rs67376798

This is a missense variant in the DPYD gene.

Key Literature Trait Associations

Fluoropyrimidine Toxicity

DPYD D949V causes reduced (but not absent) dihydropyrimidine dehydrogenase activity. Heterozygous carriers are at increased risk of fluoropyrimidine toxicity but retain partial enzyme function. CPIC recommends a 50% dose reduction of 5-fluorouracil or capecitabine for heterozygous carriers, with subsequent dose titration based on clinical tolerance and toxicity monitoring.

Amstutz U et al. “Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update.” Clinical Pharmacology and Therapeutics 103(2):210-216 (2018)
Allele A
OR —
p —
Candidate gene study
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ClinVar annotation

Drug Response★★★★
15 submitters58 publications

not provided; Fluorouracil response; Dihydropyrimidine dehydrogenase deficiency; Inborn genetic diseases; fluorouracil response - Toxicity; fluorouracil response - Other; capecitabine response - Toxicity; tegafur response - Toxicity; DPYD-related disorder

View on ClinVar →
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Research that mentions this SNP (1)

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DPYDGenotyping to Predict Adverse Events Following Treatment With Fluorouracil-Based Adjuvant Chemotherapy in Patients With Stage III Colon Cancer
AssociationN=1,545Valérie Boige et al.(2016)· JAMA Oncology

This pharmacogenetic secondary analysis of 1,545 stage III colon cancer patients from the PETACC-8 trial identified two DPYD variants significantly associated with grade 3+ fluorouracil-related adverse events: D949V (rs67376798, OR 6.3, p<0.001) and V732I/DPYD*6 (rs1801160, OR 1.7, p<0.001). The V732I association was validated in an independent cohort of 339 metastatic colorectal cancer patients treated with FOLFOX regimens.

Traits studied:DiarrheaFluorouracil-related adverse eventsGastrointestinal adverse eventsGrade 3+ hematologic adverse eventsMucositisNeutropenia
DOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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