scholarly journals Gene Mutations in Hereditary Breast Cancer- A Review

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Pathima Fairoosa ◽  
Chamindri Witharana
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Gene Mutations ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Germline Gene ◽  
Brca1 And Brca2 ◽  
Repair Gene ◽  
Cancer Susceptibility Genes

The most prevalent form of cancer in females is breast cancer. Roughly 5%-10% of breast cancers are hereditary, and they are associated with Germline gene mutations, inherited from parents. Germline gene mutations increase the risk of developing cancer earlier in life compared to noninherited cases (sporadic cancer). BRCA1 and BRCA2 are well-studied tumour suppressor genes associated with hereditary breast cancer. Even though mutations in BRCA1 and BRCA2 are assumed to responsible the majority of hereditary breast cancers cases, many other breast cancer susceptibility genes have been identified in the last few decades. Identification of many germline mutations was possible due to advance sequencing technologies. Most of these genes are belongs to tumour suppressors and DNA damage repair gene families (DNA double-strand break repair and DNA mismatch repair). These genes play a vital role in genomic stability and cell cycle control suggesting that any alteration in these genes trigger uncontrolled growth and tumour formation. These genes are categorized according to the penetrance level, the proportion of carriers express the associated trait of the mutated gene. Mutations in high penetrance genes such as BRCA1, BRCA2, TP53, PTEN, and SKT11 greatly increase the risk of developing breast cancer. Moderate penetrance gene such as PALB2, ATM, CHEK2, BARD1, BRIP1 and low penetrance gene such as PARP4, CASP8, TOX3 confer moderate to low increase risk of developing breast cancer. Aim of this review is to summarize genes associated with hereditary breast cancer according to their penetrance level (high, moderate and low penetrance).

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 Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

2020 ◽  
Author(s):  
Doris Zodinpuii ◽  
Bawitlung Zothankima ◽  
Jeremy Lalrinsanga Pautu ◽  
Doris Lallawmzuali ◽  
Ashok Kumar Varma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Cancer Susceptibility ◽  
Mutation Screening ◽  
Susceptibility Gene ◽  
Gene Mutations ◽  
Brca1 Gene ◽  
Breast Cancer Susceptibility ◽  
Breast Cancer Susceptibility Gene ◽  
Cancer Susceptibility Genes

Abstract Background: Breast cancer is the most prevalent cancer and leading cause of death among women globally. The present study focuses on screening germline mutations of breast cancer susceptibility genes among the unexplored Mizo breast cancers of culturally and historically homogenous population, living a unique life style habits in terms of diet and tobacco usage. Methods Mutation screening was performed using Sanger sequencing in complete coding region of BRCA1 and frequently mutated exons of TP53, PTEN, CDH1, CHEK2 and XRCC2. Several online mutation prediction tools and databases were used to check the pathogenicity of the polymorphisms observed. Results: We observed eight polymorphisms in total, in which, one variants p.P1544P in BRCA1 gene was found to be novel. No variants were found to have a potential impact on protein since all the polymorphisms are of silent substitutions. No genetic alteration was observed in the studied exons of each of TP53, PTEN, CDH1, CHEK2 and XRCC2. Conclusion: To our knowledge, the present study focusing on familial breast cancer is the first time to analyzed the prevalence of breast cancer susceptibility gene mutations using direct sequencing in Mizo population. Even though, we do not find significant amino acid change, our results suggest the need for further evaluation of broader panel genes and a challenge to screen larger sample size to establish the contribution of these gene mutations in this population.

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 Clinical Characteristics of Korean Breast Cancer Patients Who Carry Pathogenic Germline Mutations in Both BRCA1 and BRCA2: A Single-Center Experience

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1306
Author(s):  
Joon Young Hur ◽  
Ji-Yeon Kim ◽  
Jin Seok Ahn ◽  
Young-Hyuck Im ◽  
Jiyun Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Cancer Susceptibility ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Single Center ◽  
Brca1 And Brca2 ◽  
Single Center Experience ◽  
Cancer Susceptibility Genes

There are few reports of breast cancer patients who carry germline mutations in both germline breast cancer susceptibility genes 1 (gBRCA1) and 2 (gBRCA2). In this study, we analyzed the clinical, pathological, and genomic characteristics of Korean breast cancer patients with both gBRCA1 and gBRCA2 mutations. Medical records of patients who received gBRCA1 and gBRCA2 testing at Samsung Medical Center between January 2007 to October 2018 were retrospectively reviewed. Genomic DNA was isolated from peripheral blood leukocytes. Among a total of 2720 patients, four patients with both gBRCA1 and gBRCA2 mutations were identified (4/2720; 0.14%). Seven patients who had a gBRCA1 mutation and gBRCA2 variants of uncertain significance (VUS) were also identified. In those patients with both gBRCA1 and gBRCA2 mutations, the mean age at diagnosis for breast cancer was 36 years (range, 31–43 years). All four tumors were infiltrating ductal carcinomas and three of the tumors were estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative (triple-negative). All four patients who carried germline mutations in both BRCA1 and BRCA2 had a family history of breast/ovarian cancer. Pathologic stage was II in three patients and I in one patient. Breast cancer patients with both gBRCA1 and gBRCA2 mutations were rare, young at diagnosis, and all but one tumor was triple-negative based on our single-center experience.

Hereditary breast cancer: from molecular pathology to tailored therapies

2008 ◽  
Vol 61 (10) ◽  
pp. 1073-1082 ◽  
Author(s):  
D S P Tan ◽  
C Marchiò ◽  
J S Reis-Filho
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Fanconi Anaemia ◽  
Breast Cancer Susceptibility Gene ◽  
Tumour Suppressor Genes ◽  
Histopathological Diagnosis ◽  
Breast Carcinomas ◽  
High Penetrance

Hereditary breast cancer accounts for up to 5–10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document