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Journal of the American Academy of Dermatology
Volume 74, n° 6
page 1144 (juin 2016)
Doi : 10.1016/j.jaad.2015.12.044
accepted : 24 December 2015
Original Articles

High azathioprine dose and lip cancer risk in liver, heart, and lung transplant recipients: A population-based cohort study

Renhua Na, PhD a, Maarit A. Laaksonen, PhD a, b, Andrew E. Grulich, PhD c, Nicola S. Meagher, MPH a, Geoffrey W. McCaughan, PhD d, Anne M. Keogh, PhD e, Claire M. Vajdic, PhD a, b,
a Adult Cancer Program, Lowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia 
b Center for Big Data Research in Health, University of New South Wales, Sydney, Australia 
c Kirby Institute, University of New South Wales, Sydney, Australia 
d Centenary Research Institute, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia 
e St Vincent's Hospital, Sydney, Australia 

Reprint requests: Claire M. Vajdic, PhD, Center for Big Data Research in Health, University of New South Wales, Level 1, Australian Graduate School of Management Bldg, Sydney, NSW 2052 Australia.Center for Big Data Research in HealthUniversity of New South WalesLevel 1Australian Graduate School of Management BldgSydneyNSW 2052Australia

Iatrogenic immunosuppression is a risk factor for lip cancer but the determinants are unknown.


We sought to quantify the association between the type, dose, and duration of iatrogenic immunosuppression and lip cancer risk in solid organ transplant recipients.


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.


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).


Data on potential confounders such as personal solar ultraviolet radiation exposure were not available.


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.

The full text of this article is available in PDF format.

Key words : azathioprine, cohort, immunosuppression, lip cancer, risk factor, squamous cell carcinoma, transplantation

Abbreviations used : CI, HPV, HR, NMSC, SCC, UV, UVR

 Funded by the National Health and Medical Research Council (ID510254; ID568819 to Dr Grulich; ID1053642 to Dr Laaksonen; ID1023159 to Dr Vajdic) and a Cancer Institute New South Wales Career Development Fellowship (ID10/CDF/2-42 to Dr Vajdic) and Early Career Fellowship (ID13/ECF/1-07 to Dr Laaksonen). Dr Na was supported by a Translational Cancer Research Network (TCRN) PhD Scholarship Top-up Award. The TCRN is a translational cancer research center program funded by Cancer Institute New South Wales. The funding bodies played no role in the conduct of the study.
 Conflicts of interest: None declared.

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