SynthesisBritish journal of cancer2024
Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis.
Synthesis in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Trial
- Metabolic Alterations in Blood and Saliva During the First Two Cycles of Adjuvant Chemotherapy Correlate with 5-FU Dose Reduction Requirement in Patients with Colorectal Cancer.European journal of drug metabolism and pharmacokinetics · 2026Article
- Allelic Variants of theGenes · 2026Observational
- Evolution or Revolution in Colorectal Cancer Treatment: Present and Future of New Therapeutic Options. A Narrative Review.Oncology research · 2026Review
- Identification of a largeFrontiers in pharmacology · 2026Article
- Association of DPYD rs4294451, plasma uracil concentration, and sex with 5-fluorouracil exposure in patients with gastrointestinal cancer.Cancer chemotherapy and pharmacology · 2025Article
- Real-world study on fluoropyrimidine-related toxicity outcomes in cancer patients with select DPYD variant alleles that received DPYD genotype-guided dosing.International journal of cancer · 2025Article
- A Lack of Complete Linkage Disequilibrium Between c.1236G>A and c.1129-5923C>G HapB3 Variants ofInternational journal of molecular sciences · 2025Article
- Unrecognized mutations in DPYD* 2 A wild-type rectal cancer patients receiving postoperative 5-FU-based chemotherapy - do they have a clinical impact?Cancer chemotherapy and pharmacology · 2025Article
- DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.Cancer chemotherapy and pharmacology · 2025Article
- Article
- Article
- Clinical implications of a gain-of-function genetic polymorphism in DPYD (rs4294451) in colorectal cancer patients treated with fluoropyrimidines.Frontiers in pharmacology · 2024Article
- Clinical Implementation of Rare and NovelInternational journal of biological sciences · 2024Review
Corrections and comments
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Authors and funding
30 authors at 20 institutions in 10 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDihydropyrimidine dehydrogenase (DPD) deficiency is the main known cause of life-threatening fluoropyrimidine (FP)-induced toxicities. We conducted a meta-analysis on individual patient data to assess the contribution of deleterious DPYD variants *2A/D949V/*13/HapB3 (recommended by EMA) and clinical factors, for predicting G4-5 toxicity.
methodsStudy eligibility criteria included recruitment of Caucasian patients without DPD-based FP-dose adjustment. Main endpoint was 12-week haematological or digestive G4-5 toxicity. The value of DPYD variants *2A/p.D949V/*13 merged, HapB3, and MIR27A rs895819 was evaluated using multivariable logistic models (AUC).
resultsAmong 25 eligible studies, complete clinical variables and primary endpoint were available in 15 studies (8733 patients). Twelve-week G4-5 toxicity prevalence was 7.3% (641 events). The clinical model included age, sex, body mass index, schedule of FP-administration, concomitant anticancer drugs. Adding *2A/p.D949V/*13 variants (at least one allele, prevalence 2.2%, OR 9.5 [95%CI 6.7-13.5]) significantly improved the model (p < 0.0001). The addition of HapB3 (prevalence 4.0%, 98.6% heterozygous), in spite of significant association with toxicity (OR 1.8 [95%CI 1.2-2.7]), did not improve the model. MIR27A rs895819 was not associated with toxicity, irrespective of DPYD variants.
conclusionsFUSAFE meta-analysis highlights the major relevance of DPYD *2A/p.D949V/*13 combined with clinical variables to identify patients at risk of very severe FP-related toxicity.
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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 Socratic graph.