rs55886062

This is a missense variant in the DPYD gene.

Key Literature Trait Associations

Fluoropyrimidine Toxicity

DPYD*13 (I560S) causes complete loss of DPD enzyme function through a critical amino acid substitution. Although very rare, its clinical severity is equivalent to *2A — carriers are at high risk of fatal toxicity from 5-fluorouracil and capecitabine. CPIC and EMA include *13 in the recommended pre-treatment DPYD testing panel, and fluoropyrimidines are contraindicated in homozygous carriers.

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 C

OR —

p —

Candidate gene study

▶

ClinVar annotation

Drug Response★★★★

14 submitters36 publications

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

View on ClinVar →

▶

Research that mentions this SNP (2)

▶

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

DOI Metascience Observatory

▶

An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel

AssociationN=1,529Toshitaka Uchiyama et al.(2012)· Cancer Chemotherapy and Pharmacology

This pooled analysis of 6 randomized phase 3 trials (1529 patients with advanced NSCLC) demonstrates that chemotherapy-induced neutropenia (CIN) is a significant prognostic factor associated with longer overall survival, particularly severe CIN (HR 0.71, 95% CI: 0.53-0.95). The study does not analyze genetic polymorphisms but discusses the potential role of pharmacogenetic factors in predicting CIN risk, including SNPs in drug-metabolizing enzymes, transporters, and DNA repair genes.

Traits studied:Chemotherapy-induced neutropeniaOverall survival in advanced non-small-cell lung cancerTreatment efficacy in NSCLC

rs55886062

Key Literature Trait Associations

Fluoropyrimidine Toxicity

ClinVar annotation

Research that mentions this SNP (2)

Community Wiki

Comments