Voriconazole metabolism is associated with the number of skin cancers per patient

• Published in: Archives of Dermatological Research Vol. 316; no. 6; p. 303
• Main Authors: Ike, Jacqueline I., Smith, Isabelle T., Mosley, Dominique, Madden, Christopher, Grossarth, Sarah, Halle, Briana R., Lewis, Adam, Mentch, Frank, Hakonarson, Hakon, Bastarache, Lisa, Wheless, Lee
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 31.05.2024; Springer Nature B.V
• Subjects: Adult; Aged; Antifungal agents; Antifungal Agents - adverse effects; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - metabolism; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2C19 - metabolism; Dermatology; Female; Humans; Male; Medicine; Medicine & Public Health; Metabolism; Middle Aged; Organ Transplantation - adverse effects; Original Paper; Phenotypes; Phenotypic variations; Retrospective Studies; Skin cancer; Skin Neoplasms - epidemiology; Skin Neoplasms - etiology; Skin Neoplasms - metabolism; Squamous cell carcinoma; Voriconazole; Voriconazole - adverse effects; Organ transplant; Study approved as exempt non-human subjects research; Cohort study; Voriconazole; VUMC IRB #200335; Epidemiology; Skin cancer
• ISSN: 1432-069X; 0340-3696; 1432-069X
• DOI: 10.1007/s00403-024-03135-5

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two ( p  < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure ( p  < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19–2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14–2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.