Skin cancer in renal transplant recipients is associated with increased concentrations of 6-thioguanine nucleotide in red blood cells.
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 X 10(8) red blood cells in the transplant patients who developed skin lesions and 54-203 (mean 130) pmol per 8 X 10(8) 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 patients supports chemical carcinogenesis as a possible cause.
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000139:chemically induced; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000032:analysis*; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007642:Keratosis / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood* / Q000139:chemically induced; D013873:Thionucleotides / Q000097:blood*
D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D001379:Azathioprine