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NCI CANCERLIT^® Search: BRCA1 Gene - August 2002

National Cancer Institute^®
Last Modified: August 1, 2002

Breast cancer risks: some clinically useful approaches.
Prophylactic bilateral mastectomy: patterns of practice.
The BRCA1 suppressor hypothesis: an explanation for the tissue-specific tumor development in BRCA1 patients.
Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer.
Biallelic inactivation of BRCA2 in Fanconi anemia.
Transitional cell ovarian carcinoma in a BRCA1 mutation carrier.
BRCA1 germline mutation presenting as an adenocarcinoma of unknown primary.
BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation.
Sample size and power determination for clustered repeated measurements.
Microglandular adenosis of the breast in a BRCA1 mutation carrier: radiological features.

Table of Contents

1
UI - 12116602
AU - Kelly PT
TI - Breast cancer risks: some clinically useful approaches.
SO - Curr Womens Health Rep 2002 Apr;2(2):128-33
AD - Cancer Risk Assessment, Saint Francis Memorial Hospital, 824 Cragmont Avenue, Berkeley, CA 94708, USA. ptkelly@ptkelly.com
Information about breast cancer risk is often confusing and may even be misleading when presented as a comparison of one risk versus another. Frequently used comparison formats include relative risks, odds ratios, and proportional risk reductions. This paper discusses five areas of breast cancer risk--average risk, prognosis following a breast cancer diagnosis, risk associated with use of hormone replacement therapy at menopause, use of tamoxifen as prevention, and risks associated with BRCA mutations--to show the clarity and clinical usefulness that are obtained when risks are presented not as comparisons, but in absolute terms with a time frame.

2
UI - 12124821
AU - Metcalfe KA; Goel V; Lickley L; Semple J; Narod SA
TI - Prophylactic bilateral mastectomy: patterns of practice.
SO - Cancer 2002 Jul 15;95(2):236-42
AD - The Centre for Research in Women's Health, Toronto, Ontario, Canada.
BACKGROUND: Many women who are at an elevated risk of developing breast carcinoma choose prophylactic mastectomy to decrease their risk. We conducted a population-based study to review the indications for, and patterns of practice of prophylactic mastectomy in Ontario, Canada, since 1991. METHODS: A medical chart review was conducted at 33 hospitals that were identified as having conducted at least one prophylactic mastectomy. All bilateral mastectomy patients with no diagnosis of invasive or in situ breast carcinoma were eligible. RESULTS: The number of prophylactic bilateral mastectomies performed varied from 6 to 19. The mean age of women undergoing prophylactic mastectomy was 43.5 years. Eighty percent of the women had prophylactic mastectomy performed because of a family history of breast carcinoma (89 of 99) or because of a known BRCA1 or BRCA2 mutation (10 of 99). Twenty percent of the women had no family history, but had the surgery for other benign breast conditions. Women with a family history of breast carcinoma were much more likely to have a total mastectomy (89%) than a subcutaneous mastectomy (11%). Sixty percent of the women had reconstructive surgery following mastectomy. CONCLUSIONS: Prophylactic mastectomy is not performed on a large scale. The introduction of genetic testing for BRCA1 and BRCA2 has the potential to change the patterns of practice for prophylactic mastectomy. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10680

3
UI - 12086871
AU - Elledge SJ; Amon A
TI - The BRCA1 suppressor hypothesis: an explanation for the tissue-specific tumor development in BRCA1 patients.
SO - Cancer Cell 2002 Mar;1(2):129-32

4
UI - 12124354
AU - Chan KY; Ozcelik H; Cheung AN; Ngan HY; Khoo US
TI - Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer.
SO - Cancer Res 2002 Jul 15;62(14):4151-6
AD - Department of Pathology, Queen Mary Hospital and the University of Hong Kong, Hong Kong.
Hypermethylation of the BRCA1 promoter has previously been shown to cause reduced mRNA expression in both breast and ovarian cancers. Nothing is yet known of the expression pattern or methylation status of the promoter region of BRCA2 in sporadic ovarian cancer. Whereas our analysis of 30 sporadic ovarian carcinomas showed a statistically significant reduction of BRCA1 mRNA expression (P = 0.001), it also showed, in contrast, overexpression of BRCA2 mRNA (P = 0.002) in tumor compared with nontumor. Hypermethylation of the BRCA1 promoter highly correlated with decreased BRCA1 expression (P = 0.017). Methylated CpGs at the BRCA2 promoter were either absent or at very low levels in tumor DNA, whereas they were present at high levels in nontumor DNA. Such hypomethylation also correlated with elevated levels of BRCA2 mRNA (P = 0.043) and showed a statistically significant correlation with tumor stage (P = 0.037). This supports the role of methylation in BRCA2 contributing to the pathogenesis of sporadic ovarian cancer. Furthermore, 14 (58.2%) and 9 (56.3%) of all of the cases with aberrant BRCA mRNA expression and methylation patterns, respectively, demonstrated opposing mRNA expression and methylation patterns of the BRCA1 and BRCA2 genes within the same cases. Our findings suggest that both genes may be involved in the development of sporadic ovarian cancer.

