ArticleJournal for immunotherapy of cancer2025
Germline whole-exome sequencing reveals
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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26 authors.
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Abstract
backgroundThe heritability of urinary tract cancer (UTC) remains unexplained by known pathogenic germline variants, and the influence of germline variants on treatment response to immune checkpoint inhibition (ICI) has yet to be fully elucidated.
methodsIn this case-control study, we performed a germline whole-exome sequencing of 810 UTC patients from the Oncology Research Information Exchange Network. A rare-variant burden test was conducted on the 810 patients and 2354 healthy controls from the Centre d'Etudes du Polymorphisme Humain families, the University of Utah Heritage 1000 Projects, and the 1000 Genomes Project, stratified into discovery and confirmation sets. We used a gene set-based rare-variant association test (GSRVAT) with near-match confirmation, testing for the association of pathways with UTC susceptibility and accounting for multiple testing. We then studied the impact of the identified pathways on tumor biology and clinical course among the 810 cases by analyzing their tumor exomes, transcriptomes, and clinical features.
resultsGSRVAT revealed forkhead box p3 (
conclusionsGermline variants in a set of
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