Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients.
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 (< or =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.
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. anthony.fryer@uhns.nhs.uk
Anthony A
AA
Fryer
Helen M
HM
Ramsay
Tracy J
TJ
Lovatt
Peter W
PW
Jones
Carmel M
CM
Hawley
David L
DL
Nicol
Richard C
RC
Strange
Paul N
PN
Harden
D000328:Adult; D001315:Australia; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D011110:Polymorphism, Genetic; D011239:Prednisolone / Q000009:adverse effects; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D007166:Immunosuppressive Agents; D011239:Prednisolone; D005982:Glutathione Transferase