title: High azathioprine dose and lip cancer risk in liver, heart, and lung transplant recipients: A population-based cohort study.
abstract: BACKGROUND
  Iatrogenic immunosuppression is a risk factor for lip cancer but the determinants are unknown.
  
  
  OBJECTIVE
  We sought to quantify the association between the type, dose, and duration of iatrogenic immunosuppression and lip cancer risk in solid organ transplant recipients.
  
  
  METHODS
  We conducted a population-based cohort study of all adult Australian liver, heart, and lung transplant recipients from 1984 to 2006 (n = 4141). We abstracted longitudinal data from medical records and ascertained incident lip cancer (n = 58) and deaths (n = 1434) by linkage with national registries. We estimated multivariable hazard ratios (HR) for lip cancer using the Fine and Gray proportional subdistribution hazards model, accounting for death as a competing risk.
  
  
  RESULTS
  Lip cancer risk (n = 58) increased with high mean daily dose of azathioprine (HR 2.28, 95% confidence interval [CI] 1.18-4.38), longer duration of immunosuppression (HR 9.86, 95% CI 2.10-46.3), increasing year of age at transplantation (HR 1.14, 95% CI 1.04-1.25), earlier transplantation era (HR 8.73, 95% CI 1.11-68.7), and history of smoking (HR 2.71, 95% CI 1.09-6.70).
  
  
  CONCLUSIONS
  Data on potential confounders such as personal solar ultraviolet radiation exposure were not available.
  
  
  CONCLUSIONS
  Higher doses of azathioprine increase lip cancer risk, with implications for managing immunosuppressed populations and our understanding of the relationship between solar ultraviolet radiation and lip cancer.
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Renhua
authors.initials: R
authors.lastname: Na
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Center for Big Data Research in Health, University of New South Wales, Sydney, Australia.
authors.forename: Maarit A
authors.initials: MA
authors.lastname: Laaksonen
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Grulich
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Meagher
authors.affiliation: Centenary Research Institute, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: St Vincent's Hospital, Sydney, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Keogh
authors.affiliation: Adult Cancer Program, Lowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Center for Big Data Research in Health, University of New South Wales, Sydney, Australia. Electronic address: claire.vajdic@unsw.edu.au.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
mesh_terms: D000328:Adult; D000367:Age Factors; D001315:Australia / Q000453:epidemiology; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000401:mortality; D016027:Heart Transplantation / Q000706:statistics & numerical data*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008048:Lip Neoplasms / Q000453:epidemiology* / Q000401:mortality; D016031:Liver Transplantation / Q000706:statistics & numerical data*; D016040:Lung Transplantation / Q000706:statistics & numerical data*; D008498:Medical Record Linkage; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: azathioprine; cohort; immunosuppression; lip cancer; risk factor; squamous cell carcinoma; transplantation