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Research Letter |

Association of CYP2C19 *17/*17 Genotype With the Risk of Voriconazole-Associated Squamous Cell Carcinoma

Kiyanna Williams, BS1; Sarah T. Arron, MD, PhD2
[+] Author Affiliations
1Medical student at University of California, San Francisco, School of Medicine
2Department of Dermatology, University of California, San Francisco
JAMA Dermatol. 2016;152(6):719-720. doi:10.1001/jamadermatol.2016.0351.
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This cohort study investigates whether lung transplant recipients with the ultrarapid-metabolizing *17 allele of CYP2C19 have an increased risk for voriconazole-associated cutaneous squamous cell carcinoma.

An estimated 25 767 solid-organ transplantations were performed in 2015.1 Voriconazole, an antifungal used in organ transplant recipients, is associated with a 73% increased risk for cutaneous squamous cell carcinoma (SCC) development in lung transplant recipients (LTRs).2 The mechanism of voriconazole-associated cutaneous malignant neoplasm development is unknown, but the primary metabolite of voriconazole, voriconazole-N-oxide (VNO), is a chromophore for UVB and may play a key role in DNA damage resulting in SCC. Voriconazole is primarily metabolized into VNO by cytochrome P450 enzymes, predominantly CYP2C19 (2-4). Polymorphisms in CYP2C19 affect circulating levels of voriconazole and VNO, with poor metabolizers having 3 to 4 times higher voriconazole plasma concentrations and greater voriconazole to VNO ratios.35 The ultrarapid-metabolizing *17 allele of CYP2C19 (OMIM 124020), which is common in Europeans and Africans and rare in Asians, results in higher circulating concentrations of VNO. We hypothesized that LTRs with the *17 allele would have an increased risk for voriconazole-associated SCC.

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