UGT1A1 Gene Guide for Cancer Medicines

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is an enzyme in our body that breaks down irinotecan, which is commonly used to treat certain gastrointestinal cancers. A person with partial UGT1A1 enzyme activity is called a UGT1A1 intermediate metabolizer. About 40 in 100 people are UGT1A1 intermediate metabolizers. A person with complete loss of UGT1A1 enzyme activity is called a UGT1A1 poor metabolizer. About 15 in 100 people are UGT1A1 poor metabolizers.

Your medical team can make changes to your treatment if UGT1A1 genetic testing shows you are at increased risk of experiencing severe side effects with irinotecan. Individuals who are UGT1A1 poor metabolizers cannot break down the active component of irinotecan which can result in a buildup of drug in the body.

Sometimes, serious side effects can happen early on during treatment in a person with UGT1A1 poor metabolism. Some of these serious side effects include low blood counts called neutropenia and diarrhea. In most instances, a reduction in irinotecan dose can help prevent severe toxicities for those who are UGT1A1 poor metabolizers.

The UGT1A1 gene provides instructions for making the UGT1A1 enzyme. UGT1A1 gene testing can find out if you have any variants, also called mutations, in the gene that affects your UGT1A1 enzyme activity. A blood sample will be collected and sent to the laboratory for testing. Results are usually available in one or two weeks.

Your medical team can use this information to make changes to your treatment regimen to reduce your risk of serious side effects. If you are a UGT1A1 intermediate metabolizer, your medical team may prescribe their planned dose of the medicine and monitor you closely for side effects. If you are a UGT1A1 poor metabolizer, your medical team may start a lower dose of the medicine and/or monitor you more closely for side effects. Notify your healthcare provider if genetic testing shows you have UGT1A1 deficiency, especially if you are getting care outside of Moffitt.

UGT1A1 is also involved in the metabolism of bilirubin, which comes from the normal breakdown of red blood cells. Genetic variants in UGT1A1 are associated with Gilbert’s syndrome, which may result in mild hyperbilirubinemia (buildup of bilirubin in the blood). Gilbert’s syndrome is typically observed in UGT1A1 poor metabolizers.

Your medical team may prescribe their planned dose of the medicine if testing shows that you have normal UGT1A1 enzyme activity. Keep in mind that even when no UGT1A1 gene mutation is found, some people may still develop side effects. Other factors, such as drug-drug interactions, can also play a role in how the body responds to medicines.