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A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma

Author

Listed:
  • Mathias Seviiri

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology
    Queensland University of Technology)

  • Matthew H. Law

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology)

  • Jue-Sheng Ong

    (QIMR Berghofer Medical Research Institute)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute)

  • Pierre Fontanillas

    (23andMe, Inc)

  • Catherine M. Olsen

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • David C. Whiteman

    (University of Queensland)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology)

Abstract

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.

Suggested Citation

  • Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35345-8
    DOI: 10.1038/s41467-022-35345-8
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