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NCI CANCERLIT® Search: BRCA1 Gene - October 2001
National Cancer Institute®
Last Modified: November 21, 2001
Table of Contents
1
UI - 21381862
AU - Markman M
TI -
Is it good clinical judgment or selection bias?
SO - Curr Oncol Rep 2001 Sep;3(5):377-8
2
UI - 21454126
AU - Piek JM; van Diest PJ; Zweemer RP; Kenemans P; Verheijen RH
TI -
Tubal ligation and risk of ovarian cancer.
SO - Lancet 2001 Sep 8;358(9284):844
3
UI - 21468599
AU - Esteller M
TI -
Epigenetic lesions causing genetic lesions in human cancer: promoter
hypermethylation of DNA repair genes.
SO - Eur J Cancer 2000 Dec;36(18):2294-300
AD - Division of Cancer Biology, The Johns Hopkins Oncology Center,
Baltimore, MD 21231, USA. esteller@welchlink.welch.jhu.edu
The existence of genetic alterations affecting genes involved in
cellular proliferation and death, such as TP53 and K-ras, is one of the
most common features of tumour cells. Recently, gene inactivation by
promoter hypermethylation has been demonstrated. Methylation is the main
epigenetic modification in mammals and abnormal methylation of the CpG
islands located in the promoter region of the genes leads to
transcriptional silencing. Examples include the p16INK4a, p15INK4B,
p14ARF, Von Hippel-Lindau (VHL), the oestrogen and progesterone
receptors, E-cadherin, death associated protein (DAP) kinase and the
first tumour suppressor gene described, retinoblastoma (Rb) gene. In
most cases, methylation involves loss of expression, absence of a coding
mutation and restoration of transcription by the use of demethylating
agents. However, is there a linkage between genetic and epigenetic
alterations? Our results show one side of this puzzle demonstrating that
epigenetic lesions drive genetic lesions in cancer. Four specific
epigenetic lesions, promoter hypermethylation of the DNA mismatch repair
gene hMLH1, the DNA alkyl-repair gene O(6)-methylguanine-DNA
methyltransferase (MGMT), the detoxifier glutathione S-transferase P1
(GSTP1) and the familial breast cancer gene BRCA1 may lead to four
specific genetic lesions, microsatellite instability, G to A
transitions, steroid-related adducts and double-strand breaks in DNA.
This is probably only the beginning of an extensive list of epigenetic
events that change and make the genetic environment of the transformed
cell unstable.
4
UI - 21427140
AU - Stefanek M; Hartmann L; Nelson W
TI -
Risk-reduction mastectomy: clinical issues and research needs.
SO - J Natl Cancer Inst 2001 Sep 5;93(17):1297-306
AD - Behavioral Research Program, Division of Cancer Control and Population
Sciences, National Cancer Institute, Bethesda, MD, USA. ms496r@nih.gov
Risk-reduction mastectomy (RRM), also known as bilateral prophylactic
mastectomy, is a controversial clinical option for women who are at
increased risk of breast cancer. High-risk women, including women with a
strong family history of breast cancer and BRCA1/2 mutation carriers,
have several clinical options: risk-reduction surgery (bilateral
mastectomy and bilateral oophorectomy), surveillance (mammography,
clinical breast examination, and breast self-examination), and
chemoprevention (tamoxifen). We review research in a number of areas
central to our understanding of RRM, including recent data on 1) the
effectiveness of RRM in reducing breast cancer risk, 2) the perception
of RRM among women at increased risk and health-care providers, 3) the
decision-making process for follow-up care of women at high risk, and 4)
satisfaction and psychological status after surgery. We suggest areas of
future research to better guide high-risk women and their health-care
providers in the decision-making process.
5
UI - 21453507
AU - Evans D; Lalloo F; Shenton A; Boggis C; Howell A
TI -
Uptake of screening and prevention in women at very high risk of breast
cancer.
SO - Lancet 2001 Sep 15;358(9285):889-90
Management of women at high lifetime risk of familial breast cancer is
hampered because of limited data concerning the appropriateness of
treatment options. Over the past 8 years women at very high (>40%)
lifetime risk of breast cancer have had the option of entering two
chemoprevention treatment trials, a magnetic resonance imaging (MRI)
breast screening study, or a risk-reducing mastectomy (RRM) study. Only
10% of eligible women have entered one of the chemotherapy trials with a
similar proportion opting for RRM (>50% in mutation carriers) compared
with 60% opting for MRI screening. Future chemotherapy trials will have
to be designed to address this poor recruitment.
