ArticleBritish journal of cancer2020
Population-scale predictions of DPD and TPMT phenotypes using a quantitative pharmacogene-specific ensemble classifier.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- DPYD genetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: a systematic review.British journal of cancer · 2024Pooled it
- Multicenter phase II study of neoadjuvant FOLFOXIRI followed by concurrent chemoradiotherapy in Chinese patients with high-risk rectal cancer.The oncologist · 2026Trial
- Trial
- Carcinogenic Medications: A Review of Specific Agents and Molecular Mechanisms of Carcinogenesis.Cancer reports (Hoboken, N.J.) · 2026Review
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Population frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo.Human genome variation · 2026Article
- Navigating Cardiotoxicity in Cancer Treatment: Insights into Fluoropyrimidine-induced Cardiac Events.Current cardiology reviews · 2026Review
- Opportunities and Challenges of Population Pharmacogenomics.Annals of human genetics · 2025Review
- Translating pharmacogenomic sequencing data into drug response predictions-How to interpret variants of unknown significance.British journal of clinical pharmacology · 2025Review
- Validation of diagnostic screening test for pharmacogenomic targets for thiopurine drugs in indian pediatric acute lymphoblastic leukemia patients.Frontiers in pharmacology · 2025Article
- Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.Inflammatory bowel diseases · 2024Article
- Genetic ancestry in population pharmacogenomics unravels distinct geographical patterns related to drug toxicity.iScience · 2024Article
- APF2: an improved ensemble method for pharmacogenomic variant effect prediction.The pharmacogenomics journal · 2024Article
- Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Review
- Phenotype versus genotype to optimize cancer dosing in the clinical setting-focus on 5-fluorouracil and tyrosine kinase inhibitors.Pharmacology research & perspectives · 2024Review
- Clinical Implementation of Rare and NovelInternational journal of biological sciences · 2024Review
- The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity.Human genomics · 2023Article
- Challenges Related to the Use of Next-Generation Sequencing for the Optimization of Drug Therapy.Handbook of experimental pharmacology · 2023Article
- Population-Specific Distribution ofTherapeutics and clinical risk management · 2023Article
- A paradigm shift in pharmacogenomics: From candidate polymorphisms to comprehensive sequencing.Basic & clinical pharmacology & toxicology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundInter-individual differences in dihydropyrimidine dehydrogenase (DPYD encoding DPD) and thiopurine S-methyltransferase (TPMT) activity are important predictors for fluoropyrimidine and thiopurine toxicity. While several variants in these genes are known to decrease enzyme activities, many additional genetic variations with unclear functional consequences have been identified, complicating informed clinical decision-making in the respective carriers.
methodsWe used a novel pharmacogenetically trained ensemble classifier to analyse DPYD and TPMT genetic variability based on sequencing data from 138,842 individuals across eight populations.
resultsThe algorithm accurately predicted in vivo consequences of DPYD and TPMT variants (accuracy 91.4% compared to 95.3% in vitro). Further analysis showed high genetic complexity of DPD deficiency, advocating for sequencing-based DPYD profiling, whereas genotyping of four variants in TPMT was sufficient to explain >95% of phenotypic TPMT variability. Lastly, we provided population-scale profiles of ethnogeographic variability in DPD and TPMT phenotypes, and revealed striking interethnic differences in frequency and genetic constitution of DPD and TPMT deficiency.
conclusionThese results provide the most comprehensive data set of DPYD and TPMT variability published to date with important implications for population-adjusted genetic profiling strategies of fluoropyrimidine and thiopurine risk factors and precision public health.
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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.