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Genetic Tests Identify Risk of Irinotecan-Induced Toxicity


Answers From the Lab

John Logan Black, M.D., explains how Mayo Clinic Laboratories' UGT1A1 tests (Mayo IDs: U1A1Q and UGTFZ) identify genetic variants that increase the risk of potentially life-threatening reactions to irinotecan, a chemotherapy agent.

Certain patients can experience severe and potentially life-threatening reactions to irinotecan, which is an antineoplastic agent approved for the treatment of multiple metastatic cancers. In this test-specific episode of the "Answers From the Lab" podcast, John Logan Black, M.D., explains how Mayo Clinic Laboratories' pharmacogenomicstests identify individuals at risk of these reactions to help determine safe dosage and personalize therapy.

The two tests target the UGT1A1 gene, which produces an enzyme that metabolizes bilirubin as well as irinotecan. "Poor metabolizers of irinotecan chemotherapies are at increased risk for life-threatening neutropenia. Physicians should consider a reduction in the dosing," Dr. Black says.

Mayo Clinic Laboratories' first UGT1A1 test(Mayo ID: U1A1Q) interrogates thymine-adenine repeats in the gene's promoter region. The second, a Sanger sequencing test (Mayo ID: UGTFZ), examines all five UGT1A1 exons in addition to the promoter.

"Most of the time, for a patient with a history of a normal bilirubin level before developing cancer, the UGT1A1 genotyping assay is enough," Dr. Black says. "But if your patient has a history of elevated bilirubin, then I would go to the Sanger sequencing, just to make sure you have a thorough assessment of this patient's gene before you give them irinotecan."

Listen to learn more about Mayo Clinic Laboratories' UGT1A1 testing.

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Barbara J. Toman

Barbara J. Toman is a Senior Communications Specialist at Mayo Clinic Laboratories. She is also the science writer for Mayo’s Neurosciences Update newsletter, which helps referring physicians to stay informed about Mayo’s treatment and research. Barbara has worked at Mayo Clinic since 2007. She enjoys international travel and cooking.