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BRCA1 and Breast Neoplasms (1 - 50 of 198)
PMID: 10023017
Structure and expression of variant BRCA2a lacking the transactivation domain.
BRCA1 and ... familial breast cancers and ... Both BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
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PMID: 10023017

Structure and expression of variant BRCA2a lacking the transactivation domain.
Source

Oncology reports (0)

Abstract

BRCA1 and BRCA2 are tumor suppressor genes shown to be involved in 90% of familial breast cancers and also known to be involved in ovarian and prostate cancers. Both BRCA1 and BRCA2 gene products are regulated in a cell cycle-dependent manner and have potential transactivation function. Here, we show that BRCA2 undergoes differential splicing giving rise to a novel variant protein BRCA2a, lacking putative transcriptional activation domain. Both BRCA2a and BRCA2 are expressed at high levels in thymus and testis but moderate levels in mammary gland and prostate suggesting that BRCA2a and BRCA2 may have a role in the development and differentiation of these tissues.

PMID: 10023316
Current policies for surveillance and management in women at risk of breast and ovarian cancer: a survey among 16 European family cancer clinics. European Familial Breast Cancer Collaborative Group.
... of breast cancer predisposing ... ( BRCA1 and ... Familial Breast Cancer Collaborative ... of breast cancer in ... in BRCA1 and ... familial breast cancer used ...   (details)

BRCA1 and Breast Neoplasms

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PMID: 10023316

Current policies for surveillance and management in women at risk of breast and ovarian cancer: a survey among 16 European family cancer clinics. European Familial Breast Cancer Collaborative Group.
Source

European journal of cancer (Oxford, England : 1990; November 1998)

Abstract

The recent isolation of breast cancer predisposing genes ( BRCA1 and BRCA2) allows the identification of carriers within affected families. These carriers have a 50-85% risk of developing breast or ovarian cancer and need careful follow-up. The purpose of this study was to evaluate the management and screening protocols implemented in high risk families at various family cancer clinics in Europe. A questionnaire was mailed to the members of the European Familial Breast Cancer Collaborative Group (n = 30) requesting information on the following issues: indication for surveillance of breasts and ovaries, the recommended protocol, coordination of the screening examination, prophylactic surgery, the specific management of breast cancer in a mutation carrier and the use of oestrogen. 16 centres from nine countries responded. Most centres recommend surveillance of the breasts if the lifetime risk exceeds 15-20%. The surveillance protocol that is generally advised comprises monthly self breast examination, examination by a specialist every 6 months and annual mammography, all starting from an age between 25 and 35 years. Surveillance of the ovaries is recommended in BRCA1 and BRCA2-mutation carriers, in members from breast/ovarian cancer families and in some centres in 'breast cancer only' families with an early onset of breast cancer. The recommended protocol includes gynaecological examination, sonography and estimation of CA-125 at yearly intervals starting from the age 30-35 years. Prophylactic mastectomy is considered for proven mutation carriers in some centres. Most centres consider prophylactic oophorectomy in mutation carriers and some centres also consider it for members of breast/ovarian cancer families. This survey provides insight into the guidelines for surveillance and management of familial breast cancer used at various family cancer clinics in Europe; this insight may contribute to the appropriate management of these high risk women. It should be emphasised that most recommendations are based on experts' opinion rather than on any specific studies.

PMID: 10026184
Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1.
Breast cancer 1 (BRCA1) and ... the BRCA1 /BARD1 ... of BRCA1 and ... Shorter BRCA1 RING ... longer BRCA1 constructs, ... of BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
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2 votes   Error

Comments

PMID: 10026184

Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1.
Source

The Journal of biological chemistry (2/26/1999)

Abstract

Breast cancer 1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1) are multidomain proteins that interact in vivo via their N-terminal RING finger motif regions. To characterize functional aspects of the BRCA1/BARD1 interaction, we have defined the structural domains required for the interaction, as well as their oligomerization state, relative stability, and possible nucleic acid binding activity. We have found that the RING finger motifs do not themselves constitute stable structural domains but are instead part of larger domains comprising residues 1-109 of BRCA1 and residues 26-119 of BARD1. These domains exist as homodimers and preferentially form a stable heterodimer. Shorter BRCA1 RING finger constructs do not interact with BARD1 or with longer BRCA1 constructs, indicating that the heterodimeric and homodimer interactions are mediated by regions outside the canonical RING finger motif. Nucleic acid binding is a generally proposed function of RING finger domains. We show that neither the homodimers nor the heterodimer displays affinity for nucleic acids, indicating that the proposed roles of BRCA1 and BARD1 in DNA repair and/or transcriptional activation must be mediated either by other regions of the proteins or by additional cofactors.

PMID: 10030809
The genetic basis of breast cancer and its clinical implications.
... of breast cancer cases ... hereditary breast cancer may ... including BRCA1 , ... all breast cancers are ... with BRCA1 and ... of breast cancer families ... to breast cancer has ... developing breast cancer and ... in breast cancer treatment, ... of breast cancer management.   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
1 votes   Significant
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PMID: 10030809

The genetic basis of breast cancer and its clinical implications.
Source

The Australian and New Zealand journal of surgery (February 1999)

Abstract

While it has long been recognized that a proportion of breast cancer cases are the result of an inherited familial predisposition, precise knowledge of the underlying genetic processes has been lacking. Recent advances in molecular biology, however, have shown that hereditary breast cancer may eventuate as a result of mutations on several specific gene loci including BRCA1, BRCA2, ATM gene, PTEN and p53. Several other less frequently occurring predisposition genes such as the androgen receptor gene (AR), the HNPCC genes and the oestrogen receptor gene may also be involved, but to a lesser extent. Overall, approximately 5-10% of all breast cancers are thought to involve one of these inherited predisposition genes, with BRCA1 and BRCA2 being responsible for as much as 90% of this group. Because of the complex nature of genetic testing, mutation analysis is not presently routinely available outside genetic counselling clinics. In this review the current knowledge and role of each predisposition gene is outlined and the management implications of genetic testing for members of breast cancer families for both affected and non-affected members are discussed. The need to provide comprehensive counselling for women with an inherited predisposition to breast cancer has seen the evolution of the familial cancer clinic, involving a multidisciplinary specialist team approach. Familial cancer clinics will provide individuals with information about their risk of developing breast cancer and offer advice regarding further management strategies. It is important that surgeons, who have traditionally played a key role in breast cancer treatment, remain cognizant of these advances in genetic molecular biology, and in so doing continue to remain key participants in the conduct of breast cancer management.

PMID: 10036974
Mutations in the BRCA1 gene: implications of inter-population differences for predicting the risk of radiation-induced breast cancers.
... of BRCA1 mutant ... radiation-induced breast cancer risks ... cumulative breast cancer risk ...   (details)

BRCA1 and Breast Neoplasms

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PMID: 10036974

Mutations in the BRCA1 gene: implications of inter-population differences for predicting the risk of radiation-induced breast cancers.
Source

Genetical research (December 1998)

Abstract

The effects of cancer predisposition and increased tumorigenic radiosensitivity of the predisposed genotypes on radiation cancer risks (in the general population and in sisters and first cousins of affected probands) are studied using an autosomal dominant model of cancer predisposition and radiosensitivity. The model assumes that the predisposing alleles, which confer enhanced tumorigenic radiosensitivity, are incompletely penetrant. In addition, the model also allows for sporadic cancers, unrelated to the predisposing locus. The predictions of the model are illustrated using current estimates of BRCA1 mutant gene frequencies; the estimates of the strength of predisposition and radiosensitivity differentials used are based on animal and human studies. It is shown that, unless both the strength of predisposition and radiosensitivity differential are large (say, > 100-fold in comparison with normal homozygotes), (i) the effect of risk heterogeneity on cancer risk is marginal; (ii) dose-dependent radiation effect remains virtually the same as in a homogeneous irradiated population that has no predisposed subgroups; (iii) for the same radiation dose, relatives of affected probands show an enhancement of cancer risks; and (iv) most extra cancers in relatives can be attributed to radiosensitivity differentials. This simple model can give an upper bound of the effect of risk heterogeneity on radiation-induced breast cancer risks even when the cumulative breast cancer risk is age-dependent. Further, our model predicts that the benefits of mammography outweigh the risks.

