Mutational Screening of the BRCA1 Gene in Sporadic Breast Cancer in Kazakhstan Population

PURPOSE Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations. METHODS We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient. RESULTS Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months). CONCLUSION Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.

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Mutation screening of the BRCA1 gene in sporadic breast cancer in southern Chinese populations

The Breast ◽

10.1016/j.breast.2008.08.003 ◽

2008 ◽

Vol 17 (6) ◽

pp. 563-567 ◽

Cited By ~ 4

Author(s):

Zhang Haitian ◽

Lu Yunfei ◽

Zeng Jian ◽

Lin Jian ◽

Liao Qinghua ◽

...

Keyword(s):

Breast Cancer ◽

Sporadic Breast Cancer ◽

Mutation Screening ◽

Brca1 Gene ◽

Chinese Populations ◽

Southern Chinese

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Somatic mutations in the BRCA1 gene in Chinese women with sporadic breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-011-1887-2 ◽

2011 ◽

Vol 132 (1) ◽

pp. 335-340 ◽

Cited By ~ 7

Author(s):

Min Zhang ◽

Ye Xu ◽

Tao Ouyang ◽

Jinfeng Li ◽

Tianfeng Wang ◽

...

Keyword(s):

Breast Cancer ◽

Somatic Mutations ◽

Sporadic Breast Cancer ◽

Chinese Women ◽

Brca1 Gene

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Mutation screening of the BRCA1 gene in sporadic breast cancer in the Central of Iran

Meta Gene ◽

10.1016/j.mgene.2018.04.005 ◽

2018 ◽

Vol 17 ◽

pp. 23-27

Author(s):

Mandana Behbahani ◽

Mokhtar Nosrati ◽

Hassan Mohabatkar

Keyword(s):

Breast Cancer ◽

Sporadic Breast Cancer ◽

Mutation Screening ◽

Brca1 Gene

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Epigenetic silencing of BRCA1 gene associated with demographic and pathologic factors in sporadic breast cancer

European Journal of Cancer Prevention ◽

10.1097/cej.0b013e32834761a6 ◽

2011 ◽

Vol 20 (6) ◽

pp. 478-483 ◽

Cited By ~ 10

Author(s):

Alok Kumar Singh ◽

Anjita Pandey ◽

Mallika Tewari ◽

Hari Shankar Shukla ◽

Hausila Prasad Pandey

Keyword(s):

Breast Cancer ◽

Sporadic Breast Cancer ◽

Brca1 Gene ◽

Epigenetic Silencing

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Allele Imbalance, or Loss of Heterozygosity, in Normal Breast Epithelium of Sporadic Breast Cancer Cases and BRCA1 Gene Mutation Carriers Is Increased Compared With Reduction Mammoplasty Tissues

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.1451 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8613-8619 ◽

Cited By ~ 30

Author(s):

