A series of epidemiological studies are presented of cancer risk after kidney transplantation and in human immunodeficiency virus (HIV) infection, based on data linkage between Australian, nationwide, population-based cohorts of kidney transplant recipients, people with HIV, and cancer. Risk factors were studied for the two most commonly registered cancers after kidney transplantation, lip cancer and non-Hodgkin lymphoma (NHL). The importance of established risk factors for lip cancer was confirmed, including exposure to solar ultraviolet radiation (UVR) and tobacco smoking. New evidence was observed of an association with immunosuppressive agents which potentiate UVR-related cellular damage, which may have broader implications for non-melanoma skin cancer risk in this setting. Clinic-based data suggest that NHL arising early and late after transplantation may be aetiologically distinct. Results observed herein support the possibility of two mechanisms of lymphomagenesis: one predominantly of primary Epstein Barr virus infection during intense immunosuppression and another, of dysregulated lymphoid proliferation in the context of prolonged immunosuppression. Importantly, risk of NHL was observed to persist even ten years after transplantation. For both lip cancer and NHL, risk was significantly reduced on transplant failure and reinstitution of dialysis when immunosuppression is usually ceased. The effect on cancer risk of reduction of immunosuppression was investigated for infection-related and other cancers. Risk was significantly reduced for some other infection- and immunodeficiency-related cancers including Kaposi sarcoma (KS) and melanoma, and non-significantly for anogenital cancers. No effect on risk was observed for cancers of the stomach, leukaemia, or the common epithelial cancers. Risk was significantly higher on reinstitution of dialysis for thyroid cancer. Cancer incidence was examined in HIV infection since the introduction of effective antiretroviral therapy and the reduction in the extent of HIV-related immunosuppression. The patterns observed were entirely consistent with those seen in kidney transplant recipients. Rates of KS, NHL and melanoma declined significantly, whereas rates of anal cancer remained stable. Rates of lung cancer and leukaemia were unchanged. Rates of prostate and colorectal cancers were consistently lower than general population rates. These observations highlight the differential role of current immune function and argue against a generalised effect of immunosurveillance in cancer prevention.
| Identifer | oai:union.ndltd.org:ADTP/258407 |
| Date | January 2009 |
| Creators | van Leeuwen, Marina Theodora, National Centre in HIV Epidemiology & Clinical Research, UNSW |
| Publisher | Publisher:University of New South Wales. National Centre in HIV Epidemiology & Clinical Research |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://unsworks.unsw.edu.au/copyright, http://unsworks.unsw.edu.au/copyright |
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