PMID: 10037104
Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.
... in BRCA1 and/or ... in BRCA1 and ... in BRCA1 and ... their BRCA1 and/or ... with breast cancer and ... with breast cancer and ... after breast cancer were ... of BRCA1 and/or ... of BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

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PMID: 10037104

Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.
Source

Journal of the National Cancer Institute (2/3/1999)

Abstract

[BACKGROUND] Studies of survival following breast and ovarian cancers in BRCA1 and/or BRCA2 mutation carriers have yielded conflicting results. We undertook an analysis of a community-based study of Ashkenazi Jews to investigate the effect of three founder mutations in BRCA1 and BRCA2 on survival among patients with breast or ovarian cancer. [METHODS] We collected blood samples and questionnaire data from 5318 Ashkenazi Jewish volunteers. The blood samples were tested for 185delAG (two nucleotide deletion) and 5382insC (single nucleotide insertion) mutations in BRCA1 and the 6174delT (single nucleotide deletion) mutation in BRCA2. To estimate survival differences in the affected relatives according to their BRCA1 and/or BRCA2 mutation carrier status, we devised and applied a novel extension of the kin-cohort method. [RESULTS] Fifty mutation carriers reported that 58 of their first-degree relatives had been diagnosed with breast cancer and 10 with ovarian cancer; 907 noncarriers reported 979 first-degree relatives with breast cancer and 116 with ovarian cancer. Kaplan-Meier estimates of median survival after breast cancer were 16 years (95% confidence interval [CI] = 11-40) in the relatives of carriers and 18 years (95% CI = 15-22) in the relatives of noncarriers, a difference that was not statistically significant (two-sided P = .87). There was also no difference in survival times among the 126 first-degree relatives with ovarian cancer. We found no survival difference between patients with breast or ovarian cancer who were inferred carriers of BRCA1 and/or BRCA2 mutations and noncarriers. [CONCLUSIONS] Carriers of BRCA1 and BRCA2 mutations appeared to have neither better nor worse survival prognosis.

PMID: 10052688
Isolation, purification and quantification of BRCA1 protein from tumour cells by affinity perfusion chromatography.
... of BRCA1 protein ... against BRCA1 . ... of BRCA1 expressed ... anti- BRCA1 polyclonal ... human breast tumour cell ... in BRCA1 protein ...   (details)

BRCA1 and Breast Neoplasms

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PMID: 10052688

Isolation, purification and quantification of BRCA1 protein from tumour cells by affinity perfusion chromatography.
Source

Journal of chromatography. B, Biomedical sciences and applications (1/22/1999)

Abstract

A new procedure for the isolation, purification and quantification of the product of the oncosuppressor gene brca1 in breast tissues, was carried out. It involves internal cell protein [35S]methionine labelling followed by two perfusion chromatographies. The first one is heparin affinity chromatography, to purify all of the cell DNA-binding proteins. A subsequent specific immunoprecipitation of BRCA1 protein was performed with an antibody raised against BRCA1. The immune complex was isolated using the second chromatographic step, Protein A affinity chromatography. The amount of BRCA1 expressed by cells was expressed as a ratio, in percent, calculated as follows: 100x amount of labelled DNA-binding proteins (dpm) that bound specifically to the anti- BRCA1 polyclonal antibodies (K-18)/amount of whole labelled DNA-binding protein (dpm) purified on a heparin column. Applications to MCF7 and T-47D human breast tumour cell lines, which were treated or not using 2 mM sodium butyrate demonstrated an increase in BRCA1 protein expression.

PMID: 10053113
Frequency of BRCA1 mutation 5382insC in German breast cancer patients.
... the BRCA1 mutation ... German breast cancer patients ... of breast cancer patients ... unselected breast cancer patients ... at BRCA1 introns ... familial breast cancer patients ... frequent BRCA1 mutation ... German breast cancer patients. ... German breast cancer population. ... large breast cancer populations.   (details)

BRCA1 and Breast Neoplasms

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Comments

PMID: 10053113

Frequency of BRCA1 mutation 5382insC in German breast cancer patients.
Source

Gynecologic oncology (March 1999)

Abstract

[OBJECTIVE] The aim of the study was to determine the frequency of the BRCA1 mutation 5382insC in German breast cancer patients with and without prior knowledge of a family history of breast cancer. [METHODS] Two groups of breast cancer patients were tested for the presence or absence of the 5382insC mutation using a PCR primer mismatch assay. A sample of 248 patients unrelated by genealogy was selected based on a history of breast and/or ovarian cancer in the families. In addition, a population-based sample of 800 unselected breast cancer patients was included in the analysis. Three intragenic DNA markers D17S1323, D17S1322, and D17S855, located at BRCA1 introns 12, 19, and 20, respectively, were utilized for allelic association studies as well as for haplotype analysis in 4 breast/ovarian cancer families. [RESULTS] The 5382insC mutation was identified in 10/248 (4.0%) familial breast cancer patients and in 8/800 (1.0%) unselected cases. Allelic association studies and haplotype analysis revealed an association of allele Nos. "6" at D17S1323 (chi2 value = 9.34, P = 0.007), "5" at D17S1322 (chi2 value = 3.62, P = 0.171), and "4" at D17S855 (chi2 value = 11.34, P = 0. 002) with the mutation 5382insC. [CONCLUSION] 5382insC constitutes a frequent BRCA1 mutation in German breast cancer patients. The significant allelic association between this mutation and two intragenic DNA markers (D17S1323, D17S855) and the elevated allele frequency at marker D17S1322 suggest an ancient founder in the German breast cancer population. The PCR primer mismatch assay described herein provides a rapid and reliable detection method for the recurrent 5382insC mutation and will be useful for the analysis of large breast cancer populations.

PMID: 10063581
[Surgical procedure in primary and metastatic breast carcinoma].
... that breast cancer is ... primary breast cancer which ... stage breast cancer patients ... two breast cancer susceptibility genes, BRCA1 and ... for BRCA1 or ... with breast cancer remain ... primary breast cancer patients ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
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Comments

PMID: 10063581

[Surgical procedure in primary and metastatic breast carcinoma].
Source

Zentralblatt für Chirurgie (1998)

Abstract

We know that breast cancer is already a systemic disease in the majority of patients at the time it is first diagnosed, requiring an interdisciplinary treatment concept. This fact has changed the surgical treatment approach of primary breast cancer which currently follows the principle: "As much as necessary, as little as possible". Improved early detection of breast carcinomas allows the treatment of a majority of early stage breast cancer patients with breast-conservation surgery, followed by irradiation except for a few contraindications. Although survival is not significantly different for patients who undergo breast conservation surgery plus irradiation than for those having modified radical mastectomy, the pattern and prognostic value of locoregional failure are different. Locoregional failure after breast conservation requires mastectomy, thoracic wall recurrence will be treated by (en-bloc) resection and irradiation. Following rigorous selection criteria and indications, surgical resection of distant metastases to the liver, lung or brain can improve the quality of life and prolong survival, it should therefore be taken into consideration in individual cases. Since the two breast cancer susceptibility genes, BRCA1 and BRCA2, have been detected, high-risk patients should be offered the possibility of genetic counseling and genetic testing. Based on our present knowledge, the surgical approaches for BRCA1 or BRCA2 mutation carriers with breast cancer remain unchanged. There are some indications that molecular tumor parameters can be used to identify a subgroup of primary breast cancer patients who are characterized by a poorer prognosis. The results achieved in our own patients add further evidence in favor of this theory.

PMID: 10064388
Immunolocalization of BRCA1 protein in normal breast tissue and sporadic invasive ductal carcinomas: a correlation with other biological parameters.
... the BRCA1 gene ... of BRCA1 have ... in breast cancer lines ... of breast cancer tissues. ... of BRCA1 in ... The BRCA1 expression ... immunohistochemistry. BRCA1 expression ... age. BRCA1 was ... nuclear BRCA1 expression ... [CONCLUSION] BRCA1 nuclear ... of BRCA1 nuclear ... in breast cancer and ... that BRCA1 expression ... Altered BRCA1 phenotype ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10064388

Immunolocalization of BRCA1 protein in normal breast tissue and sporadic invasive ductal carcinomas: a correlation with other biological parameters.
Source

Histopathology (February 1999)

Abstract

[AIM] BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified. [METHODS AND RESULTS] The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n=108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P<0.025) and bcl-2-negative tumours (P<0.05) and frequently in ER-negative tumours. [CONCLUSION] BRCA1 nuclear expression could be considered to represent the normal or physiological phenotype. Complete loss of BRCA1 nuclear expression in breast cancer and its correlation with other poor prognostic markers suggest that BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCA1 phenotype may therefore provide an additional prognostic parameter for breast cancer.

