ArticleClinical pharmacology and therapeutics2017
Novel Deleterious Dihydropyrimidine Dehydrogenase Variants May Contribute to 5-Fluorouracil Sensitivity in an East African Population.
Article in Clinical pharmacology and therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- DPYD genetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: a systematic review.British journal of cancer · 2024Pooled it
- Dihydropyrimidine Dehydrogenase Genotype-Phenotype Correlations in Plasma and Peripheral Blood Mononuclear Cells.Clinical pharmacology and therapeutics · 2026Article
- Potential clinical relevance of rare dihydropyrimidine dehydrogenase genetic variants identified using whole-exome NextGen sequencing in cancer patients with severe fluoropyrimidine toxicity.Cancer chemotherapy and pharmacology · 2025Article
- Pharmacogenetic Profiling of Genes Associated with Outcomes of Chemotherapy in Omani Healthy Controls.Genes · 2025Article
- The Frequency ofPharmaceutics · 2024Article
- Lethal 5-Fluorouracil Toxicity in a Carrier ofJCO precision oncology · 2024Article
- Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD.Genome medicine · 2024Article
- Implementation of pharmacogenetic testing in oncology:Frontiers in pharmacology · 2023Article
- Introducing a simple and cost-effective RT-PCR protocol for detection of DPYD*2A polymorphism: the first study in Kurdish population.Cancer chemotherapy and pharmacology · 2022Article
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- Testing for Dihydropyrimidine Dehydrogenase Deficiency to Individualize 5-Fluorouracil Therapy.Cancers · 2022Review
- Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health.Human genetics · 2022Review
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- Importance of RareFrontiers in pharmacology · 2022Article
- Evaluation of population-level pharmacogenetic actionability in Alabama.Clinical and translational science · 2021Article
- Individualized Dosing of Fluoropyrimidine-Based Chemotherapy to Prevent Severe Fluoropyrimidine-Related Toxicity: What Are the Options?Clinical pharmacology and therapeutics · 2021Review
- Ethnic Diversity of DPD Activity and thePharmacogenomics and personalized medicine · 2021Review
- Population-scale predictions of DPD and TPMT phenotypes using a quantitative pharmacogene-specific ensemble classifier.British journal of cancer · 2020Article
- In Vitro Assessment of Fluoropyrimidine-Metabolizing Enzymes: Dihydropyrimidine Dehydrogenase, Dihydropyrimidinase, and β-Ureidopropionase.Journal of clinical medicine · 2020Review
- Implementation of pharmacogenomic testing in oncology care (PhOCus): study protocol of a pragmatic, randomized clinical trial.Therapeutic advances in medical oncology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Clinical studies have identified specific genetic variants in dihydropyrimidine dehydrogenase (DPD; DPYD gene) as predictors of severe adverse toxicity to the commonly used chemotherapeutic 5-fluorouracil (5-FU); however, these studies have focused on European and European-American populations. Our laboratory recently demonstrated that additional variants in non-European haplotypes are predictive of 5-FU toxicity. The objective of this study was to identify potential risk variants in an understudied East African population relevant to our institution's catchment area. The DPYD protein-coding region was sequenced in 588 individuals of Somali or Kenyan ancestry living in central/southeast Minnesota. Twelve novel nonsynonymous variants were identified, seven of which significantly decreased DPD activity in vitro. The commonly reported toxicity-associated variants, *2A, D949V, and I560S, were not detected in any individuals. Overall, this study demonstrates a critical limitation in our knowledge of pharmacogenetic predictors of 5-FU toxicity, which has been based on clinical studies conducted in populations of limited diversity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.