UDP-Glucuronosyltransferase 1A7 Polymorphisms Related to Tumor Response in Taiwanese Patients Treated with Irinotecan-Based Chemotherapy

在台灣以抗癌妥為基礎的化療治療患者UDP-葡萄糖醛酸轉移酶1A7基因多態性與腫瘤反應的相關性

林北江(Pei-Chiang Lin) ； 江支銘(Jy-Ming Chiang) ； 黃慶三(Ching-Shan Huang) ； 洪欣園(Hsin-Yuan Hung) ； 陳進勛(Jinn-Shiun Chen)

《中華民國大腸直腸外科醫學會雜誌》 23卷3期 (2012/09) Pp. 103-113

https://doi.org/10.6312/SCRSTW.2012.23(3).10026

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.

關鍵字

大腸癌 ； 抗癌妥 ； 毒性 ； 多態性

並列摘要

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.

並列關鍵字

Colorectal ； Irinotecan ； Toxicity ； Polymorphisms