Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative

• Published in: JNCI : Journal of the National Cancer Institute Vol. 111; no. 1; pp. 95 - 98
• Main Authors: Caswell-Jin, Jennifer L, Zimmer, Anjali D, Stedden, Will, Kingham, Kerry E, Zhou, Alicia Y, Kurian, Allison W
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2019; Oxford Publishing Limited (England)
• Subjects: Brief Communication; Cancer; Confidence intervals; Disease control; Family; Genes; Genetic Carrier Screening - methods; Genetic Predisposition to Disease; Genetic screening; Genetic testing; Germ-Line Mutation; Health risks; Humans; Internet; Low cost; Neoplasms - diagnosis; Neoplasms - genetics; Online Systems; Prognosis
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djy147

Abstract 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.