scholarly journals BRCA1 and BRCA2 genes mutation analysis in patients with a family history of breast and ovarian cancer

2004 ◽  
Vol 23 (3) ◽  
pp. 271-277 ◽  
Author(s):  
Irene Konstantopoulou ◽  
Radmila Jankovic ◽  
Lidija Raicevic ◽  
Angela Ladopoulou ◽  
Sophia Armaou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Direct Sequencing ◽  
Brca1 Gene ◽  
Greek Population ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Recurrent Mutations ◽  
Brca1 And Brca2 Genes ◽  
History Of

Hereditary breast and ovarian cancer syndromes can be caused by loss-of-function germline mutations in one of the tumor suppressor genes BRCA1 and BRCA2. In order to characterize these mutations in the Greek population we have been collecting samples from breast/ovarian cancer patients with a family history in collaboration with a large number of Greek Hospitals. Our DNA bank contains samples from more than 300 patients, corresponding to approximately 250 families. In terms of family history this group consists of three subgroups: (I) very early onset (<30 yrs) without family history (10%); (II) moderate family history (2 members affected, < 50 yrs) (40 %) (III) strong family history (3?7 members affected) (50 %). Screening of BRCA1 and BRCA2 genes in 150 patients has revealed deleterious mutations in 39 unrelated patients. 5382insC has been found in 11 unrelated families. In summary, the mutation spectrum of BRCA1 and BRCA2 genes in the Greek population seems to be composed by an elevated frequency of 5382insC with the rest being novel or recurrent mutations with low frequency in both genes. Screening of BRCA1 gene is also in progress in collaboration with the Institute of Oncology and Radiology of Serbia. DNA samples have been collected from 32 Serbian families with a family history of breast ovarian cancer. Direct sequencing in exons 2, 5 and 20 of all these samples revealed only one deleterious mutation (C61G) in exon 5 of BRCA1 gene. Screening of the remaining exons is in progress.

Identifying genomic rearrangements in BRCA1 and BRCA2 in high-risk individuals for hereditary breast and ovarian cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 163-163 ◽  
Author(s):  
M. Jackson ◽  
D. Mattair ◽  
H. Lin ◽  
A. M. Gutierrez-Barrera ◽  
N. Elsayegh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Large Scale ◽  
Cancer Center ◽  
Tumor Characteristics ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Patient Request ◽  
History Of

163 Background: Germline mutations in the BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancer (HBOC). Comprehensive gene sequencing detects ~87% of BRCA mutations, and large genomic rearrangement testing (BART) accounts for ~3%. Criteria have been established to capture individuals who most likely have a BART mutation, however, recent data shows that some individuals have BART mutations and do not meet the criteria. We conducted a single-institution study to evaluate the sufficiency of BART criteria to determine if new criteria are warranted. Methods: During 2006-2008, 172 individuals underwent BRCA sequencing and BART at M. D. Anderson Cancer Center. A retrospective, IRB-approved chart review of a prospectively maintained database was conducted to determine BART criteria eligibility, personal/family history of breast and ovarian cancer and tumor characteristics. Univariate and multivariate analysis was performed to test the significance of each variable in relation to BRCA1/BRCA2 positivity. Results: Of 172 individuals, 12/34 (35%) had BRCA1 BART mutations, and 7/11 (64%) had BRCA2 BART mutations. Of the 19 individuals who tested positive for BART mutations, only 8 (42%) met BART criteria and 11 (58%) did not and proceeded with BART for various reasons (family history, insurance covered, and patient request). Individuals who were BRCA1 positive (sequencing or BART) were more likely to have ER/PR negative breast cancer (p<0.0001) and a personal (p=0.0215)/family history of ovarian cancer (p=0.0001) compared to non-carriers and individuals who had no family history Individuals who were BRCA1 sequencing positive were more likely to meet BART criteria than BRCA1 BART positive (p=0.0151) individuals. Conclusions: Given that no significant differences in family history/tumor characteristics between individuals who have sequencing and BART mutations were identified, and a majority of individuals who were BART positive do not meet BART criteria, it appears that these criteria may be insufficient. BART testing should be considered for all individuals who undergo BRCA sequencing; however, large scale collaboration studies should be conducted.

scholarly journals Application of a Polygenic Model of Breast and Ovarian Cancer to Critical Illness Insurance

2006 ◽  
Vol 1 (2) ◽  
pp. 319-343 ◽  
Author(s):  
A. S. Macdonald ◽  
K. R. McIvor
Keyword(s):  
Ovarian Cancer ◽  
Critical Illness ◽  
Family History ◽  
Brca1 And Brca2 ◽  
Additional Risk ◽  
Genetic Test Results ◽  
Brca1 And Brca2 Genes ◽  
Polygenic Component ◽  
History Of ◽  
Premium Rates

ABSTRACTMutations in the BRCA1 and BRCA2 genes confer very high risk of breast cancer (BC), but only account for about 25% of the observed familial clustering of BC. Antoniou et al. (2002) proposed a model which included the BRCA1 and BRCA2 genes, and a polygenic component which acted multiplicatively on the rate of onset of BC. We use this model to find premium rates for critical illness insurance: (a) given knowledge of an applicant's polygenotype; and (b) given knowledge of a family history of BC or ovarian cancer. We find that the polygenic component causes large variation in premium rates even among non-mutation carriers, therefore affecting the whole population. In some cases the polygenic contribution is protective enough to reduce or remove the additional risk of a BRCA1/2 mutation, leading to cases where it will be advantageous to disclose genetic test results which are adverse in absolute terms. Premiums based on family history are lower than those found in an earlier study which attributed all genetic BC risk to the BRCA1/2 genes.