PMID: 10065429
[Mutations in the BRCA1 gene in young Spanish women with breast cancer].
... the BRCA1 gene ... early-onset breast cancer have ... of BRCA1 mutations. ... of BRCA1 mutations ... with breast cancer diagnosed ... of BRCA1 gene ... germline BRCA1 mutations ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10065429

[Mutations in the BRCA1 gene in young Spanish women with breast cancer].
Source

Medicina clínica (1/23/1999)

Abstract

[BACKGROUND] Germline mutations in the BRCA1 gene have been associated with familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutations. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years. [PATIENTS AND METHODS] We analyzed genomic DNA samples of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cases with mutations described in the literature were screened. Analysis involved polymerase chain reaction (PCR), single-strand conformation polymorphisms (SSCP) and direct sequencing. [RESULTS] Three germline BRCA1 mutations were identified, one of them not previously described. Two mutations were found in women with familial history of breast cancer. Five additional rare variants and polymorphisms were also detected. [CONCLUSIONS] The absence of recurrent mutations or mutations detected in other countries, except for the 185delAG mutation, present in Ashkenazim population, shows the influence of ethnic and geographic origin of population studied, and illustrates the difficulties of establishing DNA-based screening tests for hereditary breast cancer.

PMID: 10070866
Identification of a C/G polymorphism in the promoter region of the BRCA1 gene and its use as a marker for rapid detection of promoter deletions.
... of BRCA1 has ... within BRCA1 . ... familial breast cancer were ... of BRCA1 are ... the BRCA1 promoter ... of BRCA1 in ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10070866

Identification of a C/G polymorphism in the promoter region of the BRCA1 gene and its use as a marker for rapid detection of promoter deletions.
Source

British journal of cancer (February 1999)

Abstract

Reduced expression of BRCA1 has been implicated in sporadic breast cancer, although the mechanisms underlying this phenomenon remain unclear. To determine whether regulatory mutations could account for the reduced expression, we screened the promoter region by sequencing in 20 patients with sporadic disease. No mutations were detected; however, a new polymorphism consisting of a C-to-G base change within the beta-promoter was identified, with the frequency of the G allele being 0.34. Close to complete linkage disequilibrium was found between this marker and the Pro871 Leu polymorphism, situated in exon 11, which has previously been shown not to be associated with breast or ovarian cancer. This indicates that the C/G polymorphism is also unlikely to play a role in either disease. However, the strength of linkage disequilibrium between these markers permitted their use for rapid screening for genomic deletions within BRCA1. A series of 214 cases with familial breast cancer were analysed using this approach; 88/214 were heterozygous for the promoter polymorphism, thereby excluding a deletion in this region. Among the remaining patients, one hemizygous case reflecting a promoter deletion was successfully identified. Therefore, this study indicates that deletions within the beta-promoter region of BRCA1 are an uncommon event in familial breast cancer. Furthermore, it suggests that mutations within the BRCA1 promoter are unlikely to account for the reported decreased expression of BRCA1 in sporadic disease.

PMID: 10070948
Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of BRCA1 mutations.
... of BRCA1 gene ... a BRCA1 mutation. ... from BRCA1 mutation ... of BRCA1 mutations. ... of BRCA1 mutations ... from BRCA1 mutation ... of BRCA1 mutations ... of BRCA1 mutation-associated ... between BRCA1 mutation-associated hereditary breast cancers and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10070948

Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of BRCA1 mutations.
Source

Journal of the National Cancer Institute (3/3/1999)

Abstract

[BACKGROUND] Breast carcinomas occurring in carriers of BRCA1 gene mutations may have a distinctly different pathway of molecular pathogenesis from those occurring in noncarriers. Data from murine models implicate loss of p53 (also known as TP53) gene function as a critical early event in the malignant transformation of cells with a BRCA1 mutation. Therefore, breast tumors from BRCA1 mutation carriers might be expected to exhibit a high frequency of p53 mutations. This study examined the frequency of p53 mutations in the breast tumors of Ashkenazi Jewish carriers and noncarriers of BRCA1 mutations. [METHODS] Tumor DNA from carriers and noncarriers of BRCA1 mutations was screened for mutations in exons 4 through 10 of the p53 gene by use of the polymerase chain reaction and single-strand conformation polymorphism (SSCP) analysis of the amplified DNA. Direct sequencing was performed on gene fragments that showed altered mobility in SSCP analysis. [RESULTS] Mutations in the p53 gene were detected in 10 of 13 tumors from BRCA1 mutation carriers versus 10 of 33 tumors from non-carriers (two-sided P = .007). The p53 mutations were distributed throughout exons 4 through 10 and included both protein-truncating and missense mutations in both groups. [CONCLUSIONS] A statistically significantly higher frequency of p53 mutations was found in breast tumors from carriers of BRCA1 mutations than from noncarriers, which adds to the accumulating evidence that loss of p53 function is an important step in the molecular pathogenesis of BRCA1 mutation-associated breast tumors. This finding may have implications for understanding phenotypic differences and potential prognostic differences between BRCA1 mutation-associated hereditary breast cancers and sporadic cancers.

PMID: 10070953
High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history.
... of BRCA1 and ... male breast cancer in ... male breast cancer mortality ... male breast cancer patients ... both BRCA1 and ... germ-line BRCA1 mutation ... male breast cancer cases ... male breast cancer in ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10070953

High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history.
Source

Cancer research (3/1/1999)

Abstract

To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of male breast cancer in Hungary, the country with the highest male breast cancer mortality rates in continental Europe, a series of 18 male breast cancer patients and three patients with gynecomastia was analyzed for germ-line mutations in both BRCA1 and BRCA2. Although no germ-line BRCA1 mutation was observed, 6 of the 18 male breast cancer cases (33%) carried truncating mutations in the BRCA2 gene. Unexpectedly, none of them reported a family history for breast/ovarian cancer. Four of six truncating mutations were novel, and two mutations were recurrent. Four patients (22%) had a family history of breast/ovarian cancer in at least one first- or second-degree relative; however, no BRCA2 mutation was identified among them. No mutation was identified in either of the genes in the gynecomastias. These results provide evidence for a strong genetic component of male breast cancer in Hungary.

PMID: 10076029
A novel small protein associated with a conjugated trienoic chromophore from membranes of scallop adductor muscle: phosphorylation by protein kinase A.
... human breast cancer susceptibility gene BRCA 1 , ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10076029

A novel small protein associated with a conjugated trienoic chromophore from membranes of scallop adductor muscle: phosphorylation by protein kinase A.
Source

Biochimica et biophysica acta (2/4/1999)

Abstract

Membranes enriched in sarcolemma from the cross-striated adductor muscle of the deep sea scallop have been found to contain a previously undescribed small protein of 6-8 kDa that can be released by treatment with organic solvent mixtures. This proteolipid co-purified with a non-amino acid chromophore containing a conjugated trienoic moiety. Although common in plants and algae, such a stable conjugated trienoic group is unusual for an animal cell. The N-terminal amino acid sequence of the protein was XEFQHGLFGXF/ADNIGLQ, which most strongly resembles sequences in the triacyl glycerol lipase precursor and the product of the human breast cancer susceptibility gene BRCA 1, but does not show similarity to previously described proteolipids. The protein was found to be one of the major substrates in its parent membrane for the catalytic subunit of protein kinase A, which may imply a regulatory function for this molecule.

PMID: 10076219
BRCA1 gene testing for breast and ovarian cancer in one family.
Most breast cancer is ... of breast cancer as ... the BRCA1 gene, ... all breast cancer and ... of BRCA1 gene ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10076219

BRCA1 gene testing for breast and ovarian cancer in one family.
Source

British journal of nursing (Mark Allen Publishing; 0)

Abstract

Most breast cancer is multifactorial in origin, but dominantly inherited genes are implicated in the development of approximately 5-10% of breast cancer as a whole. The identification of the BRCA1 gene, thought to account for 2% of all breast cancer and be present in almost all families affected by breast and ovarian cancer, makes testing for susceptibility to breast and ovarian cancer possible for the few families in which researchers have identified a gene mutation. Genetic counselling, by medically qualified geneticists, is available for people with rare genetic conditions caused by gene mutations. In this article, the authors describe their first experience of BRCA1 gene testing in 23 family members. They identify a unique role within a new specialty, cancer genetics, for specialist nurse practitioners in genetic testing and counselling.

