<i>BRCA1</i> and <i>BRCA2</i> mutations in women of different ethnicities undergoing testing for hereditary breast‐ovarian cancer

<jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (<jats:italic>BRCA1</jats:italic>) and <jats:italic>BRCA2</jats:italic> has important implications for screening and prevention counseling. Uncertainty regarding the role of <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> testing in high‐risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease‐associated) mutations in non‐white populations. In this study, the authors examined the prevalence of <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> mutations in an ethnically diverse group of women who were referred for genetic testing.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>In this cross‐sectional analysis, the prevalence of <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> mutations was assessed in a group of non‐Ashkenazi Jewish women who underwent genetic testing.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p>From 1996 to 2006, 46,276 women who met study criteria underwent DNA full‐sequence analysis of the <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non‐European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; <jats:italic>P</jats:italic> < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1‐1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1‐1.4]) ancestries had a significantly higher prevalence of deleterious <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of <jats:italic>BRCA1</jats:italic> mutations in those 2 groups. Non‐European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%→5.9%), and women of African ancestry experienced the largest decline (58%).</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p>Mutation prevalence was found to be high among women who were referred for clinical <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> testing, and the risk was similar across diverse ethnicities. <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> testing is integral to cancer risk assessment in all high‐risk women. Cancer 2009. © 2009 American Cancer Society.</jats:p></jats:sec>