Pamela S. Larson ◽

Benjamin L. Schlechter ◽

Antonio de las Morenas ◽

Judy E. Garber ◽

L. Adrienne Cupples ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Risk ◽

Gene Mutation ◽

Loss Of Heterozygosity ◽

Sporadic Breast Cancer ◽

Brca1 Gene ◽

Reduction Mammoplasty ◽

Breast Epithelium ◽

Brca1 Gene Mutation ◽

Allele Imbalance

Purpose Normal-appearing breast epithelium can contain genetic abnormalities, including allele imbalance (AI), also referred to as loss of heterozygosity. Whether abnormalities are associated with cancer or cancer risk is unknown. Patients and Methods We performed a miniallelotype, using 20 microsatellites, on each of 460 histologically normal, microdissected breast terminal ducto-lobular units (TDLUs) from three groups of women: sporadic breast cancer patients (SP; n = 18), BRCA1 gene mutation carriers (BRCA1; n = 16), and controls undergoing reduction mammoplasty (RM; n = 18). We analyzed the results using Fisher's exact tests, logistic regression, and generalized estimating equations. Results AI was increased three-fold in SP and BRCA1 groups compared with RM. Both the number of TDLUs with AI increased (eight [5%] of 162 in the RM group compared with 24 [15%] of 162 in the SP and 22 [16%] of 136 in the BRCA1 groups; P = .0150), and the proportion of patients with AI increased (five [28%] of 18 in the RM group compared with 15 [83%] of 18 in the SP and 13 [81%] of 16 in the BRCA1 groups; P = .0007). The adjusted odds ratios (OR) for AI in TDLU increased in SP (OR = 15.5) and BRCA1 (OR = 13.7) patients compared with RM (P = .0025). This result was particularly evident on chromosome 17q (P = .0393), where more AI was seen in BRCA1 (OR = 12.4) than in SP (OR = 4.9) patients or RM controls. Conclusion Increased prevalence of AI in normal-appearing epithelium is associated with breast cancer and increased breast cancer risk. The increased prevalence may reflect dysregulation, even in normal-appearing epithelium, of genomic processes contributing to cancer development. The clinical significance of genetic alterations in the subset of controls remains to be determined.

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A somatic mutation in the 5′UTR of BRCA1 gene in sporadic breast cancer causes down-modulation of translation efficiency

Oncogene ◽

10.1038/sj.onc.1204620 ◽

2001 ◽

Vol 20 (33) ◽

pp. 4596-4600 ◽

Cited By ~ 55

Author(s):

Emanuela Signori ◽

Claudia Bagni ◽

Sara Papa ◽

Beatrice Primerano ◽

Monica Rinaldi ◽

...

Keyword(s):

Breast Cancer ◽

Somatic Mutation ◽

Sporadic Breast Cancer ◽

Brca1 Gene ◽

Translation Efficiency

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BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2014.15.11.4513 ◽

2014 ◽

Vol 15 (11) ◽

pp. 4513-4518 ◽

Cited By ~ 4

Author(s):

Yu-Wen Cao ◽

Xin-Ge Fu ◽

Guo-Xing Wan ◽

Shi-Ying Yu ◽

Xiao-Bin Cui ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Sporadic Breast Cancer ◽

Brca1 Gene ◽

Exon 11 ◽

Northwest Region ◽

Gene Exon

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BRCA1 Gene Expression is Down Regulated in Both Familial and Sporadic Breast Cancer Cases in Baghdad- Iraq

Iraqi Journal of Science ◽

10.24996/ijs.2020.61.1.4 ◽

2020 ◽

pp. 34-41

Author(s):

Chemia Adil Ali ◽

Fadhel M. Lafta ◽

Maha Mhammed Al Sayyid ◽

Abdul-Ameer N. Ghaloub Al-Rekabi

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Gene Expression Analysis ◽

Sporadic Breast Cancer ◽

Brca1 Gene ◽

Breast Cancer Patients ◽

Brca1 Expression ◽

Related Mortality

Breast cancer is the commonest cancer and the leading cause of malignancies-related mortality in women worldwide. Understanding the underlying biology of the disease could improve patients’ stratification and may offer novel therapeutic targets and strategies. This study was set to investigate the association between BRCA1 gene expression and some of the clinical features of breast cancer patients in Baghdad-Iraq. Eighty peripheral blood samples were collected from sixty patients diagnosed with breast cancer and twenty healthy age-matched controls for BRCA1 qPCR gene expression analysis. The results showed a significant reduction in BRCA1 gene expression in all of the breast cancer patients with the vast majority of them (75%) having BRCA1expression below 25%. The down regulation of BRCA1 expression also showed consistency in breast cancer patients of both sporadic (n=45) and family history (n=15) cases,with expression averages of 18% and 20.19%, respectively. Moreover, the redcuation in BRCA1 expression was negatively associated with the disease’s grades,asbreast cancer patients with the advanced stage III (n=19) showed the lowest expression average of BRCA1 (13.8%) as compared to those in stages II (n=29) and I (n=12) of the disease (17.7% and 19.8%, respectively). Overall, the study highlights the key role of BRCA1gene expression in the development of breast cancer and suggests its potential utility in the diagnosis strategies and preventing the progression of the disease, especially the sporadic type.

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