6
UI - 21445115
AU - Vogel VG
TI -
Reducing the risk of breast cancer with tamoxifen in women at increased
risk.
SO - J Clin Oncol 2001 Sep 15;19(18 Suppl):87S-92S
AD - Magee-Women's Hospital, University of Pittsburgh Cancer Institute Breast
Program, University of Pittsburgh, Pittsburgh, PA 15213, USA.
vvogel@mail.magee.edu
Validated quantitative models are available that permit the accurate
estimation of a woman's risk of developing invasive breast cancer during
a specified period of time. Data from the National Surgical Adjuvant
Breast and Bowel Project Breast Cancer Prevention Trial indicate that
tamoxifen can reduce the risk of developing breast cancer by at least
49% in women who are at increased risk. All premenopausal women whose
5-year risk of developing breast cancer is 1.67% or greater derive a net
benefit from taking tamoxifen for risk reduction. Women who have either
lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia
derive an even greater net benefit. Women who carry mutations in either
the BRCA1 or BRCA2 gene will also experience reduced incidence of breast
cancer with tamoxifen. Although postmenopausal women derive a net
benefit from tamoxifen through the reduction of both breast cancer and
bone fracture event rates, the risks of both invasive endometrial cancer
and thromboembolic events must be balanced in older women. Physicians
should identify appropriate candidates with whom to discuss the possible
benefits of tamoxifen for reducing the risk of breast cancer.
7
UI - 21441861
AU - Butler D; Goodman S
TI -
French researchers take a stand against cancer gene patent.
SO - Nature 2001 Sep 13;413(6852):95-6
8
UI - 21243555
AU - Tsuchida S; Ikemoto S; Tagawa M
TI -
Microsatellite polymorphism in intron 14 of the canine BRCA1 gene.
SO - J Vet Med Sci 2001 Apr;63(4):479-81
AD - Division of Veterinary Surgery, Nippon Veterinary and Animal Science
University, Musashino-shi, Tokyo, Japan.
Microsatellite polymorphism due to differences in CT dinucleotide
repeats was demonstrated in intron 14 of the canine BRCA1 gene. Genotype
analysis of 103 unrelated dogs from 30 different breeds detected the
presence of five alleles, including 10 of the expected 15 genotypes.
Gene frequencies were biased and all alleles with the exception of one
were below 0.1. This polymorphism, which occurs at the intron of canine
BRCA1 should prove to be a useful marker for detecting the loss of
heterozygosity (LOH). One of the more notable findings of the present
study was the detection of homozygotes of rare alleles. This finding
identified an accumulation of rare alleles in specific canine breeds and
demonstrated the usefulness of this characteristic for the biological
study of dog evolution.
9
UI - 21385555
AU - Boetes C; Stoutjesdijk M
TI -
MR imaging in screening women at increased risk for breast cancer.
SO - Magn Reson Imaging Clin N Am 2001 May;9(2):357-72, vii
AD - Department of Radiology, University Medical Center St. Radboud,
Nijmegen, The Netherlands. c.boetes@rdiag.azn.nl
Hereditary breast cancer accounts for 5% to 10% of the total breast
cancer burden. Screening of this group of women has been done by
palpation and conventional mammography until recently, but because of
the age group, mammography has a limited value. MR mammography has been
demonstrated to be a reliable imaging modality in this group of
patients.
10
UI - 21469896
AU - Chu CS; Morgan MA; Randall TC; Bandera CA; Rubin SC
TI -
Survival of BRCA1 negative ovarian cancer patients based on family
history.
SO - Gynecol Oncol 2001 Oct;83(1):109-14
AD - Division of Gynecologic Oncology, University of Pennsylvania Health
System, Philadelphia, Pennsylvania 19104, USA. chuc@mail.obgyn.upenn.edu
OBJECTIVE: To compare survival of ovarian cancer patients with and
without a family history of breast or ovarian cancer who are known to be
without mutations in BRCA1. METHODS: Patients with ovarian cancer were
tested for germline mutations in BRCA1 by polymerase chain reaction
amplification of DNA for single-strand conformation polymorphism and
direct sequencing analysis to examine the 22 coding exons of BRCA1 in
fresh and archived tumor specimens. Demographic and survival data were
collected for statistical analysis. Survival data were calculated by the
method of Kaplan and Meier and compared by the log-rank test. RESULTS:
Of the 110 patients tested at our institution, 100 were noted to be
negative for BRCA1 mutations. After exclusion of nonepithelial
histologies, benign tumors, primary peritoneal carcinoma, and incomplete
staging, 87 patients remained for analysis, of which 37 demonstrated a
family history of breast or ovarian cancer. The two groups showed
similar age at diagnosis, stage, grade, residual disease, and type of
chemotherapy. Median actuarial survival was 75 months for those patients
with a family history versus 70 months for those without (P = 0.73).
