scholarly journals INHERITED MUTATION IN BRCA1 AND BRCA2 IN BREAST CANCER

2019 ◽  
Vol 3 (10) ◽  
Author(s):  
Diksha Mishra ◽  
Savita Kumari ◽  
Navneeta R. Kumar
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Breast Cancer Susceptibility ◽  
Brca1 And Brca2 ◽  
Suppressive Function ◽  
Cancer Susceptibility Genes ◽  
Increased Risk ◽  
Tumor Suppressive Function ◽  
Damaged Dna

BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks. If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer. Keywords: BRCA1; BRCA2; Breast cancer; Mutation; Gene.

scholarly journals Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

2007 ◽  
Vol 14 (4) ◽  
pp. 330-337 ◽  
Author(s):  
Dawn C. Allain ◽  
Kevin Sweet ◽  
Doreen M. Agnese
Keyword(s):  
Medical Management ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

scholarly journals Clinical Implications of the Breast Cancer Susceptibility Genes BRCA1 and BRCA2

2005 ◽  
Vol 1 (1) ◽  
pp. 27-34
Author(s):  
Steven A Narod
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Cancer Chemoprevention ◽  
Breast Cancer Susceptibility ◽  
High Risk Population ◽  
Clinical Genetics ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes

Genetic testing for BRCA1 and BRCA2 mutations has become an important part of the practice of medical oncology and clinical genetics over the past decade. Increasing numbers of women are requesting a genetic test so that they may better understand their personal risks of breast and ovarian cancer, and so that they may take appropriate measures to reduce the risk. Several of the risk factors can be modified, including breastfeeding and the use of oral contraceptives. A significant number of women opt for preventive mastectomy or oophorectomy, which will dramatically reduce the risks of breast and ovarian cancer. Chemoprevention with tamoxifen is still uncommon, largely due to women's fears of the side effects of the drug. A number of studies have shown that magnetic resonance imaging is superior to conventional mammography in terms of the early detection of breast cancer in the high-risk population. This article explores what is known about assessing genetic risk and the evidence supporting a range of preventive strategies.

scholarly journals 027.Mapping novel breast cancer susceptibility genes by linkage analysis of Australian multiple case kindreds

2004 ◽  
Vol 16 (9) ◽  
pp. 27
Author(s):  
Graham J. Mann ◽  
Gulietta M. Pupo ◽  
Beth Newman ◽  
Deon J. Venter ◽  
John L. Hopper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Age Of Onset ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Loci ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
Major Breast ◽  
Breast Cancer Linkage Consortium ◽  
Brca1 And Brca2 Mutations

We have been using the resources of the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) and of the Australian Breast Cancer Family Study (ABCFS) to identify kindreds suitable for mapping high penetrance breast cancer susceptibility loci other than BRCA1 and BRCA2. A 10 cM genomewide search was carried out in 40 families in which BRCA1 and BRCA2 mutations had been excluded with high probability. The highest LOD score under heterogeneity (HLOD) was 2.16 (non-parametric LOD 1.83, P = 0.04) at the 11p telomere; several other regions with HLODs = 1.5–2.0 also merited investigation using fine mapping but have so far neither been confirmed or rejected by these analyses. Subsets based on age of onset and presence of other cancers correlated to some extent with particular linkage peaks and several regions (notably 2q and 13q) corresponded to areas of suggestive linkage reported recently in more limited studies of other cohorts. A large collaborative analysis of these data together with those from similar studies undertaken by members of the international Breast Cancer Linkage Consortium (BCLC) is under way. It is therefore likely that further major breast cancer susceptibility loci will be localised in the near future. The complementarity of these studies with genetic association, candidate gene and tumour-based approaches will be discussed.

scholarly journals Association between Single-Nucleotide Polymorphisms in Breast Cancer Susceptibility Genes and Clinicopathological Characteristics

2020 ◽  
Author(s):  
Kejing Zhang ◽  
Lili Tang ◽  
Shouman Wang ◽  
Yuan Yang ◽  
Hao Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Susceptibility ◽  
Molecular Subtype ◽  
Breast Cancer Susceptibility ◽  
Clinicopathological Characteristics ◽  
Negative Association ◽  
Nucleotide Polymorphisms ◽  
Cancer Susceptibility Genes ◽  
Increased Risk

