GeneDx, Gaithersburg, Maryland.
BioReference Laboratories, Inc., Elmwood Park, New Jersey.
J Genet Couns. 2020 Aug;29(4):598-606. doi: 10.1002/jgc4.1257. Epub 2020 Mar 30.
Healthcare disparities in genomic medicine are well described. Despite some improvements, we continue to see fewer individuals of African American, Asian, and Hispanic ancestry undergo genetic counseling and testing compared to those of European ancestry. It is well established that variant of uncertain significance (VUS) rates are higher among non-European ancestral groups undergoing multi-gene hereditary cancer panel testing. However, pathogenic variant (PV) yields, and genomic data in general, are often reported in aggregate and derived from cohorts largely comprised of individuals of European ancestry. We performed a retrospective review of clinical and ancestral data for individuals undergoing multi-gene hereditary cancer panel testing to determine ancestry-specific PV and VUS rates. An ancestry other than European was reported in 29,042/104,851 (27.7%) of individuals. Compared to Europeans (9.4%), individuals of Middle Eastern ancestry were more likely to test positive for one or more pathogenic variants (12.1%, p = .0025), while African Americans were less likely (7.9%, p < .0001). Asian and Middle Eastern individuals were most likely (34.8% and 33.2%, respectively) to receive a report with an overall classification of VUS, while individuals of Ashkenazi Jewish and European ancestry were least likely (17.1% and 20.4%, respectively). These data suggest that in addition to higher VUS rates, there may be ancestry-specific PV yields. Providing aggregate data derived from cohorts saturated with European individuals does not adequately reflect genetic testing outcomes in minority groups, and interrogation of ancestry-specific data is a step toward a more personalized risk assessment.
尽管已经有了一些改善,但在接受基因咨询和检测方面,非裔美国人、亚裔和西班牙裔个体的数量仍然明显少于欧洲裔个体,这种在基因组医学方面的健康差异是有据可查的。已经明确的是,在接受多基因遗传性癌症panel 检测的非欧洲裔个体中,意义未明的变异(VUS)的比例更高。然而,致病性变异(PV)的检出率,以及一般的基因组数据,通常是汇总报告的,并且源自主要由欧洲裔个体组成的队列。我们对接受多基因遗传性癌症panel 检测的个体的临床和祖先数据进行了回顾性审查,以确定特定祖先的 PV 和 VUS 率。在 104851 名个体中有 29042 名(27.7%)报告的祖先是除欧洲以外的其他地区。与欧洲人(9.4%)相比,中东地区的个体更有可能检测出一个或多个致病性变异(12.1%,p=0.0025),而非洲裔美国人则不太可能(7.9%,p<0.0001)。亚洲人和中东地区的个体最有可能(分别为 34.8%和 33.2%)收到总体分类为 VUS 的报告,而阿什肯纳兹犹太人和欧洲血统的个体则最不可能(分别为 17.1%和 20.4%)。这些数据表明,除了 VUS 比例较高之外,可能还存在特定祖先的 PV 检出率。仅提供来自欧洲个体占主导的队列汇总数据,不能充分反映少数族裔的基因检测结果,而对特定祖先数据的分析是迈向更个性化风险评估的一步。