Evaluation of patients with two or more relatives with breast or ovarian
cancer also revealed no differences in survival. CONCLUSIONS: Family
history of breast or ovarian cancer does not affect survival of patients
with ovarian cancer in the absence of mutations in BRCA1. Previously
described differences in survival among patients with BRCA1 mutations
may be more related to genetic factors than to biases introduced by the
presence of family history. Copyright 2001 Academic Press.
11
UI - 21469910
AU - Quillin JM; Boardman CH; Bodurtha J; Smith T
TI -
Preventive gynecologic surgery for BRCA1/2 carriers--information for
decision-making.
SO - Gynecol Oncol 2001 Oct;83(1):168-70
12
UI - 98298574
AU - Marshall A
TI -
Genetic tests forge ahead, despite scientific concerns.
SO - Nat Biotechnol 1996 Dec;14(13):1642-3
13
UI - 97322580
AU - Lynch HT; Lemon SJ; Durham C; Tinley ST; Connolly C; Lynch JF; Surdam J;
TI -
Orinion E; Slominski-Caster S; Watson P; Lerman C; Tonin P; Lenoir G;
Serova O; Narod S
A descriptive study of BRCA1 testing and reactions to disclosure of test
results.
SO - Cancer 1997 Jun 1;79(11):2219-28
AD - Creighton University, Department of Preventive Medicine, Omaha, Nebraska
68178, USA.
BACKGROUND: The identification of the BRCA1 gene is a powerful tool for
predicting a patient's lifetime risk for carcinoma of the breast and
ovary when she has hereditary breast/ovarian carcinoma (HBOC) syndrome.
The process of BRCA1 testing and genetic counseling and participants'
reactions to test results, are described. METHODS: Education about the
natural history of HBOC syndrome and the pros and cons of genetic
testing was provided to 14 HBOC families comprised of 2549 bloodline
relatives. Of these, 388 underwent DNA testing. After informed consent
was given by participants, formal linkage analysis and gene mutation
studies were performed on the families. Qualitative data on intentions
and emotional reactions were collected by physicians/counselors during
the genetic counseling sessions. RESULTS: Of those tested, 181 received
their results after further genetic counseling. Seventy-eight of them
were positive and 100 were negative for BRCA1 gene mutation. Three had
ambiguous findings. The most common reasons given for seeking DNA
testing were concern about risk to children and concern about
surveillance and prevention. Prophylactic mastectomy was considered by
35% of women who tested positive, whereas prophylactic oophorectomy was
considered an important option by 76%. Twenty-five percent of both BRCA1
positive and negative individuals were concerned about discrimination by
insurance companies. Eighty percent of those who tested negative
reported emotional relief, whereas over one-third of those who tested
positive reported sadness, anger, or guilt. CONCLUSIONS: DNA testing of
patients with HBOC syndrome must be performed in the context of genetic
counseling. The authors' results demonstrate the many complex clinical
and nonclinical issues that are important in this process.
14
UI - 99317170
AU - Goldworth A
TI -
Informed consent in the genetic age.
SO - Camb Q Healthc Ethics 1999 Summer;8(3):393-400
AD - Lucille Packard Children's Hospital, Stanford University, Palo Alto, CA,
USA.
15
UI - 97299454
AU - Cunningham GC
TI -
A public health perspective on the control of predictive screening for
breast cancer.
SO - Health Matrix Clevel 1997 Winter;7(1):31-48
AD - Pacific Southwest Regional Genetics Network, USA.
16
UI - 97299456
AU - Dorff EN
TI -
Jewish theological and moral reflections on genetic screening: the case
of BRCA1.
SO - Health Matrix Clevel 1997 Winter;7(1):65-96
AD - University of Judaism, Los Angeles, CA, USA.
17
UI - 21230513
AU - Campbell M; Aprelikova ON; van der Meer R; Woltjer RL; Yee CJ; Liu ET;
TI -
Jensen RA
Construction and characterization of recombinant adenoviruses expressing
human BRCA1 or murine Brca1 genes.