Abstract Background: The incidence rate of breast cancer ranks highest in both China and the United States. Understanding the associations between genetic polymorphisms and clinicopathological features of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.The purpose of the present study was to evaluate the associations between seven tagging single nucleotide polymorphisms (tSNPs) and risk of breast cancer assessed by tumor pathological characteristics and body mass index (BMI). Methods: Seven tSNPs of four breast cancer susceptibility genes were analyzed in 734 Chinese women with breast cancer and 672 age-matched healthy controls, then the association with clinicopathological characteristics, BMI, molecular subtype, TNM staging and lymph node status, was determined. Results: Two tSNPs, rs12951053 located in TP53 and rs16945628 in BRIP1, displayed increased risk of breast cancer in the BMI ≧ 25 kg/m2 group (OR=1.50, 95% CI: 1.02-2.21, P=0.041 and OR=1.92, 95% CI: 1.13-3.26, P=0.015, respectively). The other five tSNPs (rs1805812, rs2735385 and rs6999227 in NBS1, rs7220719 in BRIP1 and rs2299941 in PTEN) displayed a decreased risk of breast cancer in the 18.5≤BMI<25 kg/m2 group. Two tSNPs, rs12951053 in TP53 and rs7220719 in BRIP1 exhibited an increased risk of triple‐negative breast cancer(TNBC) (OR=1.50, 95% CI: 1.05-2.15, P=0.026 and OR=2.13, 95% CI: 1.05-4.29, P=0.032, respectively), and the three tSNPs in NBS1 (rs1805812, rs2735385 and rs6999227) all displayed negative association with both luminal B breast cancer and TNBC. The tSNP rs2299941 in PTEN also exhibited a negative association with each breast cancer molecular subtype, except TNBC. The majority of tSNPs displayed a negative association with stage II or III breast cancer. A number of tSNPs showed a negative association with breast cancer that was lymph node negative or with 1-3 positive nodes. Only one tSNP, rs12951053 in TP53 displayed a positive association with lymph node negative breast cancer (OR=1.43, 95% CI: 1.08-1.91, P=0.013). Conclusions: The majority of tSNPs displayed a negative association with breast cancer and only a few tSNPs (rs12951053 in TP53, rs16945628 and rs7220719 in BRIP1) showed an increased risk of breast cancer as defined by clinicopathological characteristics.

scholarly journals Association Between Single-Nucleotide Polymorphisms in Breast Cancer Susceptibility Genes and Clinicopathological Characteristics

2020 ◽  
Author(s):  
Kejing Zhang ◽  
Lili Tang ◽  
Shouman Wang ◽  
Yuan Yang ◽  
Hao Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Susceptibility ◽  
Molecular Subtype ◽  
Breast Cancer Susceptibility ◽  
Clinicopathological Characteristics ◽  
Negative Association ◽  
Nucleotide Polymorphisms ◽  
Cancer Susceptibility Genes ◽  
Increased Risk

Abstract Objective The purpose of the present study was to evaluate the associations between seven tagging single nucleotide polymorphisms (tSNPs) and risk of breast cancer assessed by tumor pathological characteristics and body mass index (BMI). Methods Seven tSNPs of four breast cancer susceptibility genes were analyzed in 734 Chinese women with breast cancer and 672 age-matched healthy controls, then the association with clinicopathological characteristics, BMI, molecular subtype, TNM staging and lymph node status, was determined. Results Two tSNPs, rs12951053 located in TP53 and rs16945628 in BRIP1, displayed increased risk of breast cancer in the BMI ≧ 25 kg/m2 group (OR = 1.50, 95% CI: 1.02–2.21, P = 0.041 and OR = 1.92, 95% CI: 1.13–3.26, P = 0.015, respectively). The other five tSNPs (rs1805812, rs2735385 and rs6999227 in NBS1, rs7220719 in BRIP1 and rs2299941 in PTEN) displayed a decreased risk of breast cancer in the 18.5 ≤ BMI < 25 kg/m2 group. Two tSNPs, rs12951053 in TP53 and rs7220719 in BRIP1 exhibited an increased risk of triple-negative breast cancer(TNBC) (OR = 1.50, 95% CI: 1.05–2.15, P = 0.026 and OR = 2.13, 95% CI: 1.05–4.29, P = 0.032, respectively), and the three tSNPs in NBS1 (rs1805812, rs2735385 and rs6999227) all displayed negative association with both luminal B breast cancer and TNBC. The tSNP rs2299941 in PTEN also exhibited a negative association with each breast cancer molecular subtype, except TNBC. The majority of tSNPs displayed a negative association with stage II or III breast cancer. A number of tSNPs showed a negative association with breast cancer that was lymph node negative or with 1–3 positive nodes. Only one tSNP, rs12951053 in TP53 displayed a positive association with lymph node negative breast cancer (OR = 1.43, 95% CI: 1.08–1.91, P = 0.013). Conclusions The majority of tSNPs displayed a negative association with breast cancer and only a few tSNPs (rs12951053 in TP53, rs16945628 and rs7220719 in BRIP1) showed an increased risk of breast cancer as defined by clinicopathological characteristics.

