Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk
Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk
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DOI：
10.1038/gim.2017.96
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发表时间：
2018-02-01
影响因子：
8.8
通讯作者：
Kurian, Allison W.
中科院分区：
文献类型：
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作者：
Caswell-Jin, Jennifer L.;Gupta, Tanya;Kurian, Allison W.
目的：我们检查了种系多基因测序（MGS）小组使用和结果的种族/民族差异，以评估遗传性癌症风险。方法：我们收集了2013年1月1日至2015年12月31日期间在斯坦福大学接受MGS的1，483名患者的基因检测结果和临床信息。结果：亚裔和西班牙裔的MGS年龄低于白人（48和47 vs. 55; P = 5E-16和5E-14）。在所有小组中，致病性变异的发生率（15%）在种族组之间没有显著差异。不同基因的比率确实不同：特别是，白人携带致病性CHEK 2变异体的百分比高于非白人（3.8%对1.0%; P = 0.002）。非白种人的不确定显著性变异（VUS）结果的发生率高于白种人（36% vs. 27%; P = 2 E-4）。VUS的可能性随着检测基因数量的增加而增加;这种影响对非白人比白人更明显（检测BRCA 1/2的VUS率绝对差异为1.1%，检测13个基因的VUS率绝对差异为8%，检测28个基因的VUS率绝对差异为14%），加剧了差异。结论：在这个接受MGS检测的多元化队列中，不同种族/民族之间的致病性变异率相似。相比之下，VUS结果在非白人中更常见，对MGS测试的种族/民族影响具有潜在意义。
Purpose: We examined racial/ethnic differences in the usage and results of germ-line multiple-gene sequencing (MGS) panels to evaluate hereditary cancer risk.Methods: We 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.Results: Asians 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.Conclusion: In 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.