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?

• UGT1A1*28 allele: ~0.26–0.31 in Caucasians; ~0.42–0.56 in African Americans; ~0.09–0.16 in Asians. 
• 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.

References