Mutation analysis of the BCCIP gene for breast cancer susceptibility in breast/ovarian cancer families

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.

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Risk Estimation as a Decision-Making Tool for Genetic Analysis of the Breast Cancer Susceptibility Genes

Disease Markers ◽

10.1155/1999/238375 ◽

1999 ◽

Vol 15 (1-3) ◽

pp. 53-65 ◽

Cited By ~ 5

Author(s):

Jenny Chang-Claude ◽

Heiko Becher ◽

Maria Caligo ◽

Diana Eccles ◽

Gareth Evans ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Familial Breast Cancer ◽

Genetic Model ◽

Germ Line ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Cancer Gene ◽

Brca2 Mutations ◽

Breast Cancer Gene

For genetic counselling of a woman on familial breast cancer, an accurate evaluation of the probability that she carries a germ-line mutation is needed to assist in making decisions about genetic-testing.We used data from eight collaborating centres comprising 618 families (346 breast cancer only, 239 breast or ovarian cancer) recruited as research families or counselled for familial breast cancer, representing a broad range of family structures. Screening was performed in affected women from 618 families for germ-line mutations in BRCA1 and in 176 families for BRCA2 mutations, using different methods including SSCP, CSGE, DGGE, FAMA and PTT analysis followed by direct sequencing. Germ-line BRCA1 mutations were detected in 132 families and BRCA2 mutations in 16 families. The probability of being a carrier of a dominant breast cancer gene was calculated for the screened individual under the established genetic model for breast cancer susceptibility, first, with parameters for age-specific penetrances for breast cancer only [7] and, second, with age-specific penetrances for ovarian cancer in addition [20]. Our results indicate that the estimated probability of carrying a dominant breast cancer gene gives a direct measure of the likelihood of detecting mutations in BRCA1 and BRCA2. For breast/ovarian cancer families, the genetic model according to Narod et al. [20] is preferable for calculating the proband's genetic risk, and gives detection rates that indicate a 50% sensitivity of the gene test. Due to the incomplete BRCA2 screening of the families, we cannot yet draw any conclusions with respect to the breast cancer only families.

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Genistein induces apoptosis in ovarian cancer cells via different molecular pathways depending on Breast Cancer Susceptibility gene-1 (BRCA1) status

European Journal of Pharmacology ◽

10.1016/j.ejphar.2008.04.041 ◽

2008 ◽

Vol 588 (2-3) ◽

pp. 158-164 ◽

Cited By ~ 16

Author(s):

Karedath Abdul Aziz Thasni ◽

Gopakumaran Rojini ◽

S. Nair Rakesh ◽

Thankappan Ratheeshkumar ◽

Mani Shankar Babu ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Susceptibility ◽

Susceptibility Gene ◽

Breast Cancer Susceptibility ◽

Ovarian Cancer Cells ◽

Breast Cancer Susceptibility Gene ◽

Molecular Pathways ◽

Cancer Susceptibility Gene ◽

Brca1 Status

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Analysis of breast cancer susceptibility genesBRCA1 andBRCA2 in Thai familial and isolated early-onset breast and ovarian cancer

Human Mutation ◽

10.1002/humu.9049 ◽

2002 ◽

Vol 20 (3) ◽

pp. 230-230 ◽

Cited By ~ 14

Author(s):

Pimpicha Patmasiriwat ◽

Kris Bhothisuwan ◽

Olga M. Sinilnikova ◽

Sandrine Chopin ◽

Suthida Methakijvaroon ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Early Onset ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Breast And Ovarian Cancer

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Absence of the CHEK2 c.1100delC mutation in familial breast and ovarian cancer in Colombia: a case-control study

F1000Research ◽

10.12688/f1000research.13368.1 ◽

2018 ◽

Vol 7 ◽

pp. 1032 ◽

Cited By ~ 1

Author(s):

Ana-Lucia Rivera-Herrera ◽

Laura Cifuentes-C ◽

JA Gil-Vera ◽

Guillermo Barreto

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Brca1 And Brca2 ◽

Specific Pcr ◽

Breast Cancer Predisposition ◽

Predisposition Genes ◽

Allele Specific ◽

Allele Specific Pcr

Background: BRCA1 and BRCA2 have been identified as high-penetrance breast cancer predisposition genes, but they only account for a small fraction of the inherited component of breast cancer. To explain the remaining cases, a polygenic model with a large number of low- to moderate-penetrance genes have been proposed; one of these, is the CHEK2 gene (Checkpoint Kinase 2). The objective of this study was to determine the role of the CHEK2 gene, specifically the c.1100delC mutation in familial breast cancer susceptibility in Colombian patients. Methods: We screened 131 high-risk breast and/or ovarian cancer patients (negative for mutations in BRCA1 and BRCA2) and 131 controls for the germline mutation CHEK2 c.1100delC by allele-specific PCR. Results: None of the cases or controls showed the CHEK2 c.1100delC mutation, neither as a homozygote nor as a heterozygote. Conclusions: Our results suggest that the CHEK2 c.1100delC mutation is not a risk factor for genetic susceptibility to familial breast or ovarian cancer in the Colombian population. The absence of the CHEK2 c.1100delC mutation in our population show the importance of considering ethnic background before offering a genetic test.

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

Journal of Clinical Oncology ◽

10.1200/jco.2002.05.121 ◽

2002 ◽

Vol 20 (11) ◽

pp. 2701-2712 ◽

Cited By ~ 332

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.

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Breast cancer susceptibility variants alter risk in familial ovarian cancer

Familial Cancer ◽

10.1007/s10689-010-9349-2 ◽

2010 ◽

Vol 9 (4) ◽

pp. 503-506 ◽

Cited By ~ 2

Author(s):

A. Latif ◽

H. J. McBurney ◽

S. A. Roberts ◽

F. Lalloo ◽

A. Howell ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Familial Ovarian Cancer

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Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies new candidate susceptibility genes for breast and ovarian cancer

10.1101/2020.04.23.043653 ◽

2020 ◽

Author(s):

Siddhartha P. Kar ◽

Daniel P. C. Considine ◽

Jonathan P. Tyrer ◽

Jasmine T. Plummer ◽

Stephanie Chen ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Prediction Models ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Susceptibility Genes ◽

Susceptibility Loci ◽

Breast And Ovarian Cancer ◽

Cancer Susceptibility Genes ◽

Genomic Regions

AbstractFamilial, genome-wide association (GWAS), and sequencing studies and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWAS) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through novel application of a pleiotropy-guided conditional/conjunction false discovery rate approach for the first time in the setting of a TWAS. This identified 14 new candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 new candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were > 1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. Overlaying candidate causal risk variants identified by GWAS fine mapping onto expression prediction models for genes at known loci suggested that the association for 55% of these genes was driven by the underlying GWAS signal.SignificanceThe 22 new genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.

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