BRCAPRO Validation, Sensitivity of Genetic Testing of BRCA1/BRCA2, and Prevalence of Other Breast Cancer Susceptibility Genes

2002 ◽  
Vol 20 (11) ◽  
pp. 2701-2712 ◽  
Author(s):  
Donald A. Berry ◽  
Edwin S. Iversen ◽  
Daniel F. Gudbjartsson ◽  
Elaine H. Hiller ◽  
Judy E. Garber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Susceptibility Genes

PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.

scholarly journals Breast cancer susceptibility genes: Options for those carrying BRCA1 mutations

2002 ◽  
Vol 10 (3) ◽  
pp. 119-122 ◽  
Author(s):  
Mirjana Brankovic-Magic ◽  
Radmila Jankovic ◽  
Sinisa Radulovic
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Risk Reduction ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Breast Cancer Susceptibility ◽  
Prophylactic Surgery ◽  
Prevention Strategies ◽  
Cancer Susceptibility Genes ◽  
Brca Mutation Carriers

The discovery of the association between breast and ovarian cancer and the BRCA genes and the development of methods for genetic testing made it possible to screen women for genetic predisposition to develop hereditary breast cancer (HBC). Parallelly, prevention strategies, including clinical surgical and medical interventions become available in order to reduce cancer risk. In a meantime, we became aware of limitations of genetic testing from the aspect of BRCA gene penetrance, negative result interpretation etc. All of these, together with data that invasive prevention strategies such as prophylactic surgery demonstrate better results in risk reduction than regimens including self and clinical-examination, face BRCA mutation carriers with difficult choice for risk reduction options. Therefore, the patients at high risk of HBC can best make informed decisions when guided by a multidisciplinary genetic counseling team.

scholarly journals Genetic Susceptibility to Breast cancer in East Azerbaijan, Iran

2018 ◽  
Vol 15 (2) ◽  
pp. 469-473
Author(s):  
Mahdiyeh Pashaei ◽  
Jamal Eivazi Ziaei ◽  
Alireza Nikanfar ◽  
Babak Emamalizadeh ◽  
Seyyed Mojtaba Mohaddes Ardebili
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Cancer Susceptibility ◽  
Positive Family History ◽  
Critical Factor ◽  
Breast Cancer Susceptibility ◽  
Genetic Alterations ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
East Azerbaijan

Breast cancer is the most common cause of death among women in the world and in Iran. A number of risk factors for breast cancer development have been identified, among which the most important is positive family history. Alterations in different genes, including BRCA1, BRCA2, p53, CHEK2, PTEN, and ATM, also induce a predisposition for breast cancer. Among these changes, BRCA1 and BRCA2 alterations are the strongest drivers of breast cancer predisposition. This study was aimed at contributing to the development of appropriate methods for detecting genetic alterations, such as single or multiple exon deletions and amplifications, in the aforementioned genes. We used multiplex ligation-dependent probe amplification (MLPA) to determine genetic alterations in 150 female patients who hail from East Azerbaijan, Iran and suffer from familial breast cancer. Specifically, we investigated copy number changes in BRCA1, ATM, p53, CHEK2, and PTEN. MLPA results showed no remarkable mutations in the study population. Size coverage is a critical factor for MLPA to accurately detect potential mutations in familial breast cancer susceptibility genes.

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