UGT1A1*28 Polymorphisms in Metastatic Colorectal Cancer: A Retrospective Study

檢測UGT1A1*28基因多型性治療轉移性大腸直腸癌之臨床經驗

陳苓萍(Ling-Ping Chen) ； 施盈逸(Ying-Yih Shih) ； 張園鑫(Yuan-Hsin Chang) ； 劉惠文(Hui-Wen Liu) ； 宋詠娟(Yung-Chuan Sung)

《輔仁醫學期刊》 15卷3期 (2017/09) Pp. 131-140

https://doi.org/10.3966/181020932017091503002

摘要

Purpose: Polymorphism of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene is known to be associated with an increased risk of irinotecan-induced toxicities in patients with metastatic colorectal carcinoma. However, limited data are available regarding the UGT1A1*28 genotype in Taiwanese patients with metastatic colorectal cancer. Methods: Between January 2011 and June 2013, metastatic colorectal cancer patients receiving first-line irinotecan-based chemotherapy at Cathay General Hospital and Sijhih Cathay General Hospital who underwent UGT1A1*28 genotyping were enrolled in the present study. Patient characteristics, treatments, adverse events, and outcomes were retrospectively analyzed. Results: In all, 104 patients were analyzed, including 81 (77.9%) with the homozygous wild type TA6/6, 21 (20.2%) with the heterozygous mutant type TA6/7, and 2 (1.9%) with the homozygous mutant type TA7/7. No significant difference in the irinotecan dose intensity was observed among genotypes (p = 0.395). Furthermore, no significant differences in tumor response (p = 0.450) or survival outcomes were observed (progression-free survival, p = 0.713; overall survival, p = 0.854). Neutropenia (p = 0.433) and diarrhea (p = 0.896) had a similar incidence among genotypes. Leukopenia (p = 0.015) was the only side effect that differed among subgroups. Conclusions: UGT1A1*28 genotype TA7/7 is uncommon in Taiwanese patients with metastatic colorectal cancer. A marginal statistical difference in irinotecan-related side effects was observed among genotypes. This finding may have been confounded by physicians adjusting the dosage on the basis of genotype and clinical information. Larger-scale studies are warranted to verify this finding.

關鍵字

Colorectal cancer ； Polymorphism ； UGT1A1 ； Irinotecan

並列摘要

目的：許多文獻已經證實轉移性大腸直腸癌UGT1A1基因多型性影響化療藥物irinotecan（抗癌妥）的副作用嚴重程度。然而目前少有台灣轉移性大腸直腸癌常規檢驗UGT1A1基因多型性的報告，因而藉由此研究分享國泰醫院的治療經驗。方法：收錄2011年至2013年6月間，於國泰醫院及汐止國泰醫院診斷為轉移性大腸直腸癌，且病患接受第一線含有irinotecan的化療處方，同時抽血檢測UGT1A1基因多型性。本研究回溯性分析上述病患特徵、治療、副作用及成效。結果：共104人納入分析，其中81人（77.9%）為UGT1A1*28野生基因型TA6/6，另外21人（20.2%）為突變異合子型TA6/7，僅2人（1.9%）為突變同合子型TA7/7。在不同的UGT1A1*28基因型間，病人的化療藥物強度（p=0.395）、治療反應（p=0.450）、無疾病進展存活率（p=0.713）及整體存活率（p=0.854）並未出現統計學差異。副作用方面，除白血球低下達到顯著差異（p=0.015），其他副作用則在各基因型的發生率相仿，包含嗜中性白血球低下（p=0.433）及腹瀉（p=0.896）。結論：在台灣，UGT1A1*28突變同合子型TA7/7並非常見基因型，與irinotecan相關的副作用在不同基因型僅呈現些微差異，推測是因為臨床醫師會依據UGT1A1基因型及病患整體條件調整化療藥物劑量，進而影響臨床副作用發生頻率，未來還需更大規模的研究證實UGT1A1基因型的實際影響。

並列關鍵字

大腸直腸癌 ； 基因多型性 ； UGT1A1 ； irinotecan