Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

Caragh P Stapleton, Kelly A Birdwell, Amy Jayne McKnight, Alexander P Maxwell, Patrick B Mark, M Lee Sanders, Fiona A Chapman, Jessica van Setten, Paul J Phelan, Claire Kennedy, Alan Jardine, Jamie P Traynor, Brendan Keating, Peter J Conlon, Gianpiero L Cavalleri

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Abstract

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 −5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P =.0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 −5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 −7; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

Original languageEnglish
Pages (from-to)801-810
JournalAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Volume19
Issue number3
Early online date07 Aug 2018
DOIs
Publication statusPublished - 01 Mar 2019

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    Stapleton, C. P., Birdwell, K. A., McKnight, A. J., Maxwell, A. P., Mark, P. B., Sanders, M. L., Chapman, F. A., van Setten, J., Phelan, P. J., Kennedy, C., Jardine, A., Traynor, J. P., Keating, B., Conlon, P. J., & Cavalleri, G. L. (2019). Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 19(3), 801-810. https://doi.org/10.1111/ajt.15057