PMID: 10080590
Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2.
... specific BRCA1 /2 ... for breast cancer and ... reduce breast cancer risk ... prevalence of B RCA1/2 ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10080590

Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2.
Source

Journal of clinical oncology : official journal of the American Society of Clinical Oncology (February 1999)

Abstract

[PURPOSE] To determine the survival benefit and cost-effectiveness of screening Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. [METHODS] We used a Markov model and Monte Carlo analysis to estimate the survival benefit and cost-effectiveness of screening for three specific mutations in a population in which their prevalence is 2.5% and the associated cancer risks are 56% for breast cancer and 16% for ovarian cancer. We assumed that the sensitivity and specificity of the test were 98% and 99%, respectively, that bilateral prophylactic oophorectomy would reduce ovarian cancer risk by 45%, and that bilateral prophylactic mastectomy would reduce breast cancer risk by 90%. We used Medicare payment data for treatment costs and Surveillance, Epidemiology, and End Results data for cancer survival. [RESULTS] Our model suggests that genetic screening of this population could prolong average nondiscounted survival by 38 days (95% probability interval, 22 to 57 days) for combined surgery, 33 days (95% probability interval, 18 to 43 days) for mastectomy, 11 days (95% probability interval, 4 to 25 days) for oophorectomy, and 6 days (95% probability interval, 3 to 8 days) for surveillance. The respective cost-effectiveness ratios per life-year saved, with a discount rate of 3%, are $20,717, $29,970, $72,780, and $134,273. [CONCLUSION] In this Ashkenazi Jewish population, with a high prevalence of BRCA1/2 mutations, genetic screening may significantly increase average survival and, depending on costs and screening/treatment strategies, may be cost-effective by the standards of accepted cancer screening tests. According to our model, screening is cost-effective only if all women who test positive undergo prophylactic surgery. These estimates require confirmation through prospective observational studies and clinical trials.

PMID: 10085126
Positive regulation of the BRCA1 promoter.
... the BRCA1 gene, ... of BRCA1 gene ... the BRCA1 transcriptional ... of BRCA1 transcription. ... normal BRCA1 transcription ... to breast cancer susceptibility.   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10085126

Positive regulation of the BRCA1 promoter.
Source

The Journal of biological chemistry (3/26/1999)

Abstract

Inherited mutations in the BRCA1 gene, presumably leading to loss of function, confer susceptibility to breast and ovarian neoplasms and are thought to be responsible for approximately 2.5-5% of all breast cancers. It has been suggested that alternative mechanisms, such as disruption of transcription, may also be involved in the suppression of BRCA1 gene expression/function in breast cancers. Therefore, we initiated studies on the BRCA1 transcriptional promoter. Utilizing systematic promoter deletions and transient transfection assays, a 36-base pair region was determined to be important for the positive regulation of BRCA1 transcription. Deletion of this positive regulatory region resulted in a significant loss of promoter activity. Utilizing DNA binding assays, proteins with specific affinities for the positive regulatory region were detected. Disruption of the DNA-protein complexes could affect normal BRCA1 transcription and may contribute to breast cancer susceptibility.

PMID: 10090482
Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease. Mutations in brief no. 224. Online.
... the BRCA1 and ... with breast cancer before ... for BRCA1 exon ... of BRCA1 and ... of BRCA1 , ... the BRCA1 or ... the BRCA1 gene: ... ( BRCA1 ) ... of BRCA1 published ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10090482

Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease. Mutations in brief no. 224. Online.
Source

Human mutation (1999)

Abstract

Since the identification of the BRCA1 and BRCA2 genes (MIM#s 113705 and 600185), more than hundred different mutations throughout both genes have been reported. Recurrent mutations are rare and mainly due to founder effects. We analyzed 12 sporadic female patients with breast cancer before age 35, as well as 16 unrelated families, presenting with either (i) at least 3 first degree relatives with breast and/or ovarian cancer diagnosed at any age, or (ii) at least 2 first and/or second degree relatives with breast and/or ovarian cancer before age 45 years. We performed a protein truncation test for BRCA1 exon 11 and BRCA2 exons 10 and 11 and heteroduplex analysis for all the remaining exons of BRCA1 and 2. Presence of genomic deletions encompassing exons 13 or 22 of BRCA1, known to be Dutch founder mutations, was investigated by PCR. In 6/16 (37.5%) unrelated families the causal mutation in either the BRCA1 or BRCA2 gene was identified. Four different mutations were found in the BRCA1 gene: IVS5+3A>G (intron 5), 1191delC (exon 11), R1443X (exon 13), IVS22+5G>A (intron 22) and two in the BRCA2 gene: 6503delTT (exon 11), 6831delTG (exon 11). 1191delC ( BRCA1) and 6831delTG (BRCA2) are novel mutations. IVS5+3A>G in exon 5 of BRCA1 published by Peelen et al. (1997) as a novel Belgian mutation, was identified in one additional family, not fulfilling our inclusion criteria. In the group of 12 sporadic female patients no mutations were found.

PMID: 10090719
Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1.
... the breast cancer protein BRCA1 alters ... in BRCA1 that ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10090719

Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1.
Source

Genes & development (3/15/1999)

Abstract

An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predisposing mutations in BRCA1 that abolish transcriptional activation also prevent chromatin remodeling and activation of replication. Chromatin remodeling occurs even in the absence of a functional replication origin. Thus, increasing chromatin accessibility may be an important mechanism used by transcription factors to facilitate multiple nuclear processes.

PMID: 10090881
The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews.
... genes BRCA1 and ... in BRCA1 and ... of breast cancer in ... of breast cancer before ... for BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10090881

The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews.
Source

American journal of human genetics (April 1999)

Abstract

Three founder mutations in the cancer-associated genes BRCA1 and BRCA2 occur frequently enough among Ashkenazi Jews to warrant consideration of genetic testing outside the setting of high-risk families with multiple cases of breast or ovarian cancer. We estimated the prevalence of these founder mutations in BRCA1 and BRCA2 in the general population of Ashkenazi Jews according to age at testing, personal cancer history, and family cancer history. We compared the results of anonymous genetic testing of blood samples obtained in a survey of >5,000 Jewish participants from the Washington, DC, area with personal and family cancer histories obtained from questionnaires completed by the participants. In all subgroups defined by age and cancer history, fewer mutations were found in this community sample than in clinical series studied to date. For example, 11 (10%) of 109 Jewish women who had been given a diagnosis of breast cancer in their forties carried one of the mutations. The most important predictor of mutation status was a previous diagnosis of breast or ovarian cancer. In men and in women never given a diagnosis of cancer, family history of breast cancer before age 50 years was the strongest predictor. As interest in genetic testing for BRCA1 and BRCA2 in the Jewish community broadens, community-based estimates such as these help guide those seeking and those offering such testing. Even with accurate estimates of the likelihood of carrying a mutation and the likelihood of developing cancer if a mutation is detected, the most vexing clinical problems remain.

PMID: 10092133
Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers.
Sporadic breast cancers often ... the BRCA1 gene ... the BRCA1 gene ... that BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10092133

Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers.
Source

Genes, chromosomes & cancer (April 1999)

Abstract

Sporadic breast cancers often show allelic losses on the long arm of chromosome 17. Since the BRCA1 gene lies at 17q21.1 and the TOC locus, associated with esophageal cancer, lies at 17q25.1, either gene could be the target of those losses. We examined both loci in 178 primary breast cancers, using microsatellite markers covering the relevant regions of 17q, and observed allelic losses in 97 tumors (55%). Losses were most frequent at markers around the TOC locus (48% at D7S1839 and 43% at D17S1603), where we identified a distinct commonly deleted region within a I -cM interval. Another larger, separate commonly deleted region including the BRCA1 gene was also identified, which exhibited 45% of allelic loss (at D17S934). Allelic loss on 17q was more frequent in tumors of the solid-tubular histologic type (P = 0.0129) and in estrogen-negative and progesterone-negative tumors (P = 0.0281 and 0.0196, respectively). The results indicated that BRCA1 and TOC are independent targets of allelic loss on 17q in primary breast cancers, and that inactivation of the TOC locus in particular may play an important role in the genesis of sporadic breast tumors.

PMID: 10098775
Prevalence of BRCA1 and BRCA2 Jewish mutations in Spanish breast cancer patients.
... ( BRCA1 ) ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10098775

Prevalence of BRCA1 and BRCA2 Jewish mutations in Spanish breast cancer patients.
Source

British journal of cancer (March 1999)

Abstract

We screened the 185delAG and 5382insC ( BRCA1) and the 6174delT (BRCA2) mutation in 298 Spanish women with breast cancer. Two women (one with Sephardic ancestors) presented the 185delAG mutation and the same haplotype reported in Ashkenazim with this mutation. This suggests a common origin of the 185delAG in both Sephardic and Ashkenazi populations.

PMID: 10161380
Genetic developments in breast cancer.
... to BRCA1 because ... this breast cancer susceptibility ... hereditary breast cancer (10 ... sporadic breast cancer (which ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10161380

Genetic developments in breast cancer.
Source

Journal of insurance medicine (New York, N.Y.; 0)

Abstract

In this paper I have reviewed the current literature on the genetic mutations found in association with breast cancer. More emphasis has been given to BRCA1 because of the excitement generated with the cloning of this breast cancer susceptibility gene. A number of somatic mutations have been described (loss of heterozygosity, overexpression, and other mutations) in breast cancers. While strides have been made in unraveling the genetic basis of hereditary breast cancer (10 to 15 percent of all breast cancers), the genetic causes of most sporadic breast cancer (which comprise 85 to 90 percent) have yet to be discovered but they are likely the result of a step wise progression of cumulative genetic events, similar to those seen in colon cancer.

