Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients

M Lee Sanders; Jason H Karnes; Josh C Denny; Dan M Roden; T Alp Ikizler; Kelly A Birdwell

doi:10.1097/TXD.0000000000000521

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Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients

Journal article

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Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients

M Lee Sanders, Jason H Karnes, Josh C Denny, Dan M Roden, T Alp Ikizler and Kelly A Birdwell

Transplantation direct, Vol.1(4), pp.1-7

05/2015

DOI: 10.1097/TXD.0000000000000521

PMCID: PMC4486315

PMID: 26146661

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Abstract

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. 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. 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, (OR 3.14 [1.90-5.20]) and (OR 2.67 [1.73-4.10]). 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.

Details

Title: Subtitle: Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients
Creators: M Lee Sanders - Vanderbilt University Medical Center, Nashville, TN, USA
Jason H Karnes - Vanderbilt University Medical Center, Nashville, TN, USA
Josh C Denny - Vanderbilt University Medical Center, Nashville, TN, USA
Dan M Roden - Vanderbilt University Medical Center, Nashville, TN, USA
T Alp Ikizler - Vanderbilt University Medical Center, Nashville, TN, USA
Kelly A Birdwell - Vanderbilt University Medical Center, Nashville, TN, USA
Resource Type: Journal article
Publication Details: Transplantation direct, Vol.1(4), pp.1-7
DOI: 10.1097/TXD.0000000000000521
PMID: 26146661
PMCID: PMC4486315
NLM abbreviation: Transplant Direct
ISSN: 2373-8731
eISSN: 2373-8731
Grant note: RC2 GM092618 / NIGMS NIH HHS T32 GM007569 / NIGMS NIH HHS K23 GM100183 / NIGMS NIH HHS T32 DK007569 / NIDDK NIH HHS K24 DK062849 / NIDDK NIH HHS U01 HG004603 / NHGRI NIH HHS UL1 TR000445 / NCATS NIH HHS
Language: English
Date published: 05/2015
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094733702771

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