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

Area of Science:

• Pharmacogenomics
• Oncology
• Transplant Medicine

Background:

• Voriconazole is an antifungal medication.
• Voriconazole use is linked to an increased risk of skin cancer.
• The role of individual voriconazole metabolism (CYP2C19 phenotype) in this association is not fully understood.

Purpose of the Study:

• To investigate the association between voriconazole exposure, CYP2C19 metabolizer phenotype, and the development of skin cancer in organ transplant recipients.
• To determine if CYP2C19 phenotype modifies the risk of skin cancer following voriconazole treatment.

Main Methods:

• Retrospective cohort study of 1,739 organ transplant recipients.
• Analysis of voriconazole exposure and CYP2C19 metabolizer status.
• Assessment of the number of skin cancers and time to first skin cancer after treatment.

Main Results:

• A significant association was found between voriconazole exposure, CYP2C19 phenotype, and the number of skin cancers (p < 0.01).
• This association was primarily driven by an increase in squamous cell carcinomas (SCC) among rapid metabolizers exposed to voriconazole (p < 0.01).
• Voriconazole exposure was associated with a faster rate of skin cancer development (Fine-Grey HR 1.78, 95% CI 1.19-2.66), particularly SCC (Fine-Grey HR 1.83, 95% CI 1.14-2.94).

Conclusions:

• Differences in voriconazole metabolism, specifically CYP2C19 phenotype, are significantly associated with an increased number of skin cancers post-transplant.
• Rapid metabolizers exposed to voriconazole face a heightened risk of developing skin cancers, especially SCC.
• These findings highlight the importance of pharmacogenetic considerations in managing voriconazole therapy to mitigate skin cancer risk.