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Polygenic risk score as a determinant of risk of non‐melanoma skin cancer in a European‐descent renal transplant cohort
Authors: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
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.
Keywords:basic research/science  complication: malignant  dermatology  genetics  genomics  kidney transplantation/nephrology  risk assessment/risk stratification  side effects
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