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目的了解广泛期小细胞肺癌患者血中尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)启动子的多态性分布,并研究其多态性和伊立替康化疗不良反应、疗效之间的关系。方法收集采用伊立替康加顺铂化疗患者全血标本,直接测序分析UGT1A1*28TATA盒基因序列;并与化疗不良反应、疗效进行分析。结果 36例患者进行UGT1A1*28TATA基因启动子检测,UGT1A1*28野生纯合型(TA6/6)27例,占75%;突变杂合型(TA6/7)7例,占19.4%;突变纯合型(TA7/7)2例,占5.6%。UGT1A1基因突变纯合型(TA7/7))患者发生Ⅲ度迟发型腹泻1例,2例皆发生Ⅲ度粒细胞减少。UGT1A1基因突变杂合型(TA6/7)发生Ⅲ度迟发型腹泻1例,Ⅲ度粒细胞减少1例。UGT1A1基因野生纯合型(TA6/6)无Ⅲ度迟发型腹泻和Ⅲ度中性粒细胞减少发生,Ⅰ~Ⅱ度迟发型腹泻3例,Ⅰ~Ⅱ度粒细胞减少5例。全部患者未发生Ⅲ度以上恶心、呕吐、食欲不振、乏力、腹泻等不良反应。UGT1A1基因突变纯合型(TA7/7))CR 0例,PR 1例;UGT1A1基因突变杂合型(TA6/7)CR 1例,PR 3例;UGT1A1基因野生纯合型(TA6/6)CR3例,PR 15例。结论 UGT1A1*28突变纯合型(TA7/7)可能增加伊立替康所致3度及以上延迟性腹泻和中性粒细胞减少。
Objective To investigate the polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) promoter in patients with extensive-stage small-cell lung cancer and to study its association with adverse reactions and efficacy of irinotecan chemotherapy . Methods The whole blood samples of patients with irinotecan plus cisplatin chemotherapy were collected and directly sequenced to analyze the UGT1A1 * 28 TATA box gene sequence. The adverse reactions and effects of chemotherapy were analyzed. RESULTS: The UGT1A1 * 28TATA gene promoter was detected in 36 patients, with 27 cases (75%) of UGT1A1 * 28 wild type (TA6 / 6), 7 cases of mutation heterozygous (TA6 / 7) Tailored (TA7 / 7) 2 cases, accounting for 5.6%. UGT1A1 gene mutation homozygous (TA7 / 7)) patients with Ⅲ degree delayed diarrhea occurred in 1 case, 2 cases occurred Ⅲ degree neutropenia. UGT1A1 mutation heterozygous (TA6 / 7) Ⅲ degree delayed type diarrhea occurred in 1 case, Ⅲ degree neutropenia in 1 case. UGT1A1 wild homozygous (TA6 / 6) Ⅲ degree delayed type diarrhea and Ⅲ degree neutropenia occurred, Ⅰ ~ Ⅱ degree delayed diarrhea in 3 cases, Ⅰ ~ Ⅱ degree of neutropenia in 5 cases. All patients did not occur Ⅲ degree above nausea, vomiting, loss of appetite, fatigue, diarrhea and other adverse reactions. UGT1A1 gene mutation homozygous (TA7 / 7)) CR 0 cases, PR 1 case; UGT1A1 gene mutation heterozygous (TA6 / 7) CR 1 cases, PR 3 cases; UGT1A1 gene wild type homozygous (TA6 / 6) CR3 cases, PR 15 cases. CONCLUSION: UGT1A1 * 28 mutant homozygous (TA7 / 7) may increase irinotecan-induced delayed diarrhea and neutropenia by 3 degrees and above.