Glutathione S-transferase polymorphisms and skin cancer after renal transplantation

Abstract

Background. Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may also predispose to skin cancer. The glutathione S-transferase enzymes play a major role in limiting the toxic effects of reactive oxygen species, and this study was designed to determine whether polymorphisms in these enzymes are associated with skin cancers in renal transplant recipients. Methods. Two hundred twenty-two long-term survivors of renal transplantation were examined for polymorphisms in the GSTM1, GSTT1, and GSTP1 genes, using a unified polymerase chain reaction with sequence specific primers (PCR-SSP) geno-typing method. Results. The GSTP1*C allele was associated with the development of squamous cell carcinomas (SCCs; P = 0.01). No associations of the GSTM1 null genotype or the GSTT1 null genotype were identified, and the development of basal cell carcinomas was not associated with any GST polymorphism studied. Conclusions. These results indicate that genetic variation in enzymes involved in free radical metabolism in the skin are associated with the development of skin cancer. While all renal transplant recipients should be advised to protect themselves from the sun, the identification of transplant patients with a genetic predisposition to skin tumors may permit the targeting of preventative and early intervention strategies to high-risk individuals.