ArticleThe pharmacogenomics journal2019
DPYD*6 plays an important role in fluoropyrimidine toxicity in addition to DPYD*2A and c.2846A>T: a comprehensive analysis in 1254 patients.
Article in The pharmacogenomics journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Genetic Variants Associated with Fluoropyrimidine-Induced Toxicity in Real-World Patients After Pre-EmptivePharmaceuticals (Basel, Switzerland) · 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
- Navigating Cardiotoxicity in Cancer Treatment: Insights into Fluoropyrimidine-induced Cardiac Events.Current cardiology reviews · 2026Review
- Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution.World journal of gastrointestinal oncology · 2025Article
- Clinical impact of DPYD genotyping and dose adjustment in candidates for fluoropyrimidine treatment.Heliyon · 2024Article
- Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients.Current issues in molecular biology · 2024Article
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- Clinical Implementation of Rare and NovelInternational journal of biological sciences · 2024Review
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- Can immunotherapy reinforce chemotherapy efficacy? a new perspective on colorectal cancer treatment.Frontiers in immunology · 2023Review
- Implementing pharmacogenetic testing in fluoropyrimidine-treated cancer patients: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
- Role of Genetic Polymorphisms in Drug-Metabolizing Enzyme-Mediated Toxicity and Pharmacokinetic Resistance to Anti-Cancer Agents: A Review on the Pharmacogenomics Aspect.Clinical pharmacokinetics · 2022Review
- Metronomic chemotherapy in patients with advanced neuroendocrine tumors: A single-center retrospective analysis.Journal of neuroendocrinology · 2022Article
- Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data.Nature communications · 2022Article
- Pharmacogenetic Study of the Dihydropyridine Dehydrogenase Gene in Jordanian Patients with Colorectal Cancer.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Grading Central Diabetes Insipidus Induced by Immune Checkpoint Inhibitors: A Challenging Task.Frontiers in endocrinology · 2022Review
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Corrections and comments
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Authors and funding
26 authors at 13 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dihydropyrimidine dehydrogenase (DPYD) is a highly polymorphic gene and classic deficient variants (i.e., c.1236G>A/HapB3, c.1679T>G, c.1905+1G>A and c.2846A>T) are characterized by impaired enzyme activity and risk of severe adverse drug reactions (ADRs) in patients treated with fluoropyrimidines. The identification of poor metabolizers by pre-emptive DPYD screening may reduce the rate of ADRs but many patients with wild-type genotype for classic variants may still display ADRs. Therefore, the search for additional DPYD polymorphisms associated with ADRs may improve the safety of treatment with fluoropyrimidines. This study included 1254 patients treated with fluoropyrimidine-containing regimens and divided into cohort 1, which included 982 subjects suffering from gastrointestinal G≥2 and/or hematological G≥3 ADRs, and cohort 2 (control group), which comprised 272 subjects not requiring dose reduction, delay or discontinuation of treatment. Both groups were screened for DPYD variants c.496A>G, c.1236G>A/HapB3, c.1601G>A (DPYD*4), c.1627A>G (DPYD*5), c.1679T>G (DPYD*13), c.1896T>C, c.1905 + 1G>A (DPYD*2A), c.2194G>A (DPYD*6), and c.2846A>T to assess their association with toxicity. Genetic analysis in the two cohorts were done by Real-Time PCR of DNA extracted from 3 ml of whole blood. DPYD c.496A>G, c.1601G>A, c.1627A>G, c.1896T>C, and c.2194G>A variants were found in both cohort 1 and 2, while c.1905+1G>A and c.2846A>T were present only in cohort 1. DPYD c.1679T>G and c.1236G>A/HapB3 were not found. Univariate analysis allowed the selection of c.1905+1G>A, c.2194G>A and c.2846A>T alleles as significantly associated with gastrointestinal and hematological ADRs (p < 0.05), while the c.496A>G variant showed a positive trend of association with neutropenia (p = 0.06). In conclusion, c.2194G>A is associated with clinically-relevant ADRs in addition to the already known c.1905+1G>A and c.2846A>T variants and should be evaluated pre-emptively to reduce the risk of fluoropyrimidine-associated ADRs.
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