Abstract
BackgroundGenetic testing for germline cancer susceptibility genes is widely available. The Ask2Me.org (All Syndromes Known to Man Evaluator) tool is a clinical decision support tool that provides evidence-based risk predictions for individuals with pathogenic variants in cancer susceptibility genes.ObjectiveThe aim of this study was to understand the search behavior of the Ask2Me.org tool users, identify the patterns of queries entered, and discuss how to further improve the tool.MethodsWe analyzed the Ask2Me.org user-generated queries collected between December 12, 2018, and October 8, 2019. The gene frequencies of the user-generated queries were compared with previously published panel testing data to assess the correspondence between usage and prevalence of pathogenic variants. The frequencies of prior cancer in the user-generated queries were compared with the most recent US population–based cancer incidence.ResultsA total of 10,085 search queries were evaluated. The average age submitted in the queries was 48.8 (SD 16.5) years, and 84.1% (8478/10,085) of the submitted queries were for females. BRCA2 (1671/10,085, 16.6%), BRCA1 (1627/10,085, 16.1%), CHEK2 (994/10,085, 9.9%), ATM (662/10,085, 6.6%), and APC (492/10,085, 4.9%) were the top 5 genes searched by users. There was a strong linear correlation between genes queried by users and the frequency of pathogenic variants reported in published panel testing data (r=0.95, r2=0.90, P<.001). Over half of the queries (5343/10,085, 53.0%) included a prior personal history of cancer. The frequencies of prior cancers in the queries on females were strongly correlated with US cancer incidences (r=0.97, r2=0.95, P<.001), while the same correlation was weaker among the queries on males (r=0.69, r2=0.47, P=.02).ConclusionsThe patients entered in the Ask2Me.org tool are a representative cohort of patients with pathogenic variants in cancer susceptibility genes in the United States. While a majority of the queries were on breast cancer susceptibility genes, users also queried susceptibility genes with lower prevalence, which may represent a transformation from single gene testing to multigene panel testing. Owing to these changing tides, more efforts are needed to improve evidence-based clinical decision support tools to better aid clinicians and their practice.
Highlights
Since the commercialization of BRCA1 and BRCA2 testing in 1996, the costs of DNA sequencing and genetic testing have dropped rapidly [1]
The patients entered in the All Syndromes Known to Man Evaluator (Ask2Me).org tool are a representative cohort of patients with pathogenic variants in cancer susceptibility genes in the United States
While a majority of the queries were on breast cancer susceptibility genes, users queried susceptibility genes with lower prevalence, which may represent a transformation from single gene testing to multigene panel testing
Summary
Since the commercialization of BRCA1 and BRCA2 testing in 1996, the costs of DNA sequencing and genetic testing have dropped rapidly [1]. One major challenge for clinicians in dealing with positive genetic testing results is to provide patients with accurate cancer risk estimates. Literature regarding the magnitude of cancer risk for specific pathogenic variants (ie, penetrance) often varies in quality and study design. It is almost impossible for busy providers to keep up with the rapidly growing literature, carefully evaluate each study, and select the most reliable risk estimate [5,6]. Genetic testing for germline cancer susceptibility genes is widely available. The Ask2Me.org (All Syndromes Known to Man Evaluator) tool is a clinical decision support tool that provides evidence-based risk predictions for individuals with pathogenic variants in cancer susceptibility genes
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