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Abstract
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 (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).
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.
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 Consortium
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 (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).
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.
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 Consortium
| Original language | English |
|---|---|
| Pages | 32 |
| Publication status | Published - 01 Oct 2017 |
| Event | American Society of Nephrology 2017 conference - New Orleans, United States Duration: 01 Nov 2017 → 05 Nov 2017 |
Conference
| Conference | American Society of Nephrology 2017 conference |
|---|---|
| Abbreviated title | ASN |
| Country/Territory | United States |
| City | New Orleans |
| Period | 01/11/2017 → 05/11/2017 |
Bibliographical note
Journal of the American Society of Nephrology - Nov 2017 issueKeywords
- kidney disease
- SNP
- GWAS
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