<i>DPYD</i>Genotyping to Predict Adverse Events Following Treatment With Fluorouracil-Based Adjuvant Chemotherapy in Patients With Stage III Colon Cancer

Boige, Valérie; Vincent, Marc; Alexandre, Philippe; Tejpar, Sabine; Landolfi, Stefania; Malicot, Karine Le; Greil, Richard; Cuyle, P J; Yilmaz, Mette Karen; Faroux, Roger; Matzdorff, Axel; Salazar, Ramón; Lepage, Côme; Taı̈eb, Julien; Laurent‐Puig, Pierre

doi:10.1001/jamaoncol.2015.5392

Cited by 64 publications

(65 citation statements)

References 27 publications

(21 reference statements)

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“…The objective of our case-control study was to analyse the two other variants, c.2846A>T and c.1679T>G, in subjects who have presented FAEs not DPYD*2A correlated, in order to confirm their clinical relevance and to evaluate their possible improvement of predicting toxicity when introduced in the pre-treatment screening. Furthermore, in consideration of the results of some recent studies, 5,[23][24][25] we evaluated the potential clinical impact of the c.2194G>A SNP, a more frequent variant of DPYD with an interesting correlation with fluoropyrimidine-related toxicity.…”

Section: Introductionmentioning

confidence: 99%

The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study

et al. 2019

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Background Deleterious polymorphisms in the gene encoding DPD (DPYD) may result in severe reduction of DPD enzymatic activity that causes life-threatening toxicities when the standard dose of fluorouracil is used. The best panel of single-nucleotide polymorphism (SNPs) of DPYD is not well defined. Methods In 2011, we began screening DPYD*2A in patients candidate for fluoropyrimidine-based chemotherapy. We planned a case-control study with all cases of DPYD*2A wild type who developed toxicity ≥G3 and with a cohort of patients who did not present severe toxicities. Then, we tested the additional SNPs: c.2846A>T, c.1679T>G, c.2194G>A. Results From 2011 to 2016, we screened 1827 patients for DPD deficiency; of those, 31 subjects (1.7%) showed DPYD*2A SNP. We selected 146 subjects who developed severe toxicities (Cases) and 220 patients who experienced no or mild toxicities (Controls); 53 patients carried one of the additional SNPs: 35 subjects (66%) fell into the Cases and 18 (34%) into the Controls ( p < 0.0001). c.2194G>A was the most frequent SNP (12.5%) and showed a correlation with neutropenia. We confirmed that c.2846A>T and c.1679T>G were related to various toxicities. Conclusions The additional DPYD polymorphisms could enhance the prevention of fluoropyrimidine toxicity. c.2194G>A is the most frequent polymorphism and it was found to be associated with neutropenia.

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Section: Introductionmentioning

confidence: 99%

The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study

et al. 2019

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“…That study also confirmed the significant predictive value of rs67376798 (D949V), but not for DPYD *2A and DPYD *13, which are the other variants included in the Clinical Pharmacogenetics Implementation Consortium Guidelines. This apparently surprising discrepancy may simply be due to the low allelic variant frequency in the population studied by Boige et al [4]. Consequently, a strategy considering more frequent DPYD variants may be relevant to understand the cause-effect correlation between toxicity and heritability, which is currently lacking in the assessment of only rare variants.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Boige et al [4] made important advances in this direction by investigating 25 DPYD variants in a large cohort of patients with stage III colon cancer treated with FOLFOX4 adjuvant chemotherapy. Among the 12 DPYD variants found to be polymorphic, statistically significant associations with grade 3 or greater fluorouracil adverse events were observed for carriers of rs67376798 (D949V: OR 6.3; 95% CI 2.0-27.0) and rs1801160 (V732I: OR 1.7; 95% CI 1.3-2.4) [4].…”

Section: Introductionmentioning

confidence: 99%

“…Among the 12 DPYD variants found to be polymorphic, statistically significant associations with grade 3 or greater fluorouracil adverse events were observed for carriers of rs67376798 (D949V: OR 6.3; 95% CI 2.0-27.0) and rs1801160 (V732I: OR 1.7; 95% CI 1.3-2.4) [4]. That study also confirmed the significant predictive value of rs67376798 (D949V), but not for DPYD *2A and DPYD *13, which are the other variants included in the Clinical Pharmacogenetics Implementation Consortium Guidelines.…”

Section: Introductionmentioning

confidence: 99%

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Fluoropyrimidine-Associated Toxicity in Two Gastrointestinal Cancer Patients: Potential Role of Common DPYD Polymorphisms

Falvella

Luoni²,

Cheli³

et al. 2017

Chemotherapy

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While the majority of patients can be treated safely with fluoropyrimidine, some experience severe fluoropyrimidine-associated toxicity. The frequency and severity of these adverse events vary from patient to patient and are partially explained by genetic polymorphism into the dihydropyrimidine dehydrogenase (DPYD) gene. Carriers of the rare allelic variants DPYD*2A, DPYD*13, and DPYD D949V are more likely to experience severe adverse reactions during fluoropyrimidine-based therapy. However, these 3 genetic variants explain only a small percentage of the overall drug toxicity, and more frequent ones such as homozygous or compound heterozygous DPYD V732I can play a key role.

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“…Therefore, genetic variants of DNA repair genes in the form of SNPs could modulate treatment response. A recent large pharmacogenetic analysis examining 66 SNPs showed that there is an association between SNPs in DNA repair genes and response to neoadjuvant CRT in patients with locally advanced rectal cancer (12) (10).…”

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confidence: 99%

Focusing the management of rectal cancer

2016

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DPYDGenotyping to Predict Adverse Events Following Treatment With Fluorouracil-Based Adjuvant Chemotherapy in Patients With Stage III Colon Cancer

Abstract: eudract Identifier 2005-003463-23.

Cited by 64 publications

References 27 publications

The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study

The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study

Fluoropyrimidine-Associated Toxicity in Two Gastrointestinal Cancer Patients: Potential Role of Common DPYD Polymorphisms

Focusing the management of rectal cancer

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