SO - Cancer Gene Ther 2001 Mar;8(3):231-9
AD - Department of Pathology, Vanderbilt University Medical Center,
Nashville, Tennessee 37232, USA. mel.campbell@mcmail.vanderbilt.edu
Recombinant adenoviruses expressing human BRCA1 (AdBRCA1), murine Brca1
(AdBrca1), three clinically relevant human mutant BRCA1 proteins (t340,
C61G, and 1853Stop), or a murine Brca1 C-terminal deletion mutant were
constructed and evaluated in vitro. These recombinants were capable of
transducing high-level transgene expression to a wide variety of cell
lines in vitro. Three independent methods were utilized to monitor cell
growth following transduction with these recombinants. High-level
expression of either the human or mouse wild-type BRCA1 protein was
incompatible with maximal levels of cell growth. AdBRCA1 transduction
inhibited the outgrowth of several human breast and ovarian cell lines
in colony formation assays. Flow cytometric analysis revealed an
accumulation of the transduced cells in the G0/G1 phase of the cell
cycle. This BRCA1-mediated accumulation of cells in G0/G1 was
accompanied by an increase in the cellular level of hypophosphorylated
pRB. Ad mutant BRCA1 t340, C61G, and 1853Stop viruses were impaired, to
varying degrees, in their ability to transduce a growth-arrested state
to the target cells. Using these same three criteria, overexpression of
murine Brca1 by AdBrca1 was also capable of transducing a
growth-arrested state to human cells. Deletion of the C-terminus of
Brca1 diminished this activity. This panel of adenoviruses may be useful
reagents as part of an approach to understand the function of
BRCA1/Brca1 in normal breast and ovary and help to define the tumor
suppressor defect (s) conferred by clinical BRCA1 mutations in breast
and ovarian cell tumorigenesis.
18
UI - 21236239
AU - Plon SE; Peterson LE; Friedman LC; Richards CS
TI -
Mammography behavior after receiving a negative BRCA1 mutation test
result in the Ashkenazim: a community-based study.
SO - Genet Med 2000 Nov-Dec;2(6):307-11
AD - Department of Pediatrics, Baylor College of Medicine, Houston, Texas,
USA.
PURPOSE: To define the impact of a negative BRCA1 test result on
subsequent breast cancer screening behavior in women. METHODS:
Longitudinal study of a community-based sample of Ashkenazi Jews offered
testing for the 185delAG BRCA1 mutation in 1996. Of 309 participants,
118 women were mutation negative, of average risk (based on family
history of cancer), unaffected with breast cancer, and provided complete
data at baseline, and Year 1 and Year 2 follow-up questionnaires.
RESULTS: Women age 50 and older had 91.7% compliance with mammography
for the year prior to entry (baseline), 88.3% during Year 1, 91.7%
during Year 2 (no significant change; P = 0.775). Women under age 50
demonstrated an increase in mammography (49.2% at baseline, 62.7% Year
1, and 67.1% Year 2; P = 0.035). Both groups demonstrated significant
decreases in breast cancer worry and perceived risk. Logistic regression
analysis on having a mammogram at Year 2 showed that age, physician
recommendation, worry, and perceived risk were all significant.
CONCLUSION: Receipt of negative BRCA1 test results in a cohort of
Ashkenazi Jewish women did not have a negative impact on mammography
behavior 2 years after genetic testing.
19
UI - 21234529
AU - Arver B; Borg A; Lindblom A
TI -
First BRCA1 and BRCA2 gene testing implemented in the health care system
of Stockholm.
SO - Genet Test 2001 Spring;5(1):1-8
AD - Department of Molecular Medicin, Karolinska Institutet, Stockholm,
Sweden. brita.arver@cmm.ki.se
The aim of the study was to optimize the criteria for the BRCA1 and
BRCA2 gene testing and to improve oncogenetic counseling in the
Stockholm region. Screening for inherited breast cancer genes is
laborious and a majority of tested samples turn out to be negative. The
frequencies of mutations in the BRCA1 and BRCA2 genes differ across
populations. Between 1997 and 2000, 160 families with breast and/or
ovarian cancer were counseled and screened for mutations in the two
genes. Twenty-five BRCA1 and two BRCA2 disease-causing mutations were
found. Various factors associated with the probability of finding a
BRCA1 mutation in the families were estimated. Age of onset in different
generations and other malignancies were also studied. Families from our
region in which both breast and ovarian cancer occur were likely to
carry a BRCA1 mutation (34%). In breast-only cancer families, mutations
were found only in those with very early onset. All breast- only cancer
families with a mutation had at least one case of onset before 36 years
of age and a young median age of onset (<43 years). Other malignancies
than breast and ovarian cancers did not segregate in the BRCA1 families
and surveillance for other malignancies is not needed, in general.
Decreasing age of onset with successive generations was common and must
be taken into account when surveillance options are considered.