PMID: 10188308
[Epidemiology of breast cancer].
Breast cancer is ... of breast cancer (OR ... ( Brca1 , ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10188308

[Epidemiology of breast cancer].
Source

Bulletin de l'Académie nationale de médecine (1998)

Abstract

Breast cancer is the predominant cancer among women in France, accounting for about 32% of all new cases. Increasing incidence rates are reported by the regional registries, while the national mortality rates seem to reach a plateau particularly in the women under 65 years old. During the last 20 years the survival of patients with positive nodes has been increased. Nulliparity and increasing age at first birth are well established risk factors as well as age at menarche and age at menopause (OR approximately equal to 2). The role of other risk factors such as hormone replacement therapy, oral contraception, lactation remain controversial (OR approximately equal to 1-1.5). Total calories consumption, obesity after menopause, and alcohol are possible risk factors (OR approximately equal to 2-3). Previous irradiation of thorax, proliferative benign mastopathy are increasing the risk of breast cancer (OR approximately equal to 3-5). Consumption of fruits and vegetables, as well as physical exercise could decrease the risk (OR approximately equal to 0.6). There is a strong heredity component for about 10-15% of the cases. Approximately in half of these cases a mutated gene ( Brca1, Brca2 ...) have been identified.

PMID: 10188893
Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2.
... in BRCA1 or ... of BRCA1 and ... in BRCA1 . ... bilateral breast cancer case ... unilateral breast cancer case ... a BRCA1 or ... of breast cancer diagnosed ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10188893

Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2.
Source

British journal of cancer (March 1999)

Abstract

For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays. In 31 of the 104 families tested, mutations were detected (30%). The majority of these mutations (25) occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with both breast and ovarian cancer and in 16 out of 79 families (20%) with exclusively cases of breast cancer. Thus, an ovarian cancer case strongly predicted finding a mutation (P < 0.001). Within the group of small breast-cancer-only families, a bilateral breast cancer case or a unilateral breast cancer case diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation (P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian cancer families with at least one case of ovarian cancer, bilateral breast cancer, or a case of breast cancer diagnosed before age 40, should be referred for mutation screening.

PMID: 10189988
[Impact of recent oncogenetic progress on the management of high risk breast cancer patients: the example of BRCA1 and BRCA2 genes].
... hereditary breast cancers and ... histories. BRCA1 -associated breast cancers appear ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10189988

[Impact of recent oncogenetic progress on the management of high risk breast cancer patients: the example of BRCA1 and BRCA2 genes].
Source

Annales d'endocrinologie (1998)

Abstract

Evidence is mounting that hereditary breast cancers and sporadic cases harbor distinct clinical and morphological patterns that are thought to be linked to different natural histories. BRCA1-associated breast cancers appear as high grade, poorly differentiated, highly proliferating, and frequently estrogen receptor negative tumors. Surprisingly, despite these features usually associated with a poor outlook, no decrease in the overall survival is observed in hereditary cases. These elements may be of valuable help in the design of strategies in the medical management of cancer prone individuals.

PMID: 10193517
BRCA1 and BRCA2 proteins: roles in health and disease.
... all breast cancer is ... genes: BRCA1 and ... the BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10193517

BRCA1 and BRCA2 proteins: roles in health and disease.
Source

Molecular pathology : MP (October 1998)

Abstract

Between 5% and 10% of all breast cancer is hereditary, with patients having a strong family history of the disease. The remaining 90-95% of cases are classed as sporadic. Within the inherited group, 80-90% of cases are the result of germline mutations affecting two recently identified genes: BRCA1 and BRCA2. Since the sequencing of these genes, considerable research on the genetics of the mutation carriers has been performed, with less attention having been focused on the BRCA1 and BRCA2 proteins themselves. The structure and function of the protein products thus continues to hold mystery and might be the key to the full understanding of this complex disease.

PMID: 10195418
The functions of breast cancer susceptibility gene 1 ( BRCA1) product and its associated proteins.
... familial breast cancer cases ... the breast cancer susceptibility ... ( BRCA1 ). ... of BRCA1 mutations ... and BRCA1 -associated ... of BRCA1 has ... Wild-type BRCA1 protein ... c-myc, BRCA1 -associated ... of BRCA1 in ... Overall, BRCA1 protein ... in BRCA1 may ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10195418

The functions of breast cancer susceptibility gene 1 ( BRCA1) product and its associated proteins.
Source

Biological chemistry (February 1999)

Abstract

About half of the familial breast cancer cases are found to bear mutations in the breast cancer susceptibility gene 1 ( BRCA1). The majority of BRCA1 mutations produce a truncated protein and BRCA1-associated breast tumors exhibit a number of defined tumor phenotypes. The function of BRCA1 has been examined in gene knockout mice in which the nullizygous mice die early in utero, but this lethality can be partially rescued by a nullizygous p53 mutation. Wild-type BRCA1 protein binds to a number of cellular proteins, including DNA repair protein Rad51, tumor suppressor p53, RNA polymerase II holoenzyme, RNA helicase A, CtBP-interacting protein, c-myc, BRCA1-associated RING domain protein (BARD1), BRCA2 protein, etc. These proteins likely mediate the involvement of BRCA1 in DNA repair, transcriptional transactivation, and cell cycle control. Overall, BRCA1 protein may act as a converging vehicle for cell regulatory proteins to associate with. Therefore, mutations in BRCA1 may affect the composition of these complexes on which dysregulation of cellular functions with eventual development of malignancy is expected.

PMID: 10196379
Germline BRCA1 alterations in a population-based series of ovarian cancer cases.
... of breast cancer susceptibility ... ( BRCA1 ) ... of BRCA1 alterations ... reporting BRCA1 alterations ... for BRCA1 alterations ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10196379

Germline BRCA1 alterations in a population-based series of ovarian cancer cases.
Source

Human molecular genetics (May 1999)

Abstract

The objective of this study was to provide more accurate frequency estimates of breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian cancer cases. This is the first population-based ovarian cancer study reporting BRCA1 alterations derived from a comprehensive screen of the entire coding region. One hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using the RNase mismatch cleavage assay followed by direct sequencing. Two truncating mutations, 962del4 and 3600del11, were identified. Both patients had a family history of breast or ovarian cancer. Several novel as well as previously reported uncharacterized variants were also identified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Caucasian cancer cases in this series and 24 sister controls using allele-specific amplification. The rare form of the Q356R polymorphism was significantly ( P = 0.03) associated with a family history of ovarian cancer, suggesting that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of polymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population.

PMID: 10197592
BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.
... hereditary breast cancer susceptibility genes, BRCA1 and ... that BRCA1 and ... Thus, BRCA1 and ... The BRCA1 /BRCA2 ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10197592

BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.
Source

Cancer research (4/1/1999)

Abstract

The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian cancer and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51. We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells. Thus, BRCA1 and BRCA2 participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function in postreplicational repair processes activated during the DNA synthesis stage of the cell cycle.

PMID: 10197594
Mammary gland development, reproductive history, and breast cancer risk.
... for breast cancer that ... alter breast cancer risk ... genes, BRCA1 and ... influence breast cancer risk.   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10197594

Mammary gland development, reproductive history, and breast cancer risk.
Source

Cancer research (4/1/1999)

Abstract

The observation that normal pathways of differentiation and development are invariably altered during the process of carcinogenesis implies an intrinsic relationship between these processes. This relationship is particularly evident in the breast, as exemplified by the existence of endocrine risk factors for breast cancer that are related to the timing of normal developmental events. Understanding the mechanisms by which normal developmental events alter breast cancer risk is a central focus of our laboratory. Herein, we describe three approaches being taken in our laboratory toward defining the molecular basis of this relationship. These include: determining the roles played by the tumor suppressor genes, BRCA1 and BRCA2, in the normal differentiation and development of the breast; studying the function of three novel protein kinases identified in our laboratory in mammary epithelial development; and defining the molecular and cellular changes that occur in the breast as a result of reproductive events known to influence breast cancer risk.

