title: Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy.
abstract: BACKGROUND
  The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial.
  
  
  RESULTS
  We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC.
  
  
  CONCLUSIONS
  Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.
authors.affiliation: Department of Cardiology, University of Padova, Padova, Italy. acaforio@ux1.unipd.it
authors.forename: A L
authors.initials: AL
authors.lastname: Caforio
authors.forename: A B
authors.initials: AB
authors.lastname: Fortina
authors.forename: S
authors.initials: S
authors.lastname: Piaserico
authors.forename: M
authors.initials: M
authors.lastname: Alaibac
authors.forename: F
authors.initials: F
authors.lastname: Tona
authors.forename: G
authors.initials: G
authors.lastname: Feltrin
authors.forename: E
authors.initials: E
authors.lastname: Pompei
authors.forename: L
authors.initials: L
authors.lastname: Testolin
authors.forename: A
authors.initials: A
authors.lastname: Gambino
authors.forename: S D
authors.initials: SD
authors.lastname: Volta
authors.forename: G
authors.initials: G
authors.lastname: Thiene
authors.forename: D
authors.initials: D
authors.lastname: Casarotto
authors.forename: A
authors.initials: A
authors.lastname: Peserico
mesh_terms: D017677:Age Distribution; D001379:Azathioprine / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D015897:Comorbidity; D016572:Cyclosporine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007642:Keratosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D012880:Skin Pigmentation; D013472:Sunlight / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone