title: Skin cancer in organ transplant recipients: more than the immune system.
abstract: Organ transplant recipients (OTRs) are at increased risk of developing nonmelanoma skin cancers. This has long been thought to be caused by immunosuppression and viral infection. However, skin cancer risk among individuals with AIDS or iatrogenic immunodeficiency does not approach the levels seen in OTRs, suggesting other factors play a critical role in oncogenesis. In clinical trials of OTRs, switching from calcineurin inhibitors to mammalian target of rapamycin inhibitors consistently led to a significant reduction in the risk of developing new skin cancers. New evidence suggests calcineurin inhibitors interfere with p53 signaling and nucleotide excision repair. These two pathways are associated with nonmelanoma skin cancer, and squamous cell carcinoma in particular. This finding may help explain the predominance of squamous cell carcinoma over basal cell carcinoma in this population. Mammalian target of rapamycin inhibitors do not appear to impact these pathways. Immunosuppression, viral infection, and impaired DNA repair and p53 signaling all interact in OTRs to create a phenotype of extreme risk for nonmelanoma skin cancer.
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina; Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Lee
authors.initials: L
authors.lastname: Wheless
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jacks
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Kathryn Anne
authors.initials: KA
authors.lastname: Mooneyham Potter
authors.affiliation: Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina. Electronic address: leachb@musc.edu.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Leach
authors.affiliation: Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Joel
authors.initials: J
authors.lastname: Cook
mesh_terms: D065095:Calcineurin Inhibitors; D002280:Basal Cell Carcinoma / Q000209:etiology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016377:Organ Transplantation; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000209:etiology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016159:Tumor Suppressor Protein p53; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: calcineurin inhibitors; immunosuppression; mammalian target of rapamycin inhibitors; oncogenic viruses; organ transplant recipients; skin cancer
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