Performance of BRCA1/2 mutation prediction models in Asian Americans.
OBJECTIVE
There are established differences in breast cancer epidemiology between Asian and white individuals, but little is known about hereditary breast cancer in Asian populations. Although increasing numbers of Asian individuals are clinically tested for BRCA1/2 mutations, it is not known whether computer models that predict mutations work accurately in Asian individuals. We compared the performance in Asian and white individuals of two widely used BRCA1/2 mutation prediction models, BRCAPRO and Myriad II.


METHODS
We evaluated BRCAPRO and Myriad II in 200 Asian individuals and a matched control group of 200 white individuals 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 > or = .69), but underpredicted Asian carriers by two-fold (49 observed v 25 predicted by BRCAPRO; 26 predicted by Myriad II; P < or = 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 individuals, suggesting less accurate discrimination between Asian carriers and noncarriers.


CONCLUSIONS
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 individuals.
Kurian
Allison W
AW
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5405, USA. akurian@stanford.edu
Gong
Gail D
GD
Chun
Nicolette M
NM
Mills
Meredith A
MA
Staton
Ashley D
AD
Kingham
Kerry E
KE
Crawford
Beth B
BB
Lee
Robin
R
Chan
Salina
S
Donlon
Susan S
SS
Ridge
Yolanda
Y
Panabaker
Karen
K
West
Dee W
DW
Whittemore
Alice S
AS
Ford
James M
JM
D001213:Asian / Q000235:genetics; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D003198:Computer Simulation; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D011237:Predictive Value of Tests
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