Polygenic risk score of non‐melanoma skin cancer predicts post‐transplant skin cancer across multiple organ types

Polygenic risk scores (PRS) calculated from genome‐wide association studies (GWAS) of non-melanoma skin cancer (NMSC) in a general, non-transplant setting, have recently been shown to predict risk of, and time to post-renal transplant skin cancer. In this study, we set out to test these findings in a cohort of heart, lung and liver transplant patients to see if these scores could be applied across different organ transplant types. Using the PRS from Stapleton et al. (2018), PRS were calculated for each sample across a European ancestry heart, lung and liver transplant cohorts (n = 523) and tested as predictors time to NMSC post-transplant. The top PRS, squamous cell carcinoma (SCC) pT1x10-5, (n SNPs= 1953), SCC pT1x10-6 and SCC pT1x10-6 (n SNPs = 1061) was significantly predictive in the time to NMSC, SCC and basal cell carcinoma (BCC) analysis across organ (p = 0.006, 0.02 and 0.02 respectively). We observed here a similar direction of effect and effect size [NMSC HR = 1.31(1.08-1.59)] to that in the original, discovery study, with increased polygenic burden leading to a faster time to developing NMSC. In summary, we found that PRS of NMSC calculated from GWAS of NMSC in non-transplant populations independently replicated in this cohort of heart, lung and liver transplant.</p