Trial reportPloS one2013
Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pooled it
- A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.Clinical and translational science · 2024Pooled it
- Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis.British journal of cancer · 2024Pooled it
- 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
- Colorectal Cancer: Differential Gene Expression and In Vitro Response to 5-Fluorouracil, Novel Fluoropyrimidine F10, and Potential Synergy with Lupeol.International journal of molecular sciences · 2025Article
- Enzymatic carbon-fluorine bond cleavage by human gut microbes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Expansion of a bacterial operon during cancer treatment ameliorates fluoropyrimidine toxicity.Science translational medicine · 2025Observational
- Genetic variants and clinical determinants affecting the response to 5-Fluorouracil-based treatment in Chilean patients with advanced colorectal cancer.Frontiers in oncology · 2025Article
- Article
- Expansion of a bacterial operon during cancer treatment ameliorates drug toxicity.bioRxiv : the preprint server for biology · 2024Article
- Association of Single-Nucleotide Polymorphisms in Capecitabine Bioactivation Pathway with Adjuvant Therapy Safety in Colorectal Cancer Patients.Pharmaceutics · 2023Article
- Genetic Variants in the Mitochondrial Thymidylate Biosynthesis Pathway Increase Colorectal Cancer Risk.Current oncology (Toronto, Ont.) · 2023Article
- Article
- Pharmacogenomic-guided dosing of fluoropyrimidines beyondFrontiers in pharmacology · 2023Review
- Rs11479 inPharmacogenomics and personalized medicine · 2023Article
- Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism.Nature microbiology · 2022Article
- Colorectal cancer carcinogenesis: From bench to bedside.World journal of gastrointestinal oncology · 2022Review
- Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis.The oncologist · 2021Article
- Review
- The Road so Far in Colorectal Cancer Pharmacogenomics: Are We Closer to Individualised Treatment?Journal of personalized medicine · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers.
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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.