20
UI - 21330096
AU - Ito Y; Noguchi S; Takeda T; Matsuura N
TI -
Fas ligand expression in BRCA1-associated hereditary breast carcinoma
clearly differs from that in sporadic breast carcinoma.
SO - Breast Cancer Res Treat 2001 Mar;66(2):95-100
AD - Department of Surgery, Osaka Seamen's Insurance Hospital, Japan.
BRCA1-associated hereditary breast carcinomas (HBCs) are diagnosed at a
younger age and are known to show biological aggressiveness such as a
high histological grade, frequent aneuploidy, compared to sporadic
breast carcinomas. However, results of studies on their prognosis have
been controversial. We hypothesized that some factors such as a high
incidence of cell death could offset the aggressiveness of
BRCA1-associated HBCs, and therefore investigated Fas and Fas ligand
(Fas L) expression in 19 BRCA1-associated HBCs and 56 age-adjusted
control cases. Glandepithelial and myoepithelial cells in the mammary
glands expressed Fas in high incidence, but all were negative for Fas L.
Fas was expressed in 89.5% of BRCA1-associated HBCs and 94.4% of the
controls and no significant differences could be established between the
two groups. However, in 73.7% of BRCA1-associated HBCs, Fas L was
clearly expressed in the infiltrating mononuclear cells, whereas this
was observed in only 14.3% of the control cases and statistical
significance was established between the two groups (p < 0.0001). These
results strongly suggest that carcinoma cells in BRCA1-associated HBCs
are more likely to be attacked by mononuclear cells via Fas L, and this
may explain, at least in part, the discrepancy with respect to the
prognosis. On the other hand, carcinoma cells also expressed Fas L
significantly more often (p < 0.0001) in BRCA1-associated HBCs (52.6%)
than in sporadic cases (3.6%). This can be considered a kind of
counterattack against the mononuclear cells or, alternatively, may
enhance the Fas-Fas L pathway in an autocrine/paracrine fashion. The
clinical significance of Fas L expressing carcinoma cells remains to be
elucidated.
21
UI - 21363506
AU - Budhram-Mahadeo V; Moore A; Morris PJ; Ward T; Weber B; Sassone-Corsi P;
TI -
Latchman DS
The closely related POU family transcription factors Brn-3a and Brn-3b
are expressed in distinct cell types in the testis.
SO - Int J Biochem Cell Biol 2001 Oct;33(10):1027-39
AD - Medical Molecular Biology Unit, Institute of Child Health, University
College London, 30 Guilford Street, WC1N 1EH, London, UK.
Although the Brn-3a and Brn-3b POU family transcription factors were
originally identified in neuronal cells, their expression in some non
neuronal cell types has previously been reported. Here we report that
Brn-3a and Brn-3b are also expressed in the testis with expression of
each factor being observed at distinct stages of germ cell development.
Thus, Brn-3a is expressed in spermatogonia whereas Brn-3b expression is
observed in post-meiotic spermatids. In agreement with this, Brn-3a
expression is detectable much earlier than that of Brn-3b in testes
derived from sexually immature postnatal animals. Similarly, Brn-3b
expression is absent in knock out mice lacking a functional CREM
transcription factor in which the later stages of germ cell development
do not occur, whereas Brn-3a expression is observed at similar levels in
the testes of these knock out mice. Interestingly, the cellular pattern
of Brn-3a expression during germ cell development coincides with that of
the BRCA-1 anti-oncogene. Consistent with the possibility that Brn-3a
may regulate expression of BRCA-1 in the testis, we have shown that
Brn-3a can strongly activate the BRCA-1 promoter in co-transfection
experiments whereas Brn-3b does not have this effect. Hence, as observed
in neuronal cells, Brn-3a and Brn-3b may play distinct and important
functional roles in the regulation of gene expression during germ cell
development.
22
UI - 21471532
AU - Wadman M
TI -
Europe's patent rebellion.
SO - Fortune 2001 Oct 1;144(6):44
23
UI - 21470366
AU - Wadman M
TI -
Testing time for gene patent as Europe rebels.
SO - Nature 2001 Oct 4;413(6855):443
24
UI - 21485295
AU - Zanker KS; Anand M; Majumdar A; Daftary GV
TI -
The Mumbai Conference on Molecular Targets in Cancer Cells: new
paradigms in research and treatment.
SO - J Cancer Res Clin Oncol 2001 Oct;127(10):636-41
AD - Institute of Immunology, University of Witten/Herdecke, Germany.
ksz@uni-wh.de
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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