Risk factors for lymph node metastasis of ovarian, fallopian tube and primary peritoneal cancer in hereditary breast and ovarian cancer syndrome

2020 ◽  
Vol 50 (12) ◽  
pp. 1380-1385
Author(s):  
Takashi Mitamura ◽  
Masayuki Sekine ◽  
Masami Arai ◽  
Yuka Shibata ◽  
Momoko Kato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Family History ◽  
Lymph Node Metastasis ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Node Metastasis ◽  
Increased Risk ◽  
History Of

Abstract Background To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis. Methods We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing. Results We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA− (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA− (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T &gt; A and c.2800C &gt; T. Conclusions This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy.

scholarly journals A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca1 Gene ◽  
Pathogenic Mutation ◽  
Compound Heterozygous ◽  
Strong Family History ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Mutations ◽  
Increased Risk ◽  
History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

Screening RAD51C nucleotide alterations in patients with a family history of breast and ovarian cancer

2010 ◽  
Vol 124 (3) ◽  
pp. 857-861 ◽  
Author(s):  
Yonglan Zheng ◽  
Jing Zhang ◽  
Kisha Hope ◽  
Qun Niu ◽  
Dezheng Huo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Breast And Ovarian Cancer ◽  
History Of

Identification of Women at Risk for Hereditary Breast and Ovarian Cancer in A Sample of 1000 Slovenian Women: A Comparison of Guidelines

2020 ◽  
Author(s):  
Urška Kotnik ◽  
Borut Peterlin ◽  
Luca Lovrecic
Keyword(s):  
Ovarian Cancer ◽  
At Risk ◽  
Family History ◽  
High Risk ◽  
Breast And Ovarian Cancer ◽  
Nccn Guidelines ◽  
Family History Of Cancer ◽  
Slovenian Population ◽  
History Of ◽  
History Of Cancer

Abstract Background: An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines.Methods: Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored. Results: NCCN guidelines identify 16.7 % of women, ACMG/NSGC guidelines identify 7.1 % of women, and SGO guidelines identify 7.0 % of women from the Slovenian population, while 6.2 % of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer.Conclusions: We identified 17.4 % of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying more than twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

Molecular genetic testing for large genomic deletion and duplication mutations in the BRCA1 and BRCA2 genes for hereditary breast and ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10513-10513
Author(s):  
R. Wenstrup ◽  
T. Judkins ◽  
K. Eliason ◽  
J. Schoenberger ◽  
S. Rajamani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Superior Performance ◽  
Brca1 And Brca2 ◽  
Large Rearrangement ◽  
Genomic Deletion ◽  
Large Genomic Deletion ◽  
Panel Testing ◽  
Brca1 And Brca2 Genes ◽  
Risk Patients

10513 Background: Mutations in the BRCA1 and BRCA2 genes are comprised of a majority of mutations that are detectable by sequence analysis, and a minority of large genomic deletion and duplication mutations that are detected by methods different than sequencing. Our laboratory developed and implemented a clinical assay for large rearrangements that we refer to as BART (BRCA1/2 Rearrangement Test). We validated the performance of BART using a completely anonymous large number of breast/ovarian cancer patient samples. We also demonstrated superior performance of BART versus other dosage-sensitive methods including Multiplex Ligation-dependent Probe Amplification (MLPA). Methods: BART utilizes quantitative endpoint polymerase chain reaction (PCR) in a multiplexed fluorescent format. Eleven multiplex PCR reactions were designed to contain two amplicons targeting the promoter region, all coding exons, and flanking regions of BRCA1 and BRCA2. An automated likelihood-based analysis application normalizes target amplicon copy number between BRCA1, BRCA2 and three control genes. Deletions and duplications are identified with a statistical confidence level. Results: Based on clinical and family history criteria, 1,035 patients were identified as severe-risk during the initial months of clinical BART analysis at Myriad Genetic Laboratories. All patients were initially tested for Comprehensive BRACAnalysis which includes BRCA1 and BRCA2 full gene sequencing plus large rearrangement panel testing for 5 recurrent BRCA1 mutations. Among severe-risk patients, 302 (29.2%) were positive for a BRCA1 or BRCA2 mutation by sequencing, 9 (0.9%) were positive by large rearrangement panel testing and an additional 27(2.6%) tested positive by BART for large genomic rearrangements. The total detection rate for deleterious mutations in severe-risk individuals was therefore 32.7%. Conclusions: Our initial clinical data indicate that BART testing is appropriate for high-risk patients identified on the basis of personal and family history criteria. No significant financial relationships to disclose.

scholarly journals Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women

SpringerPlus ◽  
2014 ◽  
Vol 3 (1) ◽  
pp. 727 ◽  
Author(s):  
Kristin Anderson ◽  
Patricia A Thompson ◽  
Betsy C Wertheim ◽  
Lorena Martin ◽  
Ian K Komenaka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Family History ◽  
Triple Negative ◽  
Latina Women ◽  
Breast And Ovarian Cancer ◽  
History Of ◽  
Triple Negative Subtype
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