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

Abstract

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. Cancer 2009. © 2009 American Cancer Society.

BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

“…To date, studies of BRCA1 mutation spectrum in Chinese populations are limited and most of these studies were performed in single institutions or a small number of medical centers .The mutation rates of BRCA1 in familial breast cancer ranged from 3.9% to 6.9% ( Cao et al, 2013). This is consistent with rates in other Asian ethnic groups (Hall et al, 2009). Another study, by Suter et al (2004) found that the rates of BRCA1 mutations in sporadic breast cancers were 0.7% (4/590) in Shanghai of China.…”

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

“…Mutation BRCA1 185delAG was the most prevalent, observed in 7 (54%) of the 13 mutation carriers, and is the most common founder mutation in the Ashkenazi Jewish population. It has also been reported in other population groups living in Mexico, Chile, and the Bahamas [19,29,30]. The frequency observed in Peru (54%) is the highest yet reported in nonselected populations in Latin America.…”

Peking University - Juntendo University Joint Symposium on Cancer Research and Treatment

“…The prevalence of mutations in BRCA1/2 is different in various ethnic groups and may be affected by founder mutations 5) . Earlier studies of BRCA1/2 mutations were largely based on Caucasian.…”

“…Earlier studies of BRCA1/2 mutations were largely based on Caucasian. It has been reported that BRCA1/2 mutations account for 15-20% of familial cases in Caucasian populations 5) . Recently, a number of studies have focused on the Chinese population.…”