JCO Early Release, published online ahead of print Sep 8 2008
Journal of Clinical Oncology, 10.1200/JCO.2008.16.8310
Received February 18, 2008
Accepted April 30, 2008
Performance of BRCA1/2 Mutation Prediction Models in Asian Americans
Allison W. Kurian,* Gail D. Gong, Nicolette M. Chun, Meredith A. Mills, Ashley D. Staton, Kerry E. Kingham, Beth B. Crawford, Robin Lee, Salina Chan, Susan S. Donlon, Yolanda Ridge, Karen Panabaker, Dee W. West, Alice S. Whittemore, and James M. Ford
From the Departments of Medicine, Health Research and Policy, and Genetics, Stanford University School of Medicine, Stanford; Department of Medicine, University of California at San Francisco, San Francisco, CA; Department of Medical Genetics, The Queen's Medical Center, Honolulu, HI; and the Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
* To whom correspondence should be addressed. E-mail: akurian{at}stanford.edu
Purpose: There are established differences in breast cancer epidemiology between Asian and white participants, but little is known about hereditary breast cancer in Asian populations. Although increasing numbers of Asian participants are clinically tested for BRCA1/2 mutations, it is not known whether computer models that predict mutations work accurately in Asian participants. We compared the performance in Asian and white participants of two widely used BRCA1/2 mutation prediction models, BRCAPRO and Myriad II.
Patients and Methods: We evaluated BRCAPRO and Myriad II in 200 Asian participants and a matched control group of 200 white participants who were tested for BRCA1/2 mutations at four cancer genetics clinics, by comparing numbers of observed versus predicted mutation carriers and by evaluating area under the receiver operating characteristic curve (AUC) for each model.
Results: BRCAPRO and Myriad II accurately predicted the number of white BRCA1/2 mutation carriers (25 observed v 24 predicted by BRCAPRO; 25 predicted by Myriad II, P  .69), but underpredicted Asian carriers by two-fold (49 observed v 25 predicted by BRCAPRO; 26 predicted by Myriad II; P  3 x 10-7). For BRCAPRO, this racial difference reflects substantial underprediction of Asian BRCA2 mutation carriers (26 observed v 4 predicted; P = 1 x 10-30); for Myriad II, separate mutation predictions were not available. For both models, AUCs were nonsignificantly lower in Asian than white participants, suggesting less accurate discrimination between Asian carriers and noncarriers.
Conclusion: Both BRCAPRO and Myriad II underestimated the proportion of BRCA1/2 mutation carriers, and discriminated carriers from noncarriers less well, in Asian compared with white participants.
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