BRCA1/2 mutations and cancer risk in Asian-Americans

• Published in: Journal of clinical oncology Vol. 25; no. 18_suppl; p. 10512
• Main Authors: Kurian, A. W., Chun, N. M., Mills, M. A., Staton, A. D., Crawford, B. A., Ridge, Y., Donlon, S. S., Gong, G. D., West, D. W., Ford, J. M.
• Format: Journal Article
• Language: English
• Published: 20.06.2007
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2007.25.18_suppl.10512

Abstract only 10512 Background: There are significant differences in breast cancer epidemiology between Caucasian and Asian-Americans and even between different Asian groups. These cancer risks and associated BRCA1/2 mutation prevalence have not been well defined in Asians; BRCA1/2 mutation penetrance might differ due to different risk modifiers. We report on a case-control study of BRCA1/2 mutation prevalence and cancer risk in Asian-American women. Methods: Clinical Data Collection: Chart review from cancer genetics services of 4 North American centers with highest Asian volume. BRCA1/2 Mutation Risk Assessment: BRCAPRO and Myriad II models, CancerGene version 4.3 (University of Texas). BRCA1/2 Mutation Testing: Full sequencing and large rearrangement panel (Myriad Genetics Inc.). Endpoints: BRCA1/2 mutation prevalence and predictive model accuracy (observed versus predicted mutations). Results: 43 of 181 Asians (23.8%) had a BRCA1/2 mutation; 36 (19.9%) had a variant of uncertain significance. The observed prevalence of BRCA1/2 mutations was 23.8% of women, which differs significantly from the predicted prevalence of 12.9% using BRCAPRO (p = 5.6 × 10 -9 ), and the predicted prevalence of 12.6% using Myriad II. This 2-fold difference existed for Chinese, Japanese, and Filipina women (the ethnic sub-groups with enough cases available for comparisons), even though the percent with observed and predicted mutations varied for these three groups. Conclusions: One in 4 clinically tested Asian-Americans has a BRCA1/2 mutation. Standard models significantly under-predict mutations in Asians; consequently, Asians are likely under-tested for BRCA1/2 mutations. These results may reflect lower BRCA1/2-associated cancer risk in Asians compared to Caucasians. Comparison to Caucasian controls and to Asians in Hong Kong is underway, to investigate potential genetic and lifestyle modifiers of BRCA1/2-associated cancer risk. [Table: see text] No significant financial relationships to disclose.