Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort
Stapleton, Caragh P.; Birdwell, Kelly A.; McKnight, Amy Jayne; Maxwell, Alexander P.; Mark, Patrick B.; Sanders, M. Lee; Chapman, Fiona A.; van Setten, Jessica; Phelan, Paul J.; Kennedy, Claire; Jardine, Alan; Traynor, Jamie P.; Keating, Brendan; Conlon, Peter J.; Cavalleri, Gianpiero L.
(2019) American Journal of Transplantation, volume 19, issue 3, pp. 801 - 810
(Article)
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,
... read more
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.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: basic research/science, complication: malignant, dermatology, genetics, genomics, kidney transplantation/nephrology, risk assessment/risk stratification, side effects, Transplantation, Pharmacology (medical), Immunology and Allergy, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 1600-6135
Publisher: Blackwell Publishing Asia Pty Ltd
Note: Publisher Copyright: © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons
(Peer reviewed)