Carcinogenesis Advance Access originally published online on September 30, 2004
Carcinogenesis 2005 26(1):185-191; doi:10.1093/carcin/bgh291
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Carcinogenesis vol.26 no.1 © Oxford University Press 2005; all rights reserved.
ARTICLE |
Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients
1 Human Genomics Research Group, Institute for Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, UK, 2 Department of Dermatology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, UK, 3 Department of Mathematics, Keele University, Keele, Staffordshire, UK, 4 Renal Transplant Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia and 5 Department of Renal Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, UK
6 To whom correspondence should be addressed Email: anthony.fryer{at}uhns.nhs.uk
Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associated with NMSC in UK recipients. However, the effect of high UVR exposure and differences in immunosuppressive regimen on these associations is unknown. In this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361 Queensland renal transplant recipients. Data on squamous (SCC) and basal cell carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations with both NMSC risk and numbers were examined using logistic and negative binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer SCC. Recipients were then stratified by prednisolone dose (
7 versus >7 mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1 Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR = 2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group. GSTP1 associations were strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK findings, suggesting that protection against UVR-induced oxidative stress is important in NMSC development in recipients, but that this effect depends on the immunosuppressant regimen.
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