Díaz-Villamarín, X.; Martínez-Pérez, M.; Nieto-Sánchez, M.T.; Ruiz-Tueros, G.; Fernández-Varón, E.; Torres-García, A.; González Astorga, B.; Blancas, I.; Iáñez, A.J.; Cabeza-Barrera, J.; Morón, R. Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study. Pharmaceutics2024, 16, 956.
Díaz-Villamarín, X.; Martínez-Pérez, M.; Nieto-Sánchez, M.T.; Ruiz-Tueros, G.; Fernández-Varón, E.; Torres-García, A.; González Astorga, B.; Blancas, I.; Iáñez, A.J.; Cabeza-Barrera, J.; Morón, R. Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study. Pharmaceutics 2024, 16, 956.
Díaz-Villamarín, X.; Martínez-Pérez, M.; Nieto-Sánchez, M.T.; Ruiz-Tueros, G.; Fernández-Varón, E.; Torres-García, A.; González Astorga, B.; Blancas, I.; Iáñez, A.J.; Cabeza-Barrera, J.; Morón, R. Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study. Pharmaceutics2024, 16, 956.
Díaz-Villamarín, X.; Martínez-Pérez, M.; Nieto-Sánchez, M.T.; Ruiz-Tueros, G.; Fernández-Varón, E.; Torres-García, A.; González Astorga, B.; Blancas, I.; Iáñez, A.J.; Cabeza-Barrera, J.; Morón, R. Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study. Pharmaceutics 2024, 16, 956.
Abstract
Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798, had shown the highest level of evidence about their association with FPs response. The EMA and FDA-approved drug labels for FPs, recommend genotyping these variants before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still find patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the association with the response to FPs of DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595; as explanatory candidates of the interindividual differences for the FP-related toxicities. We also studied the impact of DPYD*2A, *13, *HapB3, and rs67376798 genotype for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found that FP dose lowering based on DPYD genotype does not affect the treatment efficacy. Also, the DPYD*4 (defined by rs1801158) allele was associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R.= 5.66; 95% C.I.= 1.35 – 23.67; p= 0.014) and multivariate analyses (O.R.= 5.73; 95% C.I.= 1.41 – 28.77; p= 0.019). This makes it a candidate variant for implementation in clinical practice.
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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