Racial Differences in the incidence of BRCA1 and BRCA2 mutations in a cohort of Early Onset Breast Cancer patients: African American compared to White Women

Bruce Haffty ^1*, Andrea Silber ², Ellen Matloff ³, Joyce Chung ⁴ and Donald Lannin ³

¹ RWJMS-UMDNJ, United States
² Yale, United States
³ Yale University
⁴ Hospital of St. Raphael

^* To whom correspondence should be addressed. E-mail: hafftybg{at}umdnj.edu.

Accepted 18 June 2005

Abstract

Purpose: To evaluate the frequency and distribution of BRCA1 and BRCA2, in a cohort of young women with breast cancer, and to compare the distribution of mutations as a function of race.

Methods and materials: 200 women with known breast cancer diagnosed at a young age (45 years or less), and treated with radiation therapy were invited to participate in this study. After IRB approved informed consent, patients underwent complete sequencing of the BRCA1 and BRCA2 genes. In the current analysis, 170 white women were compared to 30 African American women. The white cohort as well as the African American cohort represented approximately 40% of women aged 45 years or younger in the data base.

Results: Of the 200 patients tested, 131 (65 %) were wild type, 34 (17%) had deleterious mutations and 35 (18%) had variants of uncertain significance. There were no significant differences between the White and African American cohorts with respect to the percentage of deleterious mutations (17% v. 17%). However, the majority of African American patients had mutations in BRCA2 (4/5-80%), while the majority of mutations in the white cohort were in BRCA1 (20/29-69%). In addition, a larger number of African American women had variants of uncertain significance (46%), compared to only 12% variants of uncertain significance in the white cohort. Review of the variants of uncertain significance in both cohorts revealed the majority to be unlikely associated with disease risk or likely to be polymorphisms.

Conclusions: Young African American women with breast cancer have a similar frequency of deleterious mutations as white women. However, African American women have a significantly higher frequency of variants of uncertain significance. Review of these variants revealed the majority to be unlikely associated with disease risk. Implications for genetic testing and counseling in young women with breast cancer are discussed.

Keywords: BRCA1/BRCA2, breast cancer, mutations, race

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