UGT1A1 Pharmacogenomic Testing
Why Genotyping Changes Outcomes
Understanding the genetic link to Irinotecan toxicity.
Mechanism of Toxicity
Irinotecan’s active metabolite (SN-38) is inactivated by UGT1A1. Reduced-function alleles (*28, *6) slow this process, increasing SN-38 exposure and the risk of severe side effects.
Who’s at Risk?
About 10% of North Americans are *28/*28 homozygotes. The *6 allele is common in East Asians (15-30%), predicting higher toxicity risk in these groups.
How Common Are the Risk Alleles?
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- UGT1A1*28 allele: ~0.26–0.31 in Caucasians; ~0.42–0.56 in African Americans; ~0.09–0.16 in Asians.
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- UGT1A1*6 allele: ~0.15–0.30 in Chinese, Korean, and Japanese populations.
Who Should Be Tested?
Identifying ideal candidates for pharmacogenomic testing.
Patients starting irinotecan at ≥180 mg/m² or as single-agent
Highest genotype–toxicity signal; informs initial dosing
Individuals with prior unexplained neutropenia/diarrhea on irinotecan
Possible UGT1A1 poor/intermediate metabolizer
East Asian ancestry (common *6) or known *28 family history
Elevated prevalence of reduced-function alleles
Fragile patients (elderly, comorbid, polypharmacy)
Preventable toxicity may derail treatment plan
Your Journey with Genolife Services
A clear path to optimizing Irinotecan therapy.
Pre-test Counselling
Discuss benefits, limits, and alternative irinotecan dosing strategies.
Sample Collection
A simple blood sample is all that’s needed (no fasting required).
Expert Interpretation
Results are reviewed by a team including a Clinical Geneticist, Pharmacist, and Oncologist.
Post test
Offered for relatives who may also need irinotecan or have a history of related toxicity.
Ready to plan for a safer health future?
Contact us for a consultation with our Genetic Counselor/Pharmacogenomics Specialist about the Irinotecan Toxicity Risk Panel or other genetic tests.
References
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- NCBI Medical Genetics Summaries. Irinotecan Therapy and UGT1A1 Genotype. Updated overview of mechanism, allele frequencies, FDA labeling, and dose-toxicity relationships.
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- PharmGKB. Irinotecan + UGT1A1 clinical and variant annotations; allele frequency resources.
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- CPIC. UGT1A1–Irinotecan evidence status update (workstream). Confirms active evaluation of dosing guidance within CPIC