5
UI - 12065746
AU - Howlett NG; Taniguchi T; Olson S; Cox B; Waisfisz Q; De Die-Smulders C;
TI - Persky N; Grompe M; Joenje H; Pals G; Ikeda H; Fox EA; D'Andrea AD Biallelic inactivation of BRCA2 in Fanconi anemia.
SO - Science 2002 Jul 26;297(5581):606-9
AD - Department of Pediatric Oncology, Children's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations.

6
UI - 12151180
AU - Werness BA; DiCioccio RA
TI - Transitional cell ovarian carcinoma in a BRCA1 mutation carrier.
SO - Obstet Gynecol 2002 Aug;100(2):385; discussion 385

7
UI - 10882335
AU - Klein P; Prolla G; Wallach R; Melamed J; Muggia FM
TI - BRCA1 germline mutation presenting as an adenocarcinoma of unknown primary.
SO - Cancer J 2000 May-Jun;6(3):188-90
BACKGROUND: The work-up of adenocarcinoma of unknown primary usually includes history, physical examination, radiographic imaging, tumor markers, and more recently molecular and genetic information. We report here on how the suggestion by family history of a BRCA1 mutation guided the diagnostic and therapeutic approach in a patient with metastatic carcinoma of unknown primary. METHODS: BRCA1 mutation was screened for by polymerase chain reaction (PCR) and single-strand conformational polymorphism analysis. Primers for PCR amplification included selected BRCA1 exons 2, 110, 11L, 13, and 20. The PCR product was cloned into a PCRII vector and sequenced with a Sequenase Version 2.0 Sequencing Kit. RESULTS: Single-strand conformational polymorphism analysis suggested a mutation in the region of exon 20 and sequencing confirmed the presence of a germline mutation 5382insC. CONCLUSIONS: This case illustrates an unusual presentation of adenocarcinoma of unknown primary in a patient with a germline BRCA1 mutation, the use of a suspected germline mutation to guide the work-up and treatment, and finally the value of positron emission tomography scanning in the work-up of an unknown primary.

8
UI - 12170778
AU - Takimoto R; MacLachlan TK; Dicker DT; Niitsu Y; Mori T; el-Deiry WS
TI - BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation.
SO - Cancer Biol Ther 2002 Mar-Apr;1(2):177-86; discussion 187-8
AD - Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Departments of Medicine, Genetics, and Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
The p53 and BRCA1 tumor suppressors are involved in repair processes and may cooperate to transactivate certain genes, including p21WAF/CIP1 and GADD45. We find that the Xeroderma Pigmentosum Complementation group E (XPE) mutated Damaged-DNA binding protein p48 (DDB2) is upregulated by BRCA1 in a p53-dependent manner following UVC, Adriamycin, or Cisplatin exposure. BRCA1 enhances p53 binding to the DDB2 promoter in vivo as well as p53-dependent transactivation of DDB2 promoter-reporter constructs through a classical p53 DNA responsive element. Antisense abrogation of BRCA1 expression abrogates upregulation of DDB2 after UVC or cisplatin exposure. Using a host cell reactivation assay, DNA repair activity is more significantly restored by introduction of BRCA1 into wt as compared to DDB2-deficient cells. Furthermore disappearance of the photoproducts cyclobutane pyrimidine dimer (CPD) and 6-4 photoproduct (6-4PP) was delayed by antisense abrogation of BRCA1 expression in UV-exposed human cells. Thus the DNA repair function of BRCA1 may be attributed in part to p53-dependent transcriptional induction of DDB2. Loss of BRCA1-dependent DDB2 repair function may contribute to cancer susceptibility and cellular sensitivity to DNA damage.

9
UI - 12111912
AU - Liu A; Shih WJ; Gehan E
TI - Sample size and power determination for clustered repeated measurements.
SO - Stat Med 2002 Jun 30;21(12):1787-801
AD - Biostatistics Unit, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA. liual@gunet.gerogetown.edu
It is common in epidemiological and clinical studies that each subject has repeated measurements on a single common variable, while the subjects are also 'clustered'. To compute sample size or power of a test, we have to consider two types of correlation: correlation among repeated measurements within the same subject, and correlation among subjects in the same cluster. We develop, based on generalized estimating equations, procedures for computing sample size and power with clustered repeated measurements. Explicit formulae are derived for comparing two means, two slopes and two proportions, under several simple correlation structures. Copyright 2002 John Wiley & Sons, Ltd. abstract

10
UI - 12042957
AU - Sabate JM; Gomez A; Torrubia S; Matias-Guiu X; Alonso C; Pericay C; Diaz
TI - O Microglandular adenosis of the breast in a BRCA1 mutation carrier: radiological features.
SO - Eur Radiol 2002 Jun;12(6):1479-82
AD - Department of Diagnostic Radiology, Hospital de Sant Pau, Universitat Autonoma de Barcelona, Sant Antoni M. Claret, 167, 08025 Barcelona, Spain.
Microglandular adenosis is a very uncommon benign proliferative disorder of the breast that may mimic tubular carcinoma radiologically and pathologically. We describe the radiological features of this rare condition in a patient with BRCA 1 mutation. To our knowledge, this is the first case of microglandular adenosis reported in the radiology literature. The relationship between microglandular adenosis and malignancy and the association between BRCA 1 and proliferative benign disorders are also discussed.

The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.

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