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    Polygenic risk scores stratify keratinocyte cancer risk among solid organ transplant recipients with chronic immunosuppression in a high ultraviolet radiation environment.

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    Authors
    Seviiri, M.
    Law, M. H.
    Ong, J. S.
    Gharahkhani, P.
    Nyholt, D. R.
    Hopkins, P.
    Chambers, D.
    Campbell, S.
    Isbel, N. M.
    Soyer, H. P.
    Olsen, C. M.
    Ellis, J. J.
    Whiteman, D. C.
    Green, Adèle C
    MacGregor, S.
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    Affiliation
    Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia
    Issue Date
    2021
    
    Metadata
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    Abstract
    Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high UVR environments. We assessed whether polygenic risk scores can improve the prediction of BCC and SCC risks and multiplicity over and above the traditional risk factors in SOTRs in a high UV setting. We built polygenic risk scores for BCC (n = 594,881) and SCC (n = 581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Sun and Health Study cohort (n > 6,300), and applied them in SOTRs in the skin tumor in allograft recipients cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk = 45.45%, 95% confidence interval = 33.14-58.19%) and SCC (absolute risk = 44.12%, 95% confidence interval = 32.08-56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to those in the bottom quintile. The respective polygenic risk scores improved risk predictions by 2% for BCC (area under the curve = 0.77 vs. 0.75, P = 0.0691) and SCC (area under the curve = 0.84 vs. 0.82, P = 0.0260), over and above the established risk factors, and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The polygenic risk scores also added predictive accuracy for tumor multiplicity (BCC R2 = 0.21 vs. 0.19, P = 3.2 × 10-3; SCC R2 = 0.30 vs. 0.27, P = 4.6 × 10-4).
    Citation
    Seviiri M, Law MH, Ong JS, Gharahkhani P, Nyholt DR, Hopkins P, et al. Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet Radiation Environment. Journal of Investigative Dermatology . 2021 Jun.
    Journal
    Journal of Investigative Dermatology
    URI
    http://hdl.handle.net/10541/624390
    DOI
    10.1016/j.jid.2021.03.034
    PubMed ID
    34089721
    Additional Links
    https://dx.doi.org/10.1016/j.jid.2021.03.034
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jid.2021.03.034
    Scopus Count
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    All Paterson Institute for Cancer Research

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