PMID: 10204401
[Hereditary neoplastic diseases (genetic predisposition and cancer syndromes)].
... in BRCA1 and ... of BRCA1 gene ... the Breast Cancer Linkage ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10204401

[Hereditary neoplastic diseases (genetic predisposition and cancer syndromes)].
Source

Orvosi hetilap (2/28/1999)

Abstract

After one decade of molecular genetic studies, little doubt remains that cancer is a genetic disease. While mutations in somatic cells may cause cancer, they don't carry forward to the next generation. In fact, most cancers arise in this way. In some individuals mutations in cancer related genes may be present at the constitutional level, inherited from one of the parents. An individual who carries a mutant allele of an inherited cancer gene has a variable risk of cancer that is influenced by other genetic and non-genetic factors (such as other cellular genes, dietary, lifestyle, and environmental factors). Collectively, the syndromes affect about 1% of cancer patients. During the past decade about 25 different cancer susceptibility genes have been reported to be linked to the known hereditary cancer syndromes. Over the period of the last three to five years, studies of the specific mutations responsible for these syndromes and the cellular signaling pathways disrupted by the mutant proteins have begun to provide unprecedented insights into the molecular origin and pathogenesis of inherited and sporadic forms of cancer. This article reviews the cancer susceptibility genes and cancer syndromes, particularly those associated with common malignancies (breast, prostate and colorectal carcinomas). Results of the mutation analysis in BRCA1 and BRCA2 genes of Hungarian breast/ovarian cancer families will be briefly discussed. These data indicate a strong founder effect for some mutations of BRCA1 gene in Hungary. As a results of recent publicity of discoveries of molecular genetics--particularly those related to common malignancies--due to publicity in the scientific and the lay press awareness and demand for predictive DNA tests have dramatically increased worldwide over the past 3 years. The author, as a member of the Breast Cancer Linkage Consortium, shares the consensus view that genetic testing and genetic counseling for cancer risk together with surveillance and management should for the present be offered only through specialist clinical genetic departments as part of a research evaluation.

PMID: 10205268
Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat.
... the BRCA1 gene ... of breast cancer among BRCA1 mutation ... the BRCA1 -associated age-specific breast cancer risk. ... germline BRCA1 mutations, ... of breast cancer if ... at breast cancer diagnosis ... among BRCA1 mutation ... of BRCA1 -associated ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10205268

Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat.
Source

American journal of human genetics (May 1999)

Abstract

Compared with the general population, women who have inherited a germline mutation in the BRCA1 gene have a greatly increased risk of developing breast cancer. However, there is also substantial interindividual variability in the occurrence of breast cancer among BRCA1 mutation carriers. We hypothesize that other genes, particularly those involved in endocrine signaling, may modify the BRCA1-associated age-specific breast cancer risk. We studied the effect of the CAG repeat-length polymorphism found in exon 1 of the androgen-receptor (AR) gene (AR-CAG). AR alleles containing longer CAG repeat lengths are associated with a decreased ability to activate androgen-responsive genes. Using a sample of women who inherited germline BRCA1 mutations, we compared AR-CAG repeat length in 165 women with and 139 women without breast cancer. We found that women were at significantly increased risk of breast cancer if they carried at least one AR allele with >/=28 CAG repeats. Women who carried an AR-CAG allele of >/=28, >/=29, or >/=30 repeats were given a diagnosis 0.8, 1.8, or 6.3 years earlier than women who did not carry at least one such allele. All 11 women in our sample who carried at least one AR-CAG allele with >/=29 repeats had breast cancer. Our results support the hypothesis that age at breast cancer diagnosis is earlier among BRCA1 mutation carriers who carry very long AR-CAG repeats. These results suggest that pathways involving androgen signaling may affect the risk of BRCA1-associated breast cancer.

PMID: 10207643
Participation in breast cancer susceptibility testing protocols: influence of recruitment source, altruism, and family involvement on women's decisions.
... family-based BRCA1 /2 ... of breast cancer and ... on BRCA1 /2 ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10207643

Participation in breast cancer susceptibility testing protocols: influence of recruitment source, altruism, and family involvement on women's decisions.
Source

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (April 1999)

Abstract

[OBJECTIVES] We offered education, counseling, and family-based BRCA1/2 testing to women at increased risk of breast cancer and assessed (a) their reasons for participating and (b) whether source of recruitment, desire to help research (altruism), and the need to communicate with their affected relative about testing distinguish those who did and those who did not complete each phase of our protocol. [MATERIALS AND METHODS] We sent invitations to 403 women who had completed a questionnaire on BRCA1/2 testing, 178 of whom were considered high risk because they had more than one relative on the same side of the family with early-onset breast cancer. [RESULTS] Among the 132 high-risk respondents from the mid-Atlantic states (where testing was offered), 36% (n = 47) were interested in counseling. Those who actually attended counseling were more likely to have some college education, a higher perceived risk of breast cancer, and a greater fear of stigma and were less likely to have a daughter than those who did not attend. The reasons for attending that were rated "very important" were to learn about the test (80%), to have the test (43%), and to help research (38%). High-risk women were eligible for testing only if their affected relative was willing to be tested and tested positive. After the session, 83% intended to ask their affected relative to be tested, but only half of the affected relatives actually came for pretest counseling. The proportion of participants who ultimately involved an affected relative was 2.5 times higher among women from a clinical population (25%) than among those from a registry population (10%); in this latter population, an altruistic desire to help research was a greater motivator for participation than interest in being tested. [CONCLUSIONS] Source of recruitment influences both motivations to attend education and counseling and actual testing behavior. These results have implications for interpretation of findings from studies in research settings as well as for informed consent and decision-making in the context of family-based testing.

PMID: 10208417
Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics.
... of BRCA1 has ... the BRCA1 promoter ... of breast cancer cases ... the BRCA1 promoter ... the BRCA1 promoter ... of BRCA1 that ... the BRCA1 promoter ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10208417

Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics.
Source

Oncogene (3/18/1999)

Abstract

Reduced expression of BRCA1 has been reported in sporadic breast cancer, although the mechanisms underlying this phenomenon remain unclear. Abnormal methylation leading to silencing of tumour suppressor genes has been implicated in tumorigenesis in a wide range of sporadic cancers. Therefore, we sought to determine the frequency of methylation within the BRCA1 promoter region in a large group of sporadic invasive breast (n =96) and ovarian (n = 43) carcinomas using Southern analyses. Overall, methylation was detected in 11% of breast cancer cases and in 5% of ovarian tumours. Methylation of the BRCA1 promoter region was strongly correlated with lack of estrogen and progesterone receptor expression. It is clear from the frequency of abnormal methylation of the BRCA1 promoter region, that this cannot be the sole mechanism mediating the reduced expression of BRCA1 that has previously been reported to occur in the majority of invasive sporadic breast tumours. Nevertheless this study suggests that abnormal methylation of the BRCA1 promoter may be important in tumorigenesis in a subset of sporadic breast and ovarian cancers.

PMID: 10210766
[Inserm ad hoc committee: Recommendations for the management of women with a genetic risk for developing cancer of the breast and/or the ovary].
... to BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10210766

[Inserm ad hoc committee: Recommendations for the management of women with a genetic risk for developing cancer of the breast and/or the ovary].
Source

Bulletin du cancer (March 1999)

Abstract

[BACKGROUND] Almost 10% of breast and ovarian cancer are inherited, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite the uncertainty, consensus guidelines were defined to assist practitioners', and patients' decisions about the health care decisions to be made. [METHODOLOGY] The ad hoc committee consisted of 14 experts designated by the French National Institute for Health and Medical Research. They all attended eleven workshops at which a systematic analytical review of more than 3,500 articles was carried out. Five additional experts critically analyzed the first version of the report. Process: Two thresholds were defined on a probability scale giving the risk of developing breast or ovarian cancer, to serve as a means of deciding as whether an intervention is worthwhile. The first threshold is that above which an intervention can be envisaged or recommended; the second is that under which an intervention can be ruled out; between the two, the decision has to be made on a each by case basis. SCREENING AND PREVENTIVE STRATEGIES ANALYZED: About breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. [MAIN CONCLUSIONS] With each strategy the following points were dealt with: the information to be delivered to the consult and, the procedure and the indications. The committee's opinion about BRCA mutation screening is that population-based or even large scale implementation are not justified. The committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and involvement in clinical trials.

