Kidney Week

Abstract: TH-OR120

Polygenic Risk Score as a Determinant of Risk of Non-Melanoma Skin Cancer Post-Renal Transplantation

Session Information

• Transplantation: Top 10 Basic and Experimental Abstracts
  November 02, 2017 | Location: Room 295, Morial Convention Center
  Abstract Time: 04:54 PM - 05:06 PM

Category: Transplantation

• 1701 Transplantation: Basic and Experimental

Authors

• Stapleton, Caragh P., Royal College of Surgeons, Dublin, Ireland

Caragh P. Stapleton



Caragh Stapleton is a PhD candidate in the Department of Molecular and Cellular Therapeutics in the Royal College of Surgeons in Ireland. Her research interest is in the area of human and statistical genetics with a particular interest in renal and transplant genetics. More specifically, her work focuses on the area of genomics of transplant outcomes and complications including allograft function and post-transplant skin cancer.

• Birdwell, Kelly A., Vanderbilt University, Nashville, Tennessee, United States

Kelly A. Birdwell,

• Mark, Patrick B., University of Glasgow, Glasgow, United Kingdom

Patrick B. Mark,

• Sanders, M. Lee, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States

M. Lee Sanders,

• Phelan, Paul J., Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom

Paul J. Phelan,

• Maxwell, Alexander P., Queen's University Belfast, Belfast, United Kingdom

Alexander P. Maxwell,

• McKnight, A.J., Queen's University Belfast, Belfast, United Kingdom

A.J. McKnight,

• Kennedy, Claire, Beaumont Hospital, Dublin 9, Dublin, Ireland

Claire Kennedy,

• Jardine, Alan G., University of Glasgow, Glasgow, United Kingdom

Alan G. Jardine,

• Traynor, Jamie P., NHS Greater Glasgow and Clyde, Glasgow, United Kingdom

Jamie P. Traynor,

• Chapman, Fiona A, NHS Scotland, Glasgow, United Kingdom

Fiona A Chapman,

• Keating, Brendan, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Brendan Keating,

• Conlon, Peter J., Beaumont Hospital, Dublin 9, Dublin, Ireland

Peter J. Conlon,

• Cavalleri, Gianpiero, Royal College of Surgeons, Dublin, Ireland

Gianpiero Cavalleri,

Group or Team Name

• International Genetics & Translational Research in Transplantation Network

Background

Multiple genetic loci have been identified for non-melanoma skin cancer (NMSC) in the general population. Polygenic risk score (PRS) was defined as the sum of all alleles associated with a trait weighted by the effect size of that allele as determined by a previous genome-wide association study (GWAS). We tested whether PRS, calculated using a GWAS of NMSC in a non-transplant population, can be used to determine risk of developing and time to NMSC post-kidney transplant.

Methods

Post-kidney transplant NMSC cases (n=155) and controls (n=442) were collected from Tennessee, Ireland and Scotland. Genetic variants that reached pre-defined levels of significance were chosen from a squamous cell carcinoma (SCC), and a basal cell carcinoma (BCC) GWAS, both conducted in non-transplant populations. Using these GWAS results, BCC and SCC PRSs were calculated at each p-value threshold (pT) for each sample in the renal transplant cohorts. PRSs were normalized so mean = 0 and standard deviation = 1. PRSs were tested as a predictor of case: control status in a logistic regression model and time to NMSC post-transplant in a survival model. Age of recipient at transplant, recruitment centre, azathioprine exposure and the first four principal components were included as covariates in both models.

Results

SCC PRS calculated at pT of 1x10^-6 was the most significant predictor of case: control status of NMSC post-transplant (OR per 1 standard deviation increase in PRS = 2.3; corrected P (P_c) =0.04). When we subdivided NMSC into SCC and BCC, SCC PRS pT 1x10^-6 was a significant predictor of case:control SCC (OR = 2.5, P_c = 0.02) and BCC status (OR = 7.6, P_c = 0.02). SCC PRS pT 1x10^-5 was also a significant predictor of time to post-transplant BCC (P_c = 0.007, HR = 1.8) and SCC (P_c = 0.05, HR = 1.4).

Conclusion

PRS of non-transplant NMSC can be used to predict case:control status of post-transplant NMSC, SCC and BCC as well as time to developing BCC and SCC post-transplant.

Funding

• Government Support - Non-U.S.