Findings Shed New Light on Mutation Risk in Older and African-American
Women
SEATTLE, Aug. 15 /PRNewswire/ -- A large, population-based, multicenter
study led by researchers at Fred Hutchinson Cancer Research Center provides
the clearest picture yet of the prevalence and predictors of mutations in
the breast-cancer susceptibility genes BRCA1 and BRCA2 among women in the
general population.
Most research on these genes in relation to breast and ovarian cancer
has focused on rare, high-risk families and younger women. Until now, the
impact of these genetic mutations among women in the population at large --
particularly among African-Americans and those age 45 and older -- has been
understudied and, as a result, poorly understood, according to lead
investigators Kathleen E. Malone, Ph.D., Elaine A. Ostrander, Ph.D., and
colleagues, whose findings appear in the Aug. 15 issue of Cancer Research.
"Prior studies focused on high-risk families and younger, Caucasian
women. Clarifying the prevalence and predictors of these mutations in a
wider spectrum of the general population, including understudied groups
like African-Americans and older women, is important and long overdue,"
said epidemiologist Malone, a member of the Hutchinson Center's Public
Health Sciences Division.
In a study of more than 2,300 African-American and Caucasian women with
and without breast cancer from five U.S. metropolitan areas, the
researchers found that among breast-cancer cases overall, 2.4 percent and
2.3 percent carried mutations in BRCA1 and BRCA2, respectively.
BRCA1 mutations were significantly more common in white (2.9 percent)
versus black (1.4 percent) cases and in Jewish (10.2 percent) versus
non-Jewish (2.0 percent) cases. BRCA2 mutations were slightly more common
in black (2.6 percent) versus white (2.1 percent) cases.
The researchers also examined predictors of carrying a mutation in
either gene. The strongest and most significant predictors of carrying a
BRCA1 mutation were diagnosis before age 45 in the case herself or in a
relative, ovarian cancer in a relative and Jewish ancestry. Predictors of
BRCA2 mutation status included early age at diagnosis in the case herself
or in her relatives.
"These data are critical for identifying women who would most benefit
from genetic testing," said geneticist Ostrander, formerly head of the
genetics program at the Hutchinson Center who is now chief of the Cancer
Genetics Branch at the National Human Genome Research Institute.
A unique aspect of the study was the inclusion of African-American
women, Malone said. "Until now there have been very little data regarding
BRCA-carrier status in African-American women. The absence of data on such
women could lead to the misconception that they are less likely to carry a
mutation in one of these genes. In fact, this study confirms that
African-American women carry mutations in broadly similar proportions to
Caucasian women," she said.
Among breast-cancer cases with a family history of ovarian cancer, 14
percent were found to carry a BRCA 1 mutation. Among those who had a family
history of both breast and ovarian cancer, 27 percent carried a BRCA1
mutation.
While the population-based study confirmed what previously has been
observed in high-risk families -- that BRCA mutations are indeed most
common in younger women with breast cancer -- the research also provided
the first direct evidence that women diagnosed with breast cancer later in
life also can be mutation carriers, although the probability decreases with
age. The prevalence of BRCA mutations fell to about 2 percent among
breast-cancer cases diagnosed at ages 60 to 64.
According to the National Cancer Institute, more than 192,000 U.S.
women are diagnosed with breast cancer every year. Among women who carry a
mutation in BRCA1 or BRCA2, an estimated 36 percent to 85 percent (360 to
850 women out of 1,000) will get breast cancer. In addition, women with
breast cancer who carry a mutation also face an increased risk for
developing a second breast cancer or ovarian cancer.
"While the primary thrust of this research was to identify predictors
of carrying the high-risk mutations and to clarify mutation prevalence in
understudied groups, the relatively small proportion of cases found to
carry a mutation serves as a continued reminder that the majority of women
with breast cancer, even those with a positive family history, do not carry
mutations in these genes," said Malone, who is also a research professor of
epidemiology at the University of Washington School of Public Health and
Community Medicine.
For the study, Malone, Ostrander and colleagues examined the frequency
and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast
cancer and 674 women without the disease. The women ranged in age from 35
to 64 and were participants in the National Institute of Child Health and
Human Development's Women's Contraceptive and Reproductive Experiences
(CARE) Study, which involved women from the Seattle, Los Angeles, Atlanta,
Detroit and Philadelphia metropolitan areas.
The research team included investigators from the University of
Southern California in Los Angeles; Wayne State University in Detroit; the
University of Pennsylvania in Philadelphia; Bay State Medical Center in
Springfield, Mass.; the National Cancer Institute (NCI); the National
Institute of Child Health and Human Development (NICHD); and the Centers
for Disease Control and Prevention.
The NICHD and NCI funded the research.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit fhcrc.org.
CONTACT
Kristen Woodward
206-667-5095
kwoodwar@fhcrc.org
SOURCE Fred Hutchinson Cancer Research Center
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Related links:
http://www.fhcrc.org
CONTACT:
Kristen Woodward of Fred Hutchinson Cancer
Research Center, +1-206-667-5095, or kwoodwar@fhcrc.org
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