Trial reportJournal of the National Cancer Institute2014
DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer treatment (NCCTG N0147).
Trial report in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 3 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- Pooled it
- DPYD genetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: a systematic review.British journal of cancer · 2024Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update.Clinical pharmacology and therapeutics · 2018Guideline
- A thymine-challenge test to prospectively evaluate dihydropyrimidine dehydrogenase activity for risk of severe 5-fluorouracil-induced gastrointestinal toxicity.Cancer chemotherapy and pharmacology · 2025Trial
- Clinical Benefits and Utility of Pretherapeutic DPYD and UGT1A1 Testing in Gastrointestinal Cancer: A Secondary Analysis of the PREPARE Randomized Clinical Trial.JAMA network open · 2024Trial
- A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy.BMC medical genomics · 2023Trial
- Pharmacogenetic Analysis of the UK MRC (Medical Research Council) MAGIC Trial: Association of Polymorphisms with Toxicity and Survival in Patients Treated with Perioperative Epirubicin, Cisplatin, and 5-fluorouracil (ECF) Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients.British journal of cancer · 2017Trial
- Association between DPYD c.1129-5923 C>G/hapB3 and severe toxicity to 5-fluorouracil-based chemotherapy in stage III colon cancer patients: NCCTG N0147 (Alliance).Pharmacogenetics and genomics · 2016Trial
- Dihydropyrimidine Dehydrogenase Genotype-Phenotype Correlations in Plasma and Peripheral Blood Mononuclear Cells.Clinical pharmacology and therapeutics · 2026Article
- Trial of Preemptive Pharmacogenetic Testing in Underserved Patients (TOPP UP): Study Framework and Baseline Characteristics of Randomized Controlled Trial Participants.Clinical and translational science · 2026Article
- Uptake of DPYD and UGT1A1 testing in Italy and adherence to pharmacogenetic guidelines: A 5-year perspective from an EQA provider.British journal of clinical pharmacology · 2026Article
- Implementation and feasibility of DPYD-guided fluoropyrimidine use in a gastrointestinal oncology clinic at an academic medical center.Frontiers in oncology · 2026Article
- Global Investigation of Clinical Implementation Strategies for DPYD Testing to Guide Fluoropyrimidine Therapy.Clinical and translational science · 2026Article
- 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 Guide for Implementing DPYD Genotyping for Systemic Fluoropyrimidines into Clinical Practice.Clinical pharmacology and therapeutics · 2025Review
- Balance of care activity after EMA recommendation forFrontiers in pharmacology · 2025Article
- Influence of DPYD gene polymorphisms on 5-Fluorouracil toxicities in Thai colorectal cancer patients.Cancer chemotherapy and pharmacology · 2024Article
- Pharmacogenetic DPYD allele variant frequencies: A comprehensive analysis across an ancestrally diverse Iranian population.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- Lethal 5-Fluorouracil Toxicity in a Carrier ofJCO precision oncology · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundPrevious studies have suggested the potential importance of three DPYD variants (DPYD*2A, D949V, and I560S) with increased 5-FU toxicity. Their individual associations, however, in 5-FU-based combination therapies, remain controversial and require further systematic study in a large patient population receiving comparable treatment regimens with uniform clinical data.
methodsWe genotyped 2886 stage III colon cancer patients treated adjuvantly in a randomized phase III trial with FOLFOX or FOLFIRI, alone or combined with cetuximab, and tested the individual associations between functionally deleterious DPYD variants and toxicity. Logistic regressions were used to assess univariate and multivariable associations. All statistical tests were two-sided.
resultsIn 2594 patients with complete adverse event (AE) data, the incidence of grade 3 or greater 5FU-AEs in DPYD*2A, I560S, and D949V carriers were 22/25 (88.0%), 2/4 (50.0%), and 22/27 (81.5%), respectively. Statistically significant associations were identified between grade 3 or greater 5FU-AEs and both DPYD*2A (odds ratio [OR] = 15.21, 95% confidence interval [CI] = 4.54 to 50.96, P < .001) and D949V (OR = 9.10, 95% CI = 3.43 to 24.10, P < .001) variants. Statistical significance remained after adjusting for multiple variables. The DPYD*2A variant statistically significantly associated with the specific AEs nausea/vomiting (P = .007) and neutropenia (P < .001), whereas D949V statistically significantly associated with dehydration (P = .02), diarrhea (P = .003), leukopenia (P = .002), neutropenia (P < .001), and thrombocytopenia (P < .001). Although two patients with I560S had grade≥3 5FU-AEs; a statistically significant association could not be demonstrated because of its low frequency (P = .48).
conclusionIn the largest study to date, statistically significant associations were found between DPYD variants (DPYD*2A and D949V) and increased incidence of grade 3 or greater 5FU-AEs in patients treated with adjuvant 5-FU-based combination chemotherapy.
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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 OpenQuestion graph.