DPYD Variants to Predict 5-FU Toxicity: The Ultimate Proof
Menée sur 2 594 patients atteints d'un cancer du côlon de stade III, cette étude met en évidence une association entre trois variants du gène DPYD et la toxicité du 5-fluorouracile dans le cadre d'une chimiothérapie adjuvante combinant plusieurs agents thérapeutiques
Based upon the evidence that pyrimidinemia was familial and caused by a genetic deficiency in the dihydropyrimidine dehydrogenase gene (DPYD ), the seminal discovery on the heritability of 5-fluorouracil (5-FU) toxicity opened the gate to the flood of studies on the genetic predisposition to severe toxicity in patients treated with fluoropyrimidines. In this issue of the Journal, Lee et al. report the results of a pharmacogenetic study in colorectal cancer patients treated with 5-FU–based therapy in the adjuvant setting. It provides the ultimate evidence for variation in the DPYD locus as a major determinant of patient safety. *2A and D949V are two DPYD variants with a strong effect size (odds ratios [ORs] of 15.21 and 9.10, respectively) for “5-FU-related” grade 3 or higher toxicities, with a strong association also for all grade 3 or higher toxicities. Hence, the occurrence of these heritable variants poses a considerable risk for patients and a challenge to patient management to preserve dose intensity.
Journal of the National Cancer Institute , éditorial en libre accès, 2014