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

Stapleton, C. P. et al. (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, 19(3), pp. 801-810. (doi: 10.1111/ajt.15057) (PMID:30085400)

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 general, non-transplant setting, can predict risk of, and time to post-transplant skin cancer. Genetic variants, reaching pre-defined p-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) non-transplant GWAS. Using these genome-wide association studies, 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 post-transplant. BCC PRS calculated at p-value threshold 1x10 was the most significant predictor of case:control status of NMSC post-transplant (OR=1.65; adjusted P=0.0008; AUC(full model adjusted for clinical predictors and PRS)=0.81). SCC PRS at p-value threshold 1x10 was the most significant predictor of time to post-transplant NMSC (adjusted P=8.15x10 ; HR=1.42, concordance (full model)=0.74). PRS of non-transplant NMSC is predictive of case:control status and time to NMSC post-transplant. These results are relevant to how genomics can risk stratify patients to help develop personalised treatment regimens. This article is protected by copyright. All rights reserved.

• Item Type: Articles
• Additional Information: C.P.S is supported by the Irish Research Council and Punchestown Kidney Research Fund (grant number EPSPG2015). P.J.P. is supported by an NRS Career Research Fellowship. Further thanks to funding support from Northern Ireland Kidney Research Fund and SFI-DfE (15/IA/3152).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mark, Professor Patrick and Jardine, Professor Alan
• Authors: 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., and Cavalleri, G. L.
• Subjects: R Medicine > RC Internal medicine
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Transplantation
• Publisher: Wiley
• ISSN: 1600-6135
• ISSN (Online): 1600-6143
• Published Online: 07 August 2018
• Copyright Holders: Copyright © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons
• First Published: First published in American Journal of Transplantation 19(3): 801-810
• Publisher Policy: Reproduced in accordance with the publisher copyright policy