Voriconazole metabolism is associated with the number of skin cancers per patient.
Cohort study
Epidemiology
Organ transplant
Skin cancer
Study approved as exempt non-human subjects research
VUMC IRB #200335
Voriconazole
Journal
Archives of dermatological research
ISSN: 1432-069X
Titre abrégé: Arch Dermatol Res
Pays: Germany
ID NLM: 8000462
Informations de publication
Date de publication:
31 May 2024
31 May 2024
Historique:
received:
23
03
2024
accepted:
02
05
2024
revised:
29
04
2024
medline:
31
5
2024
pubmed:
31
5
2024
entrez:
31
5
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38819581
doi: 10.1007/s00403-024-03135-5
pii: 10.1007/s00403-024-03135-5
doi:
Substances chimiques
Voriconazole
JFU09I87TR
Antifungal Agents
0
Cytochrome P-450 CYP2C19
EC 1.14.14.1
CYP2C19 protein, human
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
303Subventions
Organisme : CSRD VA
ID : IK2 CX002452
Pays : United States
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Singer JP, Boker A, Metchnikoff C, Binstock M, Boettger R, Golden JA et al (2012) High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients. J Heart Lung Transpl 31:694–699
doi: 10.1016/j.healun.2012.02.033
Williams K, Mansh M, Chin-Hong P, Singer J, Arron ST (2013) Voriconazole-Associated Cutaneous Malignancy: A literature review on Photocarcinogenesis in Organ Transplant recipients. Clin Infect Dis 58:997–1002
doi: 10.1093/cid/cit940
pubmed: 24363331
pmcid: 6276938
Kuklinski LF, Li S, Karagas MR, Weng W-K, Kwong BY (2017) Effect of voriconazole on risk of nonmelanoma skin cancer after hematopoietic cell transplantation. J Am Acad Dermatol 77:706–712
doi: 10.1016/j.jaad.2017.06.032
pubmed: 28780363
pmcid: 5877457
D’Arcy ME, Pfeiffer RM, Rivera DR, Hess GP, Cahoon EK, Arron ST et al (2020) Voriconazole and the risk of keratinocyte carcinomas among lung transplant recipients in the United States. JAMA Dermatol 156:772–779
doi: 10.1001/jamadermatol.2020.1141
pubmed: 32401271
Ona K, Oh DH (2015) Voriconazole N-oxide and its ultraviolet B photoproduct sensitize keratinocytes to ultraviolet A. Br J Dermatol 173:751–759
doi: 10.1111/bjd.13862
pubmed: 25919127
Morlière P, Silva AMS, Seixas RSGR, Boscá F, Mazière J-C, Ferreira J et al (2018) Photosensitisation by voriconazole-N-oxide results from a sequence of solvent and pH-dependent photochemical and thermal reactions. J Photochem Photobiol B 187:1–9
doi: 10.1016/j.jphotobiol.2018.07.023
pubmed: 30081214
Moriyama B, Obeng AO, Barbarino J, Penzak SR, Henning SA, Scott SA et al (2017) Clinical pharmacogenetics implementation Consortium (CPIC) Guidelines for CYP2C19 and voriconazole therapy. Clin Pharmacol Ther 102:45–51
doi: 10.1002/cpt.583
pubmed: 27981572
Williams K, Arron ST (2016) Association of CYP2C19 *17/*17 genotype with the risk of Voriconazole-Associated squamous cell carcinoma. JAMA Dermatol 152:719–720
doi: 10.1001/jamadermatol.2016.0351
pubmed: 26982740
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP et al (2007) The strengthening the reporting of Observational studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Epidemiology 18:800–804
doi: 10.1097/EDE.0b013e3181577654
Wheless L, Baker L, Edwards L, Anand N, Birdwell K, Hanlon A et al (2020) Development of phenotyping algorithms for the identification of organ transplant recipients: Cohort Study. JMIR Med Inform [Internet]. https://doi.org/10.2196/18001
Roden DM, Pulley JM, Basford MA, Bernard GR, Clayton EW, Balser JR et al (2008) Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin Pharmacol Ther 84:362–369
doi: 10.1038/clpt.2008.89
pubmed: 18500243
Lee S-B, Wheeler MM, Patterson K, McGee S, Dalton R, Woodahl EL et al (2019) Stargazer: a software tool for calling star alleles from next-generation sequencing data using CYP2D6 as a model. Genet Med 21:361–372
doi: 10.1038/s41436-018-0054-0
pubmed: 29875422
Lee S-B, Wheeler MM, Thummel KE, Nickerson DA (2019) Calling star alleles with stargazer in 28 pharmacogenes with whole genome sequences. Clin Pharmacol Ther 106:1328–1337
doi: 10.1002/cpt.1552
pubmed: 31206625
pmcid: 6896231
Anand N, Edwards L, Baker LX, Chren M-M, Wheless L (2021) Validity of Using Billing Codes From Electronic Health Records to Estimate Skin Cancer Counts. JAMA Dermatol [Internet]. https://doi.org/10.1001/jamadermatol.2021.2856
Scrucca L, Santucci A, Aversa F (2010) Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transpl 45:1388–1395
doi: 10.1038/bmt.2009.359
Jiyad Z, Olsen CM, Burke MT, Isbel NM, Green AC (2016) Azathioprine and risk of skin Cancer in Organ Transplant recipients: systematic review and Meta-analysis. Am J Transpl 16:3490–3503
doi: 10.1111/ajt.13863
Wheless L, Anand N, Hanlon A, Chren M-M (2022) Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients. JAMA Dermatol [Internet]. https://doi.org/10.1001/jamadermatol.2022.3878
Kreher MA, Noland MMB, Konda S, Longo MI, Valdes-Rodriguez R (2023) Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids. J Am Acad Dermatol 88:521–530
doi: 10.1016/j.jaad.2022.11.044
pubmed: 36460257
Mansh M, Binstock M, Williams K, Hafeez F, Kim J, Glidden D et al (2016) Voriconazole exposure and risk of cutaneous squamous cell carcinoma, aspergillus colonization, invasive aspergillosis and death in lung transplant recipients. Am J Transpl 16:262–270
doi: 10.1111/ajt.13431
Li B, Sangkuhl K, Whaley R, Woon M, Keat K, Whirl-Carrillo M et al (2023) Frequencies of pharmacogenomic alleles across biogeographic groups in a large-scale biobank. Am J Hum Genet 110:1628–1647
doi: 10.1016/j.ajhg.2023.09.001
pubmed: 37757824
pmcid: 10577080
Douglas AP, Smibert OC, Bajel A, Halliday CL, Lavee O, McMullan B et al (2021) Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021. Intern Med J 51(Suppl 7):143–176
doi: 10.1111/imj.15591
pubmed: 34937136
Dolton MJ, Ray JE, Chen SC-A, Ng K, Pont LG, McLachlan AJ (2012) Multicenter study of voriconazole pharmacokinetics and therapeutic drug monitoring. Antimicrob Agents Chemother 56:4793–4799
doi: 10.1128/AAC.00626-12
pubmed: 22751544
pmcid: 3421881
Kuschal C, Thoms K-M, Schubert S, Schäfer A, Boeckmann L, Schön MP et al (2012) Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair. Exp Dermatol 21:2–6
doi: 10.1111/j.1600-0625.2011.01413.x
pubmed: 22151386
Niwa T, Imagawa Y, Yamazaki H (2014) Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr Drug Metab 15:651–679
doi: 10.2174/1389200215666141125121511
pubmed: 25429674