Incidence and risk factors for cancer after liver, heart and lung transplantation in Australia

Abstract

Background: Iatrogenic immunosuppression increases the risk of cancer after solid organ transplantation, but little is known about the site-specific risk of cancer in non-kidney transplant recipients, or the features of immunosuppressive therapy responsible for cancer occurrence. Methods: I conducted a population-based cohort study of Australian liver, heart and lung transplant recipients (1984-2006) and ascertained deaths and incident cancers by record linkage. I collected comprehensive longitudinal clinical data, including the type and dose of immunosuppression, from 18 transplant units. I estimated the site-specific risk of cancer and cancer-related mortality in transplant recipients relative to the general population. I quantified the type and dose of individual immunosuppressive agents by time since transplantation and organ type. I examined the association between the type, dose and duration of immunosuppression and risk of the two most common cancers, non-Hodgkin lymphoma (NHL) and lip cancer, accounting for competing risk of death. Results: I observed an excess risk for sixteen cancer types, predominantly cancers with a viral cause. Overall the cancer risk profile was similar by organ type, but notable exceptions suggested a role for organ-specific pre-existing diseases, carcinogenic behaviours, and differences in the extent of immunosuppression. Risk of de novo cancer-related mortality was significantly elevated and as expected the profile mirrored that for cancer incidence. I observed significant changes in the type and dose of individual immunosuppressive agents by time since transplantation, transplant era, and organ type. I found that a high dose of azathioprine was independently associated with a moderate dose-related risk of NHL and lip cancer. I showed that differences in the risk of NHL and lip cancer by organ type are attributed to differences in the dose of immunosuppression. I confirmed the increased risk of early NHL with use of muromonab-CD3 induction antibody, the increased risk of late NHL and lip cancer with both increasing duration of immunosuppression and increasing age, and the increased risk of lip cancer with smoking. Earlier transplant era also increased lip cancer risk. Conclusions: The type, dose (extent) and duration of iatrogenic immunosuppression contribute to the excess risk of cancer in liver, heart and lung transplant recipients.