| Literature DB >> 33579919 |
Rebecca E Graff1,2,3, Taylor B Cavazos4, Khanh K Thai2, Linda Kachuri1, Sara R Rashkin1, Joshua D Hoffman1, Stacey E Alexeeff2, Maruta Blatchins2, Travis J Meyers1, Lancelote Leong1, Caroline G Tai1, Nima C Emami1,4, Douglas A Corley2, Lawrence H Kushi2, Elad Ziv3,5,6, Stephen K Van Den Eeden2,7, Eric Jorgenson2, Thomas J Hoffmann1,2,5, Laurel A Habel2, John S Witte8,9,10,11, Lori C Sakoda12,13.
Abstract
Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.Entities:
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Year: 2021 PMID： 33579919 PMCID： PMC7880989 DOI： 10.1038/s41467-021-21288-z
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919