PMID: 10213514
Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study.
Breast cancers arising ... the BRCA1 or ... with breast cancer diagnosed ... by BRCA1 and ... factors. Breast cancers occurring in BRCA1 mutation ... in BRCA1 mutation ... early-onset breast cancers within ... from BRCA1 mutation ... a BRCA1 breast cancer phenotype ... contrast, breast cancers arising ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10213514

Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study.
Source

Cancer research (4/15/1999)

Abstract

Breast cancers arising in women with and without a germline mutation in the BRCA1 or BRCA2 gene display different histological features, which suggests unique mechanisms of molecular pathogenesis: We used a molecular pathological analysis to define the genetic abnormalities relevant to these specific pathogeneses. Tumor material was studied from 40 women with breast cancer diagnosed before 40 years of age, sampled from a population-based study and stratified by BRCA1 and BRCA2 germline mutation status. Cases were not selected for family history or ethnic origin, and none were known to be genetically related. Thus, germline mutation itself is likely to impact on the molecular pathogenesis of these tumors, with no substantial influence due to modifying genetic or environmental factors. Breast cancers occurring in BRCA1 mutation carriers had significantly higher levels of p53 expression, including the preinvasive (carcinoma in situ) stage of disease, compared with cancers occurring in BRCA2 mutation carriers or women with no detectable germline mutation. These cancers also had a higher proliferation rate as measured by Ki-67 antibody. Expression of the prognostic factors c-erbB-2, cyclin D1, and estrogen receptor was significantly less common in BRCA1 mutation carriers. Lower levels of cyclin D1 were also found in cancers from BRCA2 mutation carriers compared with non-mutation carriers. Direct p53 mutation analysis revealed mutations in 18% of all of the early-onset breast cancers within the study and included rare insertion and deletional mutations in cancers from BRCA1 mutation carriers. Our data indicate that a BRCA1 breast cancer phenotype may be recognized by an exceptionally high proliferation rate and early and frequent p53 overexpression but infrequent selection for overexpression of several other prognostic factor proteins known to be involved in breast oncogenesis. In contrast, breast cancers arising in BRCA2 mutation carriers have a more heterogeneous phenotypic profile.

PMID: 10220145
Reliable and sensitive detection of premature termination mutations using a protein truncation test designed to overcome problems of nonsense-mediated mRNA instability.
... and breast cancer ( BRCA1 ). ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10220145

Reliable and sensitive detection of premature termination mutations using a protein truncation test designed to overcome problems of nonsense-mediated mRNA instability.
Source

Human mutation (1999)

Abstract

The protein truncation test (PTT) is a mutation-detection method used to scan for premature termination (nonsense) mutations. PCR amplification of the DNA or mRNA source material is performed using forward primers containing a T7-promoter sequence and translation initiation signals such that the resultant products can be transcribed and translated in vitro to identify the smaller truncated protein products. mRNA is commonly used as the source material, but success of the PTT and other RNA-based mutation detection methods can be severely compromised by nonsense mutation-induced mRNA decay, a well-documented process that is often overlooked in mutation detection strategies. In this study, we develop an RNA-based PTT that overcomes the problem of mRNA decay by preincubating cells with cycloheximide to stabilise the mutant mRNA. The effectiveness of this method for mutation detection in abundant mRNAs was demonstrated in osteogenesis imperfecta fibroblasts by the protection of type I collagen (COL1A1) mRNA containing nonsense mutations that normally resulted in mutant mRNA degradation. Stabilisation of mutant mismatch repair gene (MLH1) mRNA was also observed in transformed lymphocytes from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Importantly, our strategy also stabilised very low-level (or illegitimate) nonsense-containing transcripts in lymphoblasts from patients with Bethlem myopathy (COL6A1), familial adenomatous polyposis (APC), and breast cancer ( BRCA1). The greatly increased sensitivity and reliability of this RT-PCR/PTT protocol has broad applicability to the many genetic diseases in which only blood-derived cells may be readily available for analysis.

PMID: 10227398
High frequency of BRCA1/2 germline mutations in 42 Belgian families with a small number of symptomatic subjects.
... for BRCA1 /2 ... a BRCA1 /2 ... one breast cancer was ... the BRCA1 gene ... [CONCLUSION] BRCA1 /2 ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10227398

High frequency of BRCA1/2 germline mutations in 42 Belgian families with a small number of symptomatic subjects.
Source

Journal of medical genetics (April 1999)

Abstract

[AIM] The initial risk assessments for BRCA1/2 mutation carriers and estimates of carrier frequencies were based on extended pedigrees with a large number of symptomatic subjects. When counselling based on BRCA gene mutation analysis was initiated, we faced requests for counselling mostly from members of small families with only two or three affected members. We report on the likelihood of finding a BRCA mutation in such small families. [METHODS] In the first 100 families that came for oncogenetic counselling since September 1994, a BRCA1/2 gene mutation screen was initiated if there were two or more symptomatic first degree relatives, if one of them had ovarian cancer, or if one breast cancer was diagnosed before the age of 50 years. [RESULTS] BRCA gene mutations were found and confirmed by sequencing in 14 out of 42 families (33%); 10 mutations were in the BRCA1 gene and four in the BRCA2 gene. Our findings indicate an increased probability of detecting a BRCA gene mutation when ovarian cancer occurred in the family. There is no increased probability of detecting a mutation with increasing numbers of breast cancers. Only 22% of the eligible presymptomatic family members opted for testing. The presymptomatic female carriers currently prefer breast surveillance rather than prophylactic surgery. [CONCLUSION] BRCA1/2 gene mutation testing can be done with reasonable efficiency in the Belgian population when there are two symptomatic family members. The availability of testing does not lead to a high frequency of requests for testing by presymptomatic family members.

PMID: 10229196
Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions.
... of BRCA1 and ... of breast cancer and ... of BRCA1 - ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10229196

Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions.
Source

Oncogene (4/15/1999)

Abstract

Inheritance of germ-line mutant alleles of BRCA1 and BRCA2 confers a markedly increased risk of breast cancer and we have previously reported a higher incidence of p53 mutations in these tumours than in grade matched sporadic tumours. We have now characterized these p53 mutants. The results of these studies identify a novel class of p53 mutants previously undescribed in human cancer yet with multiple occurrences in BRCA-associated tumours which retain a profile of p53-dependent activities in terms of transactivation, growth suppression and apoptosis induction which is close or equal to wild-type. However, these mutants fail to suppress transformation and exhibit gain of function transforming activity in rat embryo fibroblasts. These mutants therefore fall into a novel category of p53 mutants which dissociate transformation suppression from other wild-type functions. The rarity of these mutants in human cancer and their multiple occurrence in BRCA-associated breast tumours suggests that these novel p53 mutants are selected during malignant progression in the unique genetic background of BRCA1- and BRCA2-associated tumours.

PMID: 10323242
Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan.
... of breast cancer were ... the BRCA1 and ... the BRCA1 gene, ... of BRCA1 mRNA ... other breast cancer families. ... both BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10323242

Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan.
Source

Human genetics (March 1999)

Abstract

A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation.

PMID: 10329379
Prolactin-dependent up-regulation of BRCA1 expression in human breast cancer cell lines.
... the BRCA1 gene ... human breast cancer cell ... in BRCA1 mRNA ... in BRCA1 mRNA ... of BRCA1 protein ... of BRCA1 protein ... whereas BRCA1 protein ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10329379

Prolactin-dependent up-regulation of BRCA1 expression in human breast cancer cell lines.
Source

Biochemical and biophysical research communications (5/10/1999)

Abstract

We report experimental evidence that BRCA1, a breast and ovarian cancer susceptibility gene, is up-regulated in response to prolactin (PRL) stimulation. Expression of the BRCA1 gene was monitored in 2 human breast cancer cell lines (MCF-7 and T-47D) and in the normal mammary epithelial cell line MCF10a. Using competitive RT-PCR, we have shown that PRL induced an increase in BRCA1 mRNA level in MCF-7 and T-47D cell lines at a dose resulting in the maximal enhancement of cell proliferation. The up-regulation was 12-fold in MCF-7 cells and 2-fold in T-47D cells. No increase in BRCA1 mRNA level was observed in the MCF10a cell line. The level of BRCA1 protein was quantified using an affinity chromatography strategy. At the protein level, PRL treatment induced a 4-fold increase of BRCA1 protein expression in MCF-7 and a 6-fold increase in T-47D cells, whereas BRCA1 protein expression was not affected by PRL in MCF10a.

PMID: 10333246
Tumor suppressor genes and breast cancer.
... most breast cancer cases ... p53, BRCA1 , ... p53, BRCA1 , ... to breast cancer risk, ... in breast cancer cells. ... of breast cancer development ... p53, BRCA1 , ... to breast cancer development, ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10333246

Tumor suppressor genes and breast cancer.
Source

Radiation oncology investigations (1999)

Abstract

The genetic determinants for most breast cancer cases remain elusive. However, a mutation in a tumor suppressor gene, such as p53, BRCA1, BRCA2, or ATM, has been determined to be one mechanism of breast carcinogenesis. It has been established that inherited mutations in p53, BRCA1, and BRCA2 significantly contribute to breast cancer risk, although the importance of an inherited ATM mutation is controversial. Sporadic mutations in p53 are also common in breast cancer cells. The precise deficiencies that result from these genetic mutations have yet to be fully described. Although the functions of these genes are different, they are all involved in the maintenance of genomic stability after DNA damage. Mutations that impair the function of these four genes may adversely affect the manner in which DNA damage is processed. It is likely that the risk of breast cancer development is increased through this mechanism. In this article, we review the relevancy of p53, BRCA1, BRCA2, and ATM mutations to breast cancer development, and review the in vitro, in vivo, and clinical data exploring the mechanisms by which these mutations affect genomic integrity and DNA damage repair.

