Ultrarapid metabolic CYP2C19 *17 allele is associated with squamous cell carcinoma (SCC) risk and increases the association between exposure to voriconazole, an antifungal, and SCC, according to a research letter published in JAMA Dermatology.1
Voriconazole, which is often used in organ transplant recipients, is associated with 73% elevated risk for cutaneous SCC development in lung transplant recipients. The drug is primarily metabolized into voriconazole-N-oxide (VNO), which may play a key role in DNA damage resulting in SCC, by cytochrome P450 enzymes, predominantly CYP2C19.
Individuals may have different CYP2C19 genotypes, making them poor metabolizers or ultrarapid metabolizers of drugs that are metabolized by the CYP2C19 enzyme.
The ultrarapid-metabolizing *17 allele of CYP2C19, which is common in Europeans and Africans and rare in Asians, results in higher circulating concentrations of VNO. Therefore, researchers sought to assess whether lung transplant recipients with *17 allele would have an increased risk for voriconazole-associated SCC.
For the study, researchers analyzed data from 177 lung transplant recipients using genomic DNA and outcome data. Of those, 39% had the *1/*1 genotype that metabolizes at the normal rate, 18.6% had *1/*2 that metabolizes at a slower rate, and 6.2% had the *17/*17 genotype.
Results showed that patients with the *17 allele had a 74% (95% CI, 1.06 – 2.84; P = .03) increased risk for developing SCC. Furthermore, researchers found that the *17 allele was a modifier for SCC risk associated with any exposure to voriconazole.
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However, the authors noted that this study was underpowered for adjustment for male sex, white race, and age older than 50 years at transplantation.
- Williams K, Arron ST. Association of CYP2C19 *17/*17 genotype with the risk of voriconazole-associated squamous cell carcinoma [published online ahead of print March 16, 2016]. JAMA Dermatol. doi: 10.1001/jamadermatol.2016.0351.