Identification of Additional DPYD Polymorphisms That Increase the Risk of Severe Fluoropyrimidine Toxicity and Improve Predictive Accuracy when Combined with Previously Validated Variants
Abstract
PURPOSE: Fluoropyrimidine (FP) chemotherapy can cause life-threatening toxicity. Four DPYD polymorphisms (DPYD*2A, *13, p.Asp949Val, and HapB3) are most well established to increase FP toxicity risk. This study aimed to identify additional DPYD polymorphisms that increase FP severe toxicity. EXPERIMENTAL DESIGN: Adult patients treated with standard doses of systemic FP (5-fluorouracil/capecitabine) for any tumor type with available genetic data were included. The primary toxicity endpoint was a composite of Common Terminology Criteria for Adverse Event grade ≥3 toxicity or treatment modification due to toxicity in the first two FP cycles. A literature-curated list of suspected deleterious unvalidated DPYD variants was classified as uncommon (minor allele frequency
Fields of Study & Subjects
Colorectal Cancer Treatments and Studies
Cancer Treatment and Pharmacology
Biochemical and Molecular Research
Publication details
- Journal / source
- Clinical Cancer Research
- Publisher
- American Association for Cancer Research (AACR)
- Volume
- 32
- Issue
- 15
- Pages
- 3269–3276
- Publication date
- 27 February 2026
- Language
- EN