Purpose: It has been consistently shown that lip cancer occurs at markedly increased rates following renal transplantation. However, epidemiological studies are few and lip cancer etiology, either in the context of immune deficiency or in the general population, remains poorly understood. This study aims to examine risk factors for lip cancer in a large, population-based, Australian cohort of renal transplant recipients.
 Methods: Diagnoses of lip cancer in a cohort of 8,162 renal transplant recipients during 1982 - 2002 were ascertained through probabilistic data linkage between the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and the National Cancer Statistics Clearing House (NCSCH). All cancers within the lip rubric (ICD10 C00) were included; cancers of the skin of lip (ICD10 C43, C44) were excluded. Person-years of follow-up were accrued from the date of transplantation until the first diagnosis of lip cancer, death, or last contact. Multivariate Poisson regression was used to assess risk for all lip cancer during periods of transplantation and subsequent dialysis, as well as risk factors for squamous cell cancer (SCC) of the lower lip vermillion during the period following first transplantation only.
 Results: 203 diagnoses of lip cancer were recorded, with incidence approximately 10-fold higher during periods of transplantation than during periods of dialysis after transplant failure. In multivariate analysis, risk factors for SCC of the lower lip vermillion (n=121) included older age (p<0.001), male sex (p<0.001), Australian country of birth (p=0.012), greater time since transplantation (p=0.001), current use of Azathioprine (p<0.001), increasing years of prior dialysis (p=0.030), and non-receipt of antibodies (p=0.037). An association with latitude was observed (p=0.042), though it was non-linear. History of smoking was of borderline significance (p=0.050), as was current use of Cyclosporine (p=0.064).
 Conclusion: Lip cancer risk following renal transplantation appears largely driven by the interaction between immunosuppressive agents and sun exposure. Current receipt of Azathioprine, thought to increase UVA photosensitivity, and Cyclosporine, which inhibits DNA repair mechanisms, may indicate increased potential for UV-related cellular damage and malignancy. The fact that lip cancer risk was confined almost entirely to periods of transplantation supports a role for the currency of receipt of immunosuppressive agents. This finding may also inform the high risk for non-melanoma skin cancer widely documented in this group. Interestingly, time since transplantation, an indicator of the duration of receipt of immunosuppressive agents, also remained statistically significant. This may suggest an independent role for immunodeficiency in lip cancer etiology, which is consistent with the increased risk for lip cancer observed in other immune-deficient populations, such as those with HIV/AIDS.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA