A clinic-based study of BRCA1/2 mutation epidemiology in Asians

Abstract

Background: Previous research suggests significant differences in the epidemiology of breast cancers associated with BRCA1/2 mutations among Asians and Caucasians. The BRCAPRO and Myriad II models are widely used to predict BRCA1/2 mutation carriage, but their accuracy has not been studied in Asians. We are conducting a clinic-based study of BRCA1/2 mutation prevalence, epidemiology of associated cancers, and performance of the BRCAPRO and Myriad II models in Asians and Caucasians. Methods: Patient clinical data and BRCA1/2 mutation testing results were collected through chart and database review from cancer genetics services at North American medical centers with a high volume of Asian patients. BRCA1/2 mutation testing was performed through full sequencing and evaluation for common gene rearrangements, in most cases by Myriad Genetics Incorporated (Salt Lake City, UT). BRCAPRO and Myriad II model scores were calculated centrally using CancerGene software, version 4b (University of Texas Southwestern, Dallas, TX). Results: Data are presented from the British Columbia Cancer Agency, Stanford University, and University of California at San Francisco. 41 of 126 patients (32.5%) carried a deleterious mutation in BRCA1 or BRCA2; 24 (19.0%) had a variant of uncertain signifi cance in one of these genes. The mean predicted probability of BRCA1/2 mutation carriage using the BRCAPRO model was 13.5%, which is signifi cantly (p<0.00001) different from the observed 32.5% of women with BRCA1/2 mutations, and 14.1% using the Myriad II model. Conclusions: Approximately one-third of clinically tested Asian women carry a deleterious mutation in BRCA1 or BRCA2. The BRCAPRO and Myriad II models under-estimated probability of mutation carriage in Asians. Comparison to Caucasian controls and to Asian patients in Hong Kong is underway to evaluate differences in BRCA1/2 mutation prevalence, epidemiology of associated cancers, and model performance.