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    Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population-based cohort

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    Authors
    Liyanage, U. E.
    Law, M. H.
    Antonsson, A.
    Hughes, M. C. B.
    Gordon, S.
    van der Pols, J. C.
    Green, Adèle C
    Affiliation
    QIMR Berghofer Medical Research Institute, Brisbane, Australia
    Issue Date
    2022
    
    Metadata
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    Abstract
    Background: Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). Objectives: Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well-characterised Nambour population. Methods: We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome-wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into 3 risk groups (high 20%, intermediate 60%, low 20%). Results: The fully adjusted model including traditional risk factors (phenotypic and sun exposure-related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) =1.51; 95% confidence interval (CI) =1.30-1.76, P=5.75 × 10-8 ). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR=3.45; 95% CI=2.18-5.50, P=1.5×10-7 ) and higher absolute risk of KC per 100 person-years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. Conclusions: These results show that PRS can enhance the prediction of KC above traditional risk factors.
    Citation
    Liyanage UE, Law MH, Antonsson A, Hughes MCB, Gordon S, van der Pols JC, et al. Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population-based cohort. Journal of the European Academy of Dermatology and Venereology : JEADV. 2022 Jul 26. PubMed PMID: 35881107. Epub 2022/07/27. eng.
    Journal
    Journal of the European Academy of Dermatology and Venereology
    URI
    http://hdl.handle.net/10541/625449
    DOI
    10.1111/jdv.18466
    PubMed ID
    35881107
    Additional Links
    https://dx.doi.org/10.1111/jdv.18466
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1111/jdv.18466
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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