Kurian Allison W, Gong Gail D, Chun Nicolette M, Mills Meredith A, Staton Ashley D, Kingham Kerry E, Crawford Beth B, Lee Robin, Chan Salina, Donlon Susan S, Ridge Yolanda, Panabaker Karen, West Dee W, Whittemore Alice S, Ford James M
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5405, USA.
J Clin Oncol. 2008 Oct 10;26(29):4752-8. doi: 10.1200/JCO.2008.16.8310. Epub 2008 Sep 8.
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.
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.
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.
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.
亚洲人和白人在乳腺癌流行病学方面存在既定差异，但对于亚洲人群中的遗传性乳腺癌了解甚少。尽管越来越多的亚洲人接受了BRCA1/2突变的临床检测，但尚不清楚预测突变的计算机模型在亚洲人中是否能准确发挥作用。我们比较了两种广泛使用的BRCA1/2突变预测模型BRCAPRO和Myriad II在亚洲人和白人中的表现。
我们在四家癌症遗传学诊所对200名亚洲个体和200名白人个体组成的匹配对照组进行了BRCA1/2突变检测，通过比较观察到的与预测的突变携带者数量，并评估每个模型的受试者操作特征曲线下面积（AUC），对BRCAPRO和Myriad II进行了评估。
BRCAPRO和Myriad II准确预测了白人BRCA1/2突变携带者的数量（观察到25例，BRCAPRO预测24例；Myriad II预测25例，P≥0.69），但对亚洲携带者的预测少了两倍（观察到49例，BRCAPRO预测25例；Myriad II预测26例；P≤3×10⁻⁷）。对于BRCAPRO，这种种族差异反映出对亚洲BRCA2突变携带者的预测严重不足（观察到26例，预测4例；P = 1×10⁻³⁰）；对于Myriad II，无法获得单独的突变预测。对于这两种模型，亚洲人的AUC均略低于白人，但差异不显著，表明在区分亚洲携带者和非携带者方面准确性较低。
与白人相比，BRCAPRO和Myriad II在亚洲人中均低估了BRCA1/2突变携带者的比例，且在区分携带者和非携带者方面表现较差。
