TY - JOUR
T1 - Skin cancer in organ transplant recipients
T2 - More than the immune system
AU - Wheless, Lee
AU - Jacks, Sarah
AU - Mooneyham Potter, Kathryn Anne
AU - Leach, Brian C.
AU - Cook, Joel
N1 - Funding Information:
Supported by funding from the National Institutes of Health National Institute of General Medical Sciences grant T32GM008716 (Dr Wheless).
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - calcineurin inhibitors
KW - immunosuppression
KW - mammalian target of rapamycin inhibitors
KW - oncogenic viruses
KW - organ transplant recipients
KW - skin cancer
UR - http://www.scopus.com/inward/record.url?scp=84904743986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904743986&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2014.02.039
DO - 10.1016/j.jaad.2014.02.039
M3 - Review article
C2 - 24725477
AN - SCOPUS:84904743986
SN - 0190-9622
VL - 71
SP - 359
EP - 365
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 2
ER -