Breast Cancer Genetic Tests Validated for African-Americans

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Genetic testing for breast cancer susceptibility genes appears to be as potentially beneficial for high-risk African-American women as it is for high-risk white women.

The rate of deleterious mutations in the BRCA1 and BRCA2 genes of African-American women was 28%, a rate consistent with that of the general population found in other studies, reported the study’s Rita Nanda, M.D., of the University of Chicago Medical Center here.

Genetic susceptibility to breast cancer in African-American women has not been well studied, despite a high incidence of early-onset Breast cancer in this population, Dr. Nanda and colleagues noted in the Oct. 19 issue of the Journal of the American Medical Association.

The study included 155 families at high-risk for Breast cancer. This was defined as families having two or more cases of Breast cancer, ovarian cancer, or both, among first- and second-degree relatives. This group was 50% non-Ashkenazi Jewish white, 19% Ashkenazi Jewish, 28% African American, and a small percentage of other ethnicities.

In each family, the individual with the highest probability of carrying BRCA1 or BRCA2 mutations was genetically tested. The main outcome measures were frequency of mutations and area under the receiver operating curve for the BRCAPRO model, which predicts the likelihood of carrying BRCA1 or BRCA2 mutations.

The rate of mutations in African American women was 27.9% compared with 46.2% for non-Ashkenazi Jewish white women and 69% for Ashkenazi Jewish women. The lower rate in African-Americans was not statistically significant when co-variates measuring family history were adjusted. This rate is also comparable to that found in the general population by other studies: one study reported a rate of 22%, while another reported 17%, the researchers noted.

In addition, African-American women had a higher rate of polymorphism and variants of unknown significance in BRCA1 and BRCA2 than whites (44.2% versus 11.5%; P<.001). The role that these variants play in the etiology of Breast cancer is still not understood, the researchers said.

The BRCAPRO model performed as well in African-American families as it did in white or Jewish families, with an area under the curve of 0.77 (95% confidence interval=0.61-0.88) for African-American families and 0.70 (95% CI=0.60-0.79) for white and Jewish families combined.

“These data support the use of BRCAPRO and genetic testing for BRCA1 and BRCA2 mutations in the management of high-risk African American families,” the study authors concluded. “Irrespective of ancestry, early age at diagnosis and a family history of breast and ovarian cancer are the most powerful predictors of mutation status and should be used to guide clinical decision making.”

The researchers added, “Our observations underscore the need for large, collaborative studies to systematically validate the role of genetic testing, the use of risk prediction models, and the role of risk-reducing strategies in improving health outcomes for individuals of African ancestry,”

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