BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer.
BACKGROUND
In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 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 BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing.


METHODS
In this cross-sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non-Ashkenazi Jewish women who underwent genetic testing.


RESULTS
From 1996 to 2006, 46,276 women who met study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 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; P < .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 BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 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%).


CONCLUSIONS
Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high-risk women.
Hall
Michael J
MJ
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA. michael.hall@fccc.edu
Reid
Julia E
JE
Burbidge
Lynn A
LA
Pruss
Dmitry
D
Deffenbaugh
Amie M
AM
Frye
Cynthia
C
Wenstrup
Richard J
RJ
Ward
Brian E
BE
Scholl
Thomas A
TA
Noll
Walter W
WW
D000328:Adult; D000367:Age Factors; D044466:Asian People / Q000706:statistics & numerical data; D044383:Black People / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007843:Latin America / Q000208:ethnology; D008875:Middle Aged; D008877:Middle East / Q000208:ethnology; D054525:Minority Health; D009154:Mutation; D044465:White People / Q000706:statistics & numerical data