PMID: 10334549
Moral concerns of different types of patients in clinical BRCA1/2 gene mutation testing.
... as breast cancer may ... on BRCA1 /2 ... specific BRCA1 /2 ... of BRCA1 /2 ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10334549

Moral concerns of different types of patients in clinical BRCA1/2 gene mutation testing.
Source

Journal of clinical oncology : official journal of the American Society of Clinical Oncology (May 1999)

Abstract

[PURPOSE] Implementing predictive genetic testing for a severe and common chronic disease such as breast cancer may raise unique ethical problems. Here we report on moral concerns experienced by patients in the setting of genetic counseling based on BRCA1/2 gene testing. [PATIENTS AND METHODS] Patients were members of breast or breast/ovarian cancer families in a consecutive series of 100 families who received counseling at a familial cancer clinic. The patients' moral concerns were identified using the grounded theory approach in the qualitative analysis of verbal transcripts of 45 counseling sessions. Included were sessions with patients who had breast and ovarian cancer, as well as their male and female relatives, before and after the specific BRCA1/2 gene mutation was identified in the family, and before and after those who opted for mutation analysis were informed of their carrier status. [RESULTS] There is an association of BRCA1/2 gene mutation carrier status and specific topics of moral concern. The moral preoccupations of patients with breast and ovarian cancer (probable carriers) related to their being instrumental in the detection of the specific mutation segregating in the family. The preoccupations of possible carriers concerned their own offspring. Individuals who tested positive (proven carriers) were concerned with issues of confidentiality. Patients who tested negative (proven noncarriers) were concerned with helping siblings and other relatives. [CONCLUSION] Knowledge of the moral concerns of subjects in the study sample may help health care providers be aware of the moral concerns of their own patients. This report may also contribute to the debate on predictive testing for familial adult-onset diseases from the patient's perspective.

PMID: 10334989
BRCA1 inhibition of estrogen receptor signaling in transfected cells.
... the breast cancer susceptibility gene BRCA1 confer ... assays, BRCA1 was ... wild-type BRCA1 suppresses ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10334989

BRCA1 inhibition of estrogen receptor signaling in transfected cells.
Source

Science (New York, N.Y.; 5/21/1999)

Abstract

Mutations of the breast cancer susceptibility gene BRCA1 confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-alpha) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-alpha. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.

PMID: 10337719
Prognostic implications of cancer susceptibility genes: any news?
... Familial breast cancer can ... the breast cancer susceptibility gene BRCA 1 , ... neither BRCA 1 nor ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10337719

Prognostic implications of cancer susceptibility genes: any news?
Source

Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer (1999)

Abstract

Recent advances in our understanding of the genetic basis of several inherited predispositions to cancer have raised the possibility that there may be differences in prognosis between patients harbouring genetic susceptibilities to cancer and persons presenting with sporadic disease. The two best studied models of inherited susceptibilities to cancer will be considered, those of colorectal cancer and familial breast cancer. Familial colorectal cancer can be subdivided into essentially two groups: familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Familial breast cancer can be subdivided into three groups: those that can be accounted for by mutations in the breast cancer susceptibility gene BRCA 1, families harbouring mutations in BRCA 2 and families where neither BRCA 1 nor BRCA 2 appear to be involved. In this chapter several aspects of these inherited cancer predispositions will be discussed and compared with their equivalent sporadic disease counterparts.

PMID: 10343884
BRCA1 and BRCA2 gene mutations and risk of breast cancer. Public health perspectives.
CONTENT: Breast cancer is ... the BRCA1 gene, ... second breast cancer gene, ... of BRCA1 gene ... specific BRCA1 allele, ... for breast cancer susceptibility, ... for breast cancer are ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10343884

BRCA1 and BRCA2 gene mutations and risk of breast cancer. Public health perspectives.
Source

American journal of preventive medicine (February 1999)

Abstract

CONTENT: Breast cancer is the most common cancer and the second most common cause of cancer death among U.S. women. In 1998, about 178,700 new cases will be diagnosed and 43,500 women will die from the disease. Mutations in the BRCA1 gene, which was cloned in 1994 and is located on chromosome 17q, have been identified as causes of predisposition to breast, ovarian, and other cancers. A second breast cancer gene, BRCA2, has been localized to chromosome 13q. Using inferential procedures, the overall carrier frequency of BRCA1 gene mutations has been estimated at 1 in 500 in the general U.S. population. Recent studies have indicated that the carrier frequency of a specific BRCA1 allele, the 185delAG mutation, may be as high as 0.8% to 1% among women of Ashkenazi Jewish descent. CONCLUSIONS: Due to the proliferation of laboratories offering genetic tests for breast cancer susceptibility, their appropriate use in public health needs careful scrutiny. Several issues are raised when such genetic tests are considered for population-based prevention programs for breast cancer. Public health agencies, such as the Centers for Disease Control and Prevention, are important to monitoring and evaluating genetic testing done outside of research protocols. If genetic tests for breast cancer are to be incorporated into future prevention programs, evaluation is needed of whether the testing can have the intended effect.

PMID: 10344217
No evidence for a role of BRCA1 or BRCA2 mutations in Ashkenazi Jewish families with hereditary prostate cancer.
... hereditary breast cancer ( BRCA1 and ... in BRCA1 and ... founder BRCA1 and ... in BRCA1 , ... the BRCA1 gene ... founder BRCA1 and ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10344217

No evidence for a role of BRCA1 or BRCA2 mutations in Ashkenazi Jewish families with hereditary prostate cancer.
Source

The Prostate (6/1/1999)

Abstract

[BACKGROUND] Two genes responsible for hereditary breast cancer ( BRCA1 and BRCA2) have been identified, and predisposing mutations identified. Several studies have provided evidence that germline mutations in BRCA1 and BRCA2 confer an increased risk of prostate cancer. Based on these findings, one might expect to find an increased frequency of mutations in these genes in family clusters of prostate cancer. The Ashkenazi Jewish population is unique in that it has an approximate 2% incidence of specific founder BRCA1 and BRCA2 mutations (i.e., 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2). [METHODS] To address the question of whether or not mutations in either of these genes were overrepresented in prostate cancer families, we searched for these mutations in germline DNA samples collected from affected and unaffected members of 18 Ashkenazi Jewish families, each having at least 3 first-degree relatives affected with prostate cancer. [RESULTS] No mutations were found in the BRCA1 gene in any of the 47 individuals tested. One individual possessed a BRCA2 mutation (6174delT). This individual was unaffected at the time of analysis, but had an affected paternal uncle, and an affected first cousin, neither of whom harbored the mutant gene. [CONCLUSIONS] In this sample of Ashkenazi prostate cancer families, the frequency of founder BRCA1 and BRCA2 mutations was not elevated, suggesting that such mutations will account for only a small, perhaps minimal, fraction of familial prostate cancer.

PMID: 10353781
Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer.
... in BRCA1 (185delAG, ... those breast cancer cases ... germline BRCA1 /BRCA2 ... or breast cancer diagnosed ... of breast cancer cases, ... and breast cancer carried ... in BRCA1 than ... with breast cancer who ... carrying BRCA1 and ... (1) breast cancer <50 ... (2) breast cancer <60 ... with breast cancer <60 ... (3) breast cancer <70 ...   (details)

BRCA1 and Breast Neoplasms

Was this association found to be significant?
Significant
Not Significant
Error

Comments

PMID: 10353781

Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer.
Source

Journal of medical genetics (May 1999)

Abstract

We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 breast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188del11) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was used to develop a model to predict those breast cancer cases likely to be germline BRCA1/BRCA2 mutation carriers in this population. The most important factors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.7%), and both cases with ovarian and breast cancer carried one of the founder mutations. Age at diagnosis in carriers (44.6 years) was significantly lower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Conversely, 12% of non-mutation carriers had strong family histories, with both a first and a second degree relative diagnosed with breast or ovarian cancer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would identify those at approximately 10% risk: (1) breast cancer <50 years, (2) breast cancer <60 years with a first degree relative with breast cancer <60 years, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.