Skin cancer in renal transplant recipients is associated with increased concentrations of 6-thioguanine nucleotide in red blood cells

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Abstract
Of 108 renal transplant recipients (53 men and 55 women) treated with azathioprine (0.8‐2.9 mg/kg/day) and prednisolone (10 mg daily), 10 men had actinic keratoses, and five of these had squamous cell carcinoma, on light‐exposed areas of skin. The time from transplantation to diagnosis of these skin lesions varied from 1.2 to 9.0 (mean 5.1) years. The concentration of the active azathioprine metabolite 6‐thioguanine nucleotide was 120–425 (mean 276) pmol per 8×108 red blood cells in the transplant patients who developed skin lesions and 54–203 (mean 130) pmol per 8×108 red blood cells in a matched control group of renal transplant recipients. This difference was statistically significant (P=0.005). There was no statistically significant difference between patients and controls in azathioprine dosage, clinical features of immunosuppression, sunlight exposure or infection with human papilloma virus. The association of raised 6‐thioguanine nucleotide concentrations in red blood cells with actinic keratoses and malignant skin tumours in these patinets supports chemical carcinogenesis as a possible cause.