Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk. Genetics in medicine : official journal of the American College of Medical Genetics Caswell-Jin, J. L., Gupta, T. n., Hall, E. n., Petrovchich, I. M., Mills, M. A., Kingham, K. E., Koff, R. n., Chun, N. M., Levonian, P. n., Lebensohn, A. P., Ford, J. M., Kurian, A. W. 2017


PurposeWe examined racial/ethnic differences in the usage and results of germ-line multiple-gene sequencing (MGS) panels to evaluate hereditary cancer risk.MethodsWe collected genetic testing results and clinical information from 1,483 patients who underwent MGS at Stanford University between 1 January 2013 and 31 December 2015.ResultsAsians and Hispanics presented for MGS at younger ages than whites (48 and 47 vs. 55; P?=?5E-16 and 5E-14). Across all panels, the rate of pathogenic variants (15%) did not differ significantly between racial groups. Rates by gene did differ: in particular, a higher percentage of whites than nonwhites carried pathogenic CHEK2 variants (3.8% vs. 1.0%; P?=?0.002). The rate of a variant of uncertain significance (VUS) result was higher in nonwhites than whites (36% vs. 27%; P?=?2E-4). The probability of a VUS increased with increasing number of genes tested; this effect was more pronounced for nonwhites than for whites (1.1% absolute difference in VUS rates testing BRCA1/2 vs. 8% testing 13 genes vs. 14% testing 28 genes), worsening the disparity.ConclusionIn this diverse cohort undergoing MGS testing, pathogenic variant rates were similar between racial/ethnic groups. By contrast, VUS results were more frequent among nonwhites, with potential significance for the impact of MGS testing by race/ethnicity.GENETICS in MEDICINE advance online publication, 27 July 2017; doi:10.1038/gim.2017.96.

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