., International Genetics and Translational Research in Transplantation Network

McKnight, Amy

Stapleton, Caragh

BackgroundMultiple 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.MethodsPost-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.ResultsSCC 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 (Pc) =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, Pc = 0.02) and BCC status (OR = 7.6, Pc = 0.02). SCC PRS pT 1x10-5 was also a significant predictor of time to post-transplant BCC (Pc = 0.007, HR = 1.8) and SCC (Pc = 0.05, HR = 1.4).ConclusionPRS 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.Oral presentation: CP. Stapleton1,2, KA. Birdwell2, PB. Mark2, ML. Sanders2, PJ. Phelan2, P. Maxwell2, AJ. McKnight2, C. Kennedy2, A. Jardine2, J. Traynor2, F. Chapman2, B. Keating2, PJ. Conlon2 and GL. Cavalleri, iGeneTrain Consortiu

Polygenic risk score as a determinant risk of non-melanoma skin cancer post-kidney transplantation

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