Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy
Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy作者机构：Department of Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Geriatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Genetics and Complex Diseases Harvard T.H. Chan School of Public Health
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2016年第22卷第16期
页 面：4250-4258页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Supported by the National Natural Science Foundation of China No.81372664
主 题：Bilirubin Irinotecan Metastatic colorectal cancer Response UGT1A1*28
摘 要：AIM: To examine the predictive effects of baseline serum bilirubin levels and UDP-glucuronosyltransferase(UGT) 1A1*28 polymorphism on response of colorectal cancer to irinotecan-based ***: The present study was based on a prospective multicenter longitudinal trial of Chinese metastatic colorectal cancer(m CRC) patients treated with irinotecan-based chemotherapy(NCT01282658). Baseline serum bilirubin levels, including total bilirubin(TBil) and unconjugated bilirubin(UBil), were measured,and genotyping of UGT1A1*28 polymorphism was performed. Receiver operating characteristic curve(ROC) analysis was used to determine cutoff values of TBil and UBil. The TBil values were categorized into 13.0 or ≤ 13.0 groups; the UBil values were categorized into 4.1 or ≤ 4.1 groups. Combining the cutoff values of TBil and UBil, which was recorded as Co Bil, patients were classified into three groups. The classifier s performance of UGT1A1*28 and Co Bil for predicting treatment response was evaluated by ROC analysis. Associations between response and Co Bil or UGT1A1*28 polymorphism were estimated using simple and multiple logistic regression models. RESULTS: Among the 120 m CRC patients, the serum bilirubin level was significantly different between the UGT1A1*28 wild-type and mutant genotypes. Patients with the mutant genotype had an increased likelihood of a higher TBil(P = 0.018) and a higher UBil(P = 0.014) level compared with the wild-type genotype. Patients were stratified into three groups based on Co Bil. Group 1 was patients with TBil 13.0 and UBil 4.1; Group 2 was patients with TBil ≤ 13.0 and UBil 4.1; and Group 3 was patients with TBil ≤ 13.0 and UBil ≤ 4.1. Patients in Group 3 had more than a 10-fold higher likelihood of having a response in the simple(OR = 11.250; 95%CI: 2.286-55.367; P = 0.003) and multiple(OR = 16.001; 95%CI: 2.802-91.371; P = 0.002) analyses compared with the Group 1 individuals. Patients carrying the UGT1A1*28(TA)7 allele we
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