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Detection of relevant pharmacogenetic information through exome sequencing in oncology.

Simon VerdezJuliette AlbuissonYannis DuffourdRomain BoidotManon RedaChristel Thauvin-RobinetJean-David FumetSylvain LadoireSophie NambotPatrick CallierLaurence FaivreFrançois GhiringhelliNicolas Picard
Published in: Pharmacogenomics (2022)
Background: Germline sequencing of individual genomes can detect alleles responsible for adverse drug reactions (ADRs) in relation to chemotherapy, targeted agents, antiemetics or pain treatment. Materials & methods: To evaluate the interest of such pharmacogenetic information, the authors retrospectively analyzed genes known to have an impact on cancer therapy in a cohort of 445 solid cancers patients. Results: Six patients treated with 5-fluorouracil carrying one DPYD variant classified as 1A showed decreased drug mean clearance (p = 0.01). Regarding CYP2D6 , all patients (n = 5) with predicted CYP2D6 poor or ultra-rapid metabolizer status experienced adverse drug reactions related to opioid therapy. Conclusion: Genomic germline sequencing performed for theragnostic issues in patients with a solid tumor, can provide relevant information about common pharmacogenetic alleles.
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