1. Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort.
- Author
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Stapleton CP, Birdwell KA, McKnight AJ, Maxwell AP, Mark PB, Sanders ML, Chapman FA, van Setten J, Phelan PJ, Kennedy C, Jardine A, Traynor JP, Keating B, Conlon PJ, and Cavalleri GL
- Subjects
- Carcinoma, Basal Cell diagnosis, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell etiology, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell etiology, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Genome-Wide Association Study, Humans, Incidence, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications etiology, Prognosis, Risk Factors, Skin Neoplasms epidemiology, Skin Neoplasms etiology, Transplant Recipients, United States epidemiology, Biomarkers, Tumor genetics, Kidney Failure, Chronic surgery, Kidney Transplantation adverse effects, Polymorphism, Single Nucleotide, Postoperative Complications diagnosis, Skin Neoplasms diagnosis
- 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., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)- Published
- 2019
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