目的系统评价尿苷二磷酸葡萄糖醛酸转移酶1A1*6(uridine diphosphate glucuronide transferase 1A1*6,UGT1A1*6)基因多态性与伊立替康(Irinotecan,IRI)治疗国人结直肠癌的疗效及不良反应的相关性。方法检索PubMed、Embase、The Cochrane...目的系统评价尿苷二磷酸葡萄糖醛酸转移酶1A1*6(uridine diphosphate glucuronide transferase 1A1*6,UGT1A1*6)基因多态性与伊立替康(Irinotecan,IRI)治疗国人结直肠癌的疗效及不良反应的相关性。方法检索PubMed、Embase、The Cochrane Library(2020年2期)、中国生物医学文献数据库、中国知网、万方、维普中文科技期刊数据库中评价UGT1A1*6基因多态性与以IRI为基础化疗方案治疗结直肠癌疗效及不良反应的相关文献,检索时限均为建库至2020年2月。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险,使用NOS量表(Newcastle-Ottawa Scale)评价文献研究质量。采用Stata 12.0软件进行Meta分析,计算OR及95%CI。结果本研究共纳入28项病例对照研究,共有2926例患者纳入研究。结果表明,在5种基因模型中,UGT1A1*6多态性与临床疗效之间差异无统计学意义(P>0.05),但与粒细胞减少有相关性(G vs A:OR=0.61,95%CI:0.51~0.73,P=0.00;GG vs AA:OR=0.34,95%CI:0.22~0.53,P=0.00;GA vs AA:OR=0.55,95%CI:0.34~0.88,P=0.01;GG+GA vs AA:OR=0.39,95%CI:0.25~0.61,P=0.00;GG vs AA+GA:OR=0.41,95%CI:0.30~0.56,P=0.00);而仅杂合型(GA vs AA)与腹泻的发生率无相关性(P>0.05),其余均与腹泻的发生率有相关性(G vs A:OR=0.41,95%CI:0.32~0.53,P=0.00;GG vs AA:OR=0.37,95%CI:0.21~0.63,P=0.00;GG+GA vs AA:OR=0.43,95%CI:0.25~0.74,P=0.00;GG vs AA+GA:OR=0.32,95%CI:0.22~0.47,P=0.00);在隐形模型中,与严重白细胞减少的发生有相关性(GG vs AA+GA:OR=0.08,95%CI:0.04~0.14,P=0.00),而与血红蛋白及血小板减少均无相关性(P>0.05)。结论UGT1A1*6基因多态性是一个能够预测伊立替康化疗后所导致的毒性作用,尤其是中性粒细胞减少和腹泻发生风险的分子标志物,在白细胞减少发生风险方面也有一定的意义。展开更多
Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of i...Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.展开更多
伊立替康(irinotecan)不良反应与UGT1A1*6单核苷酸多态性相关,目前应用的单核苷酸多态性检测方法具有耗时长、开盖易污染、操作繁琐等缺点,因此需建立一种操作简便且不易污染的适合临床应用的新方法。本研究利用3种已知基因型的DNA样本...伊立替康(irinotecan)不良反应与UGT1A1*6单核苷酸多态性相关,目前应用的单核苷酸多态性检测方法具有耗时长、开盖易污染、操作繁琐等缺点,因此需建立一种操作简便且不易污染的适合临床应用的新方法。本研究利用3种已知基因型的DNA样本建立基于级联核酸侵入反应的real-time PCR法检测UGT1A1*6多态性的最佳反应体系,并对其检测口腔咽拭子样本的灵敏度和准确性进行了考察。结果显示,本文成功建立了基于级联核酸侵入反应的UGT1A1*6基因多态性检测方法,可用于咽拭子样本的分型检测,其灵敏度达到6 ng DNA,分型准确性达到100%。因其取样方便对人体无创,单管闭管检测不易产生交叉污染,具有用于临床检测伊立替康的个体化用药相关UGT1A1*6基因多态性的潜力。展开更多
文摘目的系统评价尿苷二磷酸葡萄糖醛酸转移酶1A1*6(uridine diphosphate glucuronide transferase 1A1*6,UGT1A1*6)基因多态性与伊立替康(Irinotecan,IRI)治疗国人结直肠癌的疗效及不良反应的相关性。方法检索PubMed、Embase、The Cochrane Library(2020年2期)、中国生物医学文献数据库、中国知网、万方、维普中文科技期刊数据库中评价UGT1A1*6基因多态性与以IRI为基础化疗方案治疗结直肠癌疗效及不良反应的相关文献,检索时限均为建库至2020年2月。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险,使用NOS量表(Newcastle-Ottawa Scale)评价文献研究质量。采用Stata 12.0软件进行Meta分析,计算OR及95%CI。结果本研究共纳入28项病例对照研究,共有2926例患者纳入研究。结果表明,在5种基因模型中,UGT1A1*6多态性与临床疗效之间差异无统计学意义(P>0.05),但与粒细胞减少有相关性(G vs A:OR=0.61,95%CI:0.51~0.73,P=0.00;GG vs AA:OR=0.34,95%CI:0.22~0.53,P=0.00;GA vs AA:OR=0.55,95%CI:0.34~0.88,P=0.01;GG+GA vs AA:OR=0.39,95%CI:0.25~0.61,P=0.00;GG vs AA+GA:OR=0.41,95%CI:0.30~0.56,P=0.00);而仅杂合型(GA vs AA)与腹泻的发生率无相关性(P>0.05),其余均与腹泻的发生率有相关性(G vs A:OR=0.41,95%CI:0.32~0.53,P=0.00;GG vs AA:OR=0.37,95%CI:0.21~0.63,P=0.00;GG+GA vs AA:OR=0.43,95%CI:0.25~0.74,P=0.00;GG vs AA+GA:OR=0.32,95%CI:0.22~0.47,P=0.00);在隐形模型中,与严重白细胞减少的发生有相关性(GG vs AA+GA:OR=0.08,95%CI:0.04~0.14,P=0.00),而与血红蛋白及血小板减少均无相关性(P>0.05)。结论UGT1A1*6基因多态性是一个能够预测伊立替康化疗后所导致的毒性作用,尤其是中性粒细胞减少和腹泻发生风险的分子标志物,在白细胞减少发生风险方面也有一定的意义。
基金Supported by National Natural Science Foundation Project,Grants No.30971579Capital Development Foundation,No.2007-2029
文摘Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.
文摘伊立替康(irinotecan)不良反应与UGT1A1*6单核苷酸多态性相关,目前应用的单核苷酸多态性检测方法具有耗时长、开盖易污染、操作繁琐等缺点,因此需建立一种操作简便且不易污染的适合临床应用的新方法。本研究利用3种已知基因型的DNA样本建立基于级联核酸侵入反应的real-time PCR法检测UGT1A1*6多态性的最佳反应体系,并对其检测口腔咽拭子样本的灵敏度和准确性进行了考察。结果显示,本文成功建立了基于级联核酸侵入反应的UGT1A1*6基因多态性检测方法,可用于咽拭子样本的分型检测,其灵敏度达到6 ng DNA,分型准确性达到100%。因其取样方便对人体无创,单管闭管检测不易产生交叉污染,具有用于临床检测伊立替康的个体化用药相关UGT1A1*6基因多态性的潜力。
