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Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts

Author

Listed:
  • Rebecca E. Graff

    (University of California San Francisco
    Kaiser Permanente Northern California
    University of California San Francisco)

  • Taylor B. Cavazos

    (Program in Biological and Medical Informatics, University of California San Francisco)

  • Khanh K. Thai

    (Kaiser Permanente Northern California)

  • Linda Kachuri

    (University of California San Francisco)

  • Sara R. Rashkin

    (University of California San Francisco)

  • Joshua D. Hoffman

    (University of California San Francisco)

  • Stacey E. Alexeeff

    (Kaiser Permanente Northern California)

  • Maruta Blatchins

    (Kaiser Permanente Northern California)

  • Travis J. Meyers

    (University of California San Francisco)

  • Lancelote Leong

    (University of California San Francisco)

  • Caroline G. Tai

    (University of California San Francisco)

  • Nima C. Emami

    (University of California San Francisco
    Program in Biological and Medical Informatics, University of California San Francisco)

  • Douglas A. Corley

    (Kaiser Permanente Northern California)

  • Lawrence H. Kushi

    (Kaiser Permanente Northern California)

  • Elad Ziv

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Stephen K. Eeden

    (Kaiser Permanente Northern California
    University of California San Francisco)

  • Eric Jorgenson

    (Kaiser Permanente Northern California)

  • Thomas J. Hoffmann

    (University of California San Francisco
    Kaiser Permanente Northern California
    University of California San Francisco)

  • Laurel A. Habel

    (Kaiser Permanente Northern California)

  • John S. Witte

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Lori C. Sakoda

    (Kaiser Permanente Northern California
    Kaiser Permanente Bernard J. Tyson School of Medicine)

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.

Suggested Citation

  • Rebecca E. Graff & Taylor B. Cavazos & Khanh K. Thai & Linda Kachuri & Sara R. Rashkin & Joshua D. Hoffman & Stacey E. Alexeeff & Maruta Blatchins & Travis J. Meyers & Lancelote Leong & Caroline G. Ta, 2021. "Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21288-z
    DOI: 10.1038/s41467-021-21288-z
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