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New study provides a clearer picture of breast-cancer gene mutations in American women

17.08.2006
Findings shed new light on mutation risk in older and African-American women

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 BRCA 1 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.

Kristen Woodward | EurekAlert!
Further information:
http://www.fhcrc.org

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