Clinical and Genetic Predictors of Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients.

Abstract

Background: Cutaneous squamous cell carcinoma (cSCC) occurs more frequently in kidney and heart transplant recipients compared to the general population with more aggressive metastasis, a higher rate of recurrence, and an increased morbidity and mortality. We set out to identify clinical and genetic predictors that confer an increased risk for cSCC in this patient population. Methods: We identified 88 Caucasian post-transplant cSCC cases (71 kidney and 17 heart) and 300 Caucasian controls (265 kidney and 35 heart) using a DNA biobank linked with de-identified electronic medical records (EMR). We attempted to replicate signals for previously identified single nucleotide polymorphisms (SNPs) associated with increased cSCC risk and performed a genome wide association study (GWAS) for cSCC. Logistic regression was used to determine odds ratios (OR) adjusted for clinical predictors and SNP effects in an additive model using SPSS and PLINK. Results: Age (OR 1.09 [1.09-1.11], p<0.0001) and azathioprine exposure (OR 8.52 [3.84-18.88], p<0.0001) were significant clinical predictors of cSCC development while gender, duration of dialysis, duration of immunosuppression, inhaled tobacco use, transplanted organ type, and total number of transplant procedures were not. We replicated signals for rs12210050, a SNP near EXOC2 (OR 2.19, p=0.001) and rs12203592, a SNP in IRF4 (OR 2.11, p=0.005), both previously associated with increased cSCC risk. No SNPs reached genome-wide significance (p<5x10-8) in the GWAS. The top associations were in genes previously associated with malignancy, including rs8065820 in a CpG island in HIC1 (OR 3.93, p=1.1x10-5) and rs17688743 in PRKCA (OR 4.32, p=1.8x10-5). Conclusions: Age, azathioprine exposure, and two SNPs previously associated with increased cSCC risk (rs12210050 and rs12203592) were significant predictors for the development of cSCC in an EMR-based cohort of Caucasian kidney and heart transplant recipients. GWAS analysis suggests a role for the biologically plausible genes HIC1 and PRKCA in cSCC. Replication and further studies are required to confirm these genetic predictors. DISCLOSURES:Ikizler, T.: Other, DSI, Inc., Baxter Renal Care, SatelliteHealth, Consultancy agreement and research funding, AMGEN, Affymax, Abbott Nutrition, Abbott Renal, Consultancy agreement and research funding, Fresenius- Kabi, Consultancy agreement and research funding.