Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Department of Scientific Affairs, Color Genomics, Burlingame, CA.
J Natl Cancer Inst. 2019 Jan 1;111(1):95-98. doi: 10.1093/jnci/djy147.
In cascade testing, genetic testing for an identified familial pathogenic variant extends to disease-free relatives to allow genetically targeted disease prevention. We evaluated the results of an online initiative in which carriers of 1 of 30 cancer-associated genes, or their first-degree relatives, could offer low-cost testing to at-risk first-degree relatives. In the first year, 1101 applicants invited 2280 first-degree relatives to undergo genetic testing. Of invited relatives, 47.5% (95% confidence interval [CI] = 45.5 to 49.6%) underwent genetic testing, and 12.0% (95% CI = 9.2 to 14.8%) who tested positive continued the cascade by inviting additional relatives to test. Of tested relatives, 4.9% (95% CI = 3.8 to 6.1%) had a pathogenic variant in a different gene from the known familial one, and 16.8% (95% CI = 14.7 to 18.8%) had a variant of uncertain significance. These results suggest that an online, low-cost program is an effective approach to implementing cascade testing, and that up to 5% of the general population may carry a pathogenic variant in 1 of 30 cancer-associated genes.
在级联检测中，对已确定的家族致病性变异进行基因检测可扩展至无疾病亲属，以进行有针对性的遗传疾病预防。我们评估了一项在线计划的结果，该计划允许 30 种癌症相关基因之一的携带者或其一级亲属对有风险的一级亲属进行低成本检测。在第一年，有 1101 名申请人邀请了 2280 名一级亲属进行基因检测。在受邀亲属中，有 47.5%（95%置信区间[CI] = 45.5 至 49.6%）接受了基因检测，其中 12.0%（95% CI = 9.2 至 14.8%）检测呈阳性的亲属继续通过邀请其他亲属进行检测来级联。在接受检测的亲属中，有 4.9%（95% CI = 3.8 至 6.1%）在与已知家族基因不同的基因中携带致病性变异，有 16.8%（95% CI = 14.7 至 18.8%）携带意义不明的变异。这些结果表明，在线、低成本计划是实施级联检测的有效方法，多达 5%的普通人群可能在 30 种癌症相关基因之一中携带致病性变异。
