ArticleRevista da Associacao Medica Brasileira (1992)2026
Genotyping of DPYD and UGT1A1 in Brazilian oncological patients: applying pharmacogenomics in an admixed population.
Article in Revista da Associacao Medica Brasileira (1992), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThe aim of this study was to determine the frequency of UGT1A1 and DPYD polymorphisms among Brazilian patients with gastrointestinal cancer.
methodsUGT1A1 and DPYD polymorphisms were selected due to their importance in the metabolism of fluoropyrimidines and irinotecan, and the existence of available clinical guidelines for dosing recommendations based on genetic testing. Polymorphism rs3918290, rs67376798, rs56038477, rs55886062, rs115232898, and rs887829 were investigated in 100 patients. Allelic discrimination was performed using the TaqMan Assay. Minor allele frequencies were calculated, and metabolic phenotypes were inferred based on the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group guidelines.
resultsFor DPYD, rs56038477 (n=100) showed a minor allele frequency of 1.50% (CI 0.51-4.32), rs115232898 (n=49) had a minor allele frequency of 1.02% (CI 0.18-5.56), and rs3918290 (n=100) had a minor allele frequency of 0.50% (CI 0.09-2.78). No variants were observed in rs67376798 (n=100) or rs55886062 (n=44). A total of 4% of patients received a Clinical Pharmacogenetics Implementation Consortium DPYD activity score (AS) of less than 2.0, with 3% of 1.5 AS and 1% of 0.5 AS. For UGT1A1, rs887829 (n=100) revealed a minor allele frequency of 37.5% (CI 31.09-44.39) and 16% of patients with Dutch Pharmacogenetics Working Group poor metabolizer phenotype.
conclusionThe presence of DPYD and UGT1A1 variants is considerable among Brazilian gastrointestinal cancer patients, reinforcing the promising use of pre-therapeutic genetic tests for irinotecan and fluoropyrimidines to avoid severe toxicities related to treatment. Genetic panels for these variants must be continuously updated and adapted for population-specific characteristics.
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