. Method: A cross-sectional descriptive study conducted at Oncology OPD of civil hospital Karachi (CHK) from October 2009 -April 2011. One Hundred and Fifty consecutive patients having histopathalogical diagnosis of breast cancer were assessed for different risk factors that included marital status, parity, age, menopausal status, family history of breast cancer, prolong use of oral contraceptives, breast feeding, , early menarche, trauma to the breast and fatty diet. Result: Mean age of patients was 48 years. Three fourth (73%) of these female were above the age of 40 years. Consumption of fatty diet was found in 62.67% while positive family history of breast cancer was present in 34% of the cases. Early menarche and being nulliparous were not as strong risk factors as in previous studies. Conclusions: Our study has highlighted the need of further exploration in this area that would not only help this population but also enhance our understanding of different risk factors. This will have important implications for the overall management of breast cancer.

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