Dihydropyrimidine dehydrogenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine?

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Personalized Medicine and Imaging Polymorphisms in MIR27A Associated with Early-Onset Toxicity in Fluoropyrimidine-Based Chemotherapy

Purpose: ThemicroRNAmiR-27awas recently shown to directly regulate dihydropyrimidine dehydrogenase (DPD), the key enzyme in fluoropyrimidine catabolism. A common polymorphism (rs895819A>G) in themiR-27a genomic region (MIR27A) was associated with reduced DPD activity in healthy volunteers, but the clinical relevance of this effect is still unknown. Here, we assessed the association of MIR27A ge...

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Correlation between dihydropyrimidine dehydrogenase and efficacy and toxicity of fluoropyrimidine drugs.

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Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.

The fluoropyrimidines are the mainstay chemotherapeutic agents for the treatment of many types of cancers. Detoxifying metabolism of fluoropyrimidines requires dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene), and reduced or absent activity of this enzyme can result in severe, and sometimes fatal, toxicity. We summarize evidence from the published literature supporting this assoc...

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Strong Association of a Common Dihydropyrimidine Dehydrogenase Gene Polymorphism with Fluoropyrimidine-Related Toxicity in Cancer Patients

BACKGROUND Cancer patients carrying mutations in the dihydropyrimidine dehydrogenase gene (DPYD) have a high risk to experience severe drug-adverse effects following chemotherapy with fluoropyrimidine drugs such as 5-fluorouracil (5-FU) or capecitabine. The pretreatment detection of this impairment of pyrimidine catabolism could prevent serious, potentially lethal side effects. As known deleter...

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5-Fluorouracil toxicity and dihydropyrimidine dehydrogenase enzyme: implications for practice.

5-fluorouracil (5-FU) is a fluorinated pyrimidine analog, which is commonly used in combination chemotherapy for treating solid tumors. Dihydropyrimidine dehydrogenase plays an important role in catabolism and clearance of 5-FU. Any alteration in that sequence of enzymatic activity can lead to toxicity and even death in some patients. The most common loss of a functional allele of the dihydropy...

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ژورنال

عنوان ژورنال: EPMA Journal

سال: 2010

ISSN: 1878-5077,1878-5085

DOI: 10.1007/s13167-010-0041-2