Polygenic risk scores stratify keratinocyte cancer risk among solid organ transplant recipients with chronic immunosuppression in a high ultraviolet radiation environment.
Law, M. H.
Ong, J. S.
Nyholt, D. R.
Isbel, N. M.
Soyer, H. P.
Olsen, C. M.
Ellis, J. J.
Whiteman, D. C.
Green, Adèle C
AffiliationStatistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia
MetadataShow full item record
AbstractSolid 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).
CitationSeviiri 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.
JournalJournal of Investigative Dermatology
- Polygenic Risk Scores Allow Risk Stratification for Keratinocyte Cancer in Organ-Transplant Recipients.
- Authors: Seviiri M, Law MH, Ong JS, Gharahkhani P, Nyholt DR, Olsen CM, Whiteman DC, MacGregor S
- Issue date: 2021 Feb
- Declining incidence of keratinocyte carcinoma in organ transplant recipients.
- Authors: Menzies S, O'Leary E, Callaghan G, Galligan M, Deady S, Gadallah B, Lenane P, Lally A, Houlihan DD, Morris PG, Sexton DJ, McCormick PA, Egan JJ, O'Neill JP, Conlon PJ, Moloney FJ
- Issue date: 2019 Nov
- Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs).
- Authors: Asgari MM, Arron ST, Warton EM, Quesenberry CP Jr, Weisshaar D
- Issue date: 2015 Sep
- Prevalence of Perineural Invasion in keratinocyte cancer in the general population and among organ transplant recipients.
- Authors: Adams A, Pandeya N, De'Ambrosis B, Plasmeijer E, Panizza B, Green AC, Olsen CM, Whiteman DC
- Issue date: 2020 Aug
- Inflammatory Dietary Patterns and Risk of Keratinocyte Cancers in Kidney Transplant Recipients: Prospective Cohort Study.
- Authors: Shao E, Green AC, Miura K
- Issue date: 2020 Sep 23