title: Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients.
abstract: BACKGROUND
  Cutaneous squamous cell carcinoma (cSCC) occurs with higher frequency and recurrence rates, increased morbidity and mortality, and more aggressive metastasis in kidney and heart transplant recipients compared to the general population but all transplant recipients do not develop cSCC. In addition, the phenotypic expression of cSCC among transplant recipients can vary between mild disease to extensive recurrent metastatic disease. These clinically observed differences in occurrence and severity of cSCC among transplant recipients suggest the possibility that an underlying genetic component might modify risk.
  
  
  METHODS
  We identified 88 white post-transplant cSCC cases (71 kidney and 17 heart) and 300 white post-transplant controls (265 kidney and 35 heart) using a DNA biobank linked with de-identified electronic medical records. Logistic regression was used to determine adjusted odds ratios (OR) for clinical characteristics and single nucleotide polymorphisms (SNP) associated with cSCC in both a candidate SNP and genome wide analysis.
  
  
  RESULTS
  Age (OR 1.08 [1.05-1.11], p<0.001) and azathioprine exposure (OR 8.64 [3.92-19.03], p<0.001) were significantly associated while gender, smoking tobacco use, dialysis duration and immunosuppression duration were not. Ten candidate SNPs previously associated with non-melanoma skin cancer in the general population were significantly associated with cSCC in transplant recipients. Genome wide association analysis implicated SNPs in genes previously associated with malignancy,CSMD1(OR 3.14 [1.90-5.20]) andCACNA1D(OR 2.67 [1.73-4.10]).
  
  
  CONCLUSIONS
  This study shows an association of increasing age and azathioprine exposure with cSCC and confirms a genetic contribution for cSCC development in kidney and heart transplant recipients.
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: M Lee
authors.initials: ML
authors.lastname: Sanders
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Karnes
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Josh C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Birdwell