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題 名 | UDP-Glucuronosyltransferase 1A7 Polymorphisms Related to Tumor Response in Taiwanese Patients Treated with Irinotecan-Based Chemotherapy=在臺灣以抗癌妥為基礎的化療治療患者UDP-葡萄糖醛酸轉移1A7基因多態性與腫瘤反應的相關性 |
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作 者 | 林北江; 江支銘; 黃慶三; 洪欣園; 陳進勛; | 書刊名 | 中華民國大腸直腸外科醫學會雜誌 |
卷 期 | 23:3 2012.09[民101.09] |
頁 次 | 頁103-113 |
分類號 | 416.245 |
關鍵詞 | 大腸癌; 抗癌妥; 毒性; 多態性; Colorectal; Irinotecan; Toxicity; Polymorphisms; |
語 文 | 英文(English) |
中文摘要 | 背景 尿核甘雙磷酸葡萄糖醛酸基轉移酵素(uridine diphosphate-glucuronosyltransferase, UGT)具有基因多型性,已有許多研究報告指出,UGT1A基因的差異性與化療引起的毒性有關聯,而UGT1A基因在不同種族間有極大的差異。我們的目的在於研究台灣地區大腸直腸癌病人中,UGT1A1/UGT1A7/UGT1A9基因的多型性是否會影響以Irinotecan為主的化學治療之毒性和臨床療效。對象與方法 總共有115位罹患轉移性大腸直腸癌並接受以Irinotecan為主之化學治療的病人進入本臨床試驗,從這些病患的周邊血液萃取其基因組去氧核糖核酸(genomic DNA)並以聚合酵素連鎖反應為基礎的方式(PCR-based)作基因型的分析。我們藉此分析UGT1A基因型與化療毒性以及臨床治療結果之間的關連。結果 115位病人中只有一位(0.9%)具有UGT1A1*28基因。我們發現低活性的UGT1A1*28 基因和嗜中性白血球低下的發生率增加有顯著的相關性(Odd ratio 2.42, p =0.049)。結果也顯示基因型UGT1A1*6 [211G>A]與嗜中性白血球低下的發生有相關趨勢(odds ratio 2.18, p =0.084)且UGT1A7[622T>C]也有相同趨勢(odds ratio 2.05, p =0.087)。根據基因型,具有同質性UGT1A7[387G/G]的病患有較低的腫瘤反應(31.2% v 61.8%, OR =0.28, p=0.049)。在UGT1A haplotype II的病患也有較低的腫瘤反應,呈現邊際的顯著相關性(31.3% v 66.7%, OR=0.23, p=0.053)。結論 在接受FOLFIRI化學治療之轉移性大腸直腸癌的病患,UGT1A的基因多型性可作為預測嗜中性白血球低下的發生率和腫瘤對化療的反應性的顯著指標。 |
英文摘要 | Background. Many studies have reported an association between genetic variants of the UGT1A gene (uridine diphosphate-glucuronosyltransferase, UGT) and the development of toxicities. Considerable ethnic differences in genetic variations of the UGT1A locus have also been observed. The aim of this study was to comprehensively investigate genetic variation in UGT1A1/UGT1A7/UGT1A9, in order to evaluate the clinical influences of toxicities and subsequent outcome in Taiwanese patients undergoing irinotecan-based chemotherapy.Patients and Methods. One hundred and fifteen patients with metastatic colorectal cancer treated with irinotecan based chemotherapy were recruited. Genomic DNA was extracted from peripheral blood and genotyped using PCR-based methods. We analyzed the association between UGT1A genotypes and development of toxicities and response to chemotherapy. Results. Only one of the 115 patients (0.9%) was homozygous for UGT1A1*28 in this study. We observed a significant correlation between the low activity UGT1A1*28 genotypes and increasing incidence of neutropenia (odds ratio 2.42, p=0.049). There was also a trend of association between UGT1A1*6 [211G>A] genotype and the incidence of neutropenia (odds ratio 2.18, p=0.084) and between association between UGT1A7 [622T>C] genotype and the incidence of neutropenia (odds ratio 2.05, p=0.087). By genotype, patients with homozygous UGT1A7 [387G/G] showed a significantly lower response rate (31.2% vs. 61.8%, OR=0.28, p=0.049). Patients with UGT1A haplotype II also showed marginally significantly lower response rates (31.3% vs. 66.7%, OR=0.23, p=0.053). Conclusion. Genotyping of UGT1As polymorphisms provides significant predictors for neutropenia occurrence and tumour responses in metastatic CRC patients receiving a FOLFIRI regimen. |
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