Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis

Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase ( ) gene encodes DPD, and studies suggest that polymorphisms can result in...

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Veröffentlicht in:Journal of personalized medicine 2022-02, Vol.12 (2), p.225
Hauptverfasser: Kim, Woorim, Cho, Young-Ah, Kim, Dong-Chul, Lee, Kyung-Eun
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Cho, Young-Ah
Kim, Dong-Chul
Lee, Kyung-Eun
description Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase ( ) gene encodes DPD, and studies suggest that polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with rs1801160 polymorphism. We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity. The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83). rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. Therefore, rs1801160 can be a potential candidate for DPD deficiency screening prior to fluoropyrimidine-based regimen.
doi_str_mv 10.3390/jpm12020225
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The dihydropyrimidine dehydrogenase ( ) gene encodes DPD, and studies suggest that polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with rs1801160 polymorphism. We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity. The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83). rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. 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subjects Alleles
Bias
Cancer
Dehydrogenases
Diarrhea
Gene polymorphism
Genotype & phenotype
Hematology
Literature reviews
Meta-analysis
Metabolism
Metabolites
Neutropenia
Patients
Polymorphism
Precision medicine
Sensitivity analysis
Toxicity
title Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis
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