한국인 췌장암 환자에서 발견한 UGT1A1*37 대립유전자 1예 보고

초록

UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme that catalyzes glucuronidation of substances, including bilirubin and other drug metabolites. Certain UGT1A1 polymorphisms reduce UGT1A1 activity, notably UGT1A1*28 contains thymine-adenine repeats in the TATA box of the promotor region. Irinotecan, a chemotherapy agent for solid cancers, is converted in the body to an active metabolite, SN-28, and then excreted, after being conjugated with glucuronide by UGT1A1. If UGT1A1 activity decreases (e.g. UGT1A1*28), the risk of irinotecan toxicity increases, which can develop into severe neutropenia and diarrhea. UGT1A1*37, a rare allele that has never been found in Asians, was previously reported to be associated with severe neutropenia by reducing UGT1A1 activity further than UGT1A1*28. In this study, we first detected UGT1A1*37 in a 69-year-old Korean woman diagnosed with pancreatic cancer and excluded irinotecan from her chemotherapy regimen, in consideration of the increased risk of toxicity, based on pre-treatment UGT1A1 genotyping.

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