한국인 췌장암 환자에서 발견한 UGT1A1*37 대립유전자 1예 보고
Identification of a UGT1A1*37 Allele in a Korean Patient with Pancreatic Cancer
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초록
UGT1A1은 글루쿠로나이드화 반응을 촉진시키는 효소의 일종으로 빌리루빈 및 약물 대사에 관여한다. 특정 UGT1A1 유전자 다형성을 보유할 경우 UGT1A1 발현이 감소할 수 있는데, UGT1A1 유전자의 촉진자 부위에 위치한 TATA box에서 티민-아데닌 반복이 증가하는 UGT1A1*28 대립유전자가 대표적이다. 이리노테칸은 고형암의 항암치료에 사용되며 체내에서 SN-38으로 활성화되고 UGT1A1에 의해 글루쿠로나이드와 결합되어 제거된다. UGT1A1*28과 같이 UGT1A1의 활성도가 감소하는 경우 이리노테칸의 독성이 증가하여 중증 호중구감소증 및 설사와 같은 부작용이 발생할 수 있다. UGT1A1*37 대립유전자는 아시아인에서 보고된 바 없는 드문 대립유전자로서 UGT1A1*28 보다 UGT1A1 활성도가 더욱 감소되어 중증 호중구감소증과 연관되어 있음이 보고된 바 있다. 저자들은 췌장암으로 진단받은 69세 여성 환자에게서 UGT1A1*37 대립유전자를 아시아인에서 최초로 검출하였으며 치료 전 유전형 분석을 통하여 본 환자에서 이리노테칸에 대한 독성 반응의 발생 위험도가 증가할 것을 고려하여 이리노테칸을 배제하는 치료법으로 결정하였다.
Abstract
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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