Impact of Routine UGT1A1 Genotyping Before Irinotecan Chemotherapy in Taiwanese Cancer Patients

Irinotecan is commonly used to treat lung, colorectal, pancreatic, stomach, esophageal, and other types of cancer. The main metabolic pathway of SN-38, the active product of Irinotecan, is grape glycoalkaloid acidification by UDP - glucuronosyltransferase (UGT1A1) and then excreted through bile and urine. Clinically, Irinotecan treatment can cause many adverse reactions, and differences in UGT1A1 genotypes can lead to structural changes or functional defects in enzymes, causing reduced acidification of grape glycolaldehyde, and increasing Irinotecan side effects. Therefore, if the patient's ability to metabolize the drug can be assessed before taking the drug, it will be of great help in treatment.

Until 2021, cancer will remain the top ten causes of death in Taiwan, of which colorectal and pancreatic cancer rank third and seventh among the top ten cancers in Taiwan, respectively, and these two cancers often use complex chemotherapy including irinotecan. Routine detection of UGT1A1 genotype in patients with colorectal and pancreatic cancer before irinotecan treatment predicts the drug metabolism capacity of irinotecan and adjusts the dose, allowing patients receiving irinotecan to reduce the harm of side effects. At present, the UGT1A1 genotype evaluated is usually only UGT1A1*28, but the common UGT1A1 genotype in Taiwan also has UGT1A1*6 and UG1A1*63, etc. There is no literature on Taiwanese cancer patients with actual irinotecan chemotherapy, so this study aims to explore the influence of the UGT1A1 genotype and develop other UGT1A1 genotype test methods. It is expected that molecular testing tools can improve cancer precision medicine and provide personalized medicine.