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

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...

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Bibliographic Details
Published in:American journal of transplantation 2019-03, Vol.19 (3), p.801-810
Main Authors: 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.
Format: Article
Language:English
Subjects:
Basal cell carcinoma
basic research/science
Biomarkers, Tumor - genetics
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
complication: malignant
dermatology
Female
Follow-Up Studies
Genetic diversity
genetics
Genome-wide association studies
Genome-Wide Association Study
Genomics
Health risk assessment
Humans
Incidence
Kidney Failure, Chronic - surgery
Kidney transplantation
Kidney Transplantation - adverse effects
kidney transplantation/nephrology
Kidney transplants
Male
Melanoma
Middle Aged
Polymorphism, Single Nucleotide
Postoperative Complications - diagnosis
Postoperative Complications - epidemiology
Postoperative Complications - etiology
Prognosis
risk assessment/risk stratification
Risk Factors
side effects
Skin cancer
Skin Neoplasms - diagnosis
Skin Neoplasms - epidemiology
Skin Neoplasms - etiology
Squamous cell carcinoma
Transplant Recipients
United States - epidemiology
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Summary: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. Polygenic risk score of nontransplant non‐melanoma skin cancer is predictive of case:control status and time to non‐melanoma posttransplant, demonstrating the use of genomics to stratify patients at risk for transplant complications.
ISSN:1600-6135
1600-6143
1600-6143
DOI:10.1111/ajt.15057