UGTIA1基因多态性与IP方案治疗小细胞肺癌毒性和疗效相关性分析

目的：探讨尿苷二磷酸葡萄糖转移酶1A1（UGTIA1）基因多态性与伊立替康联合顺铂（IP方案）治疗广泛期小细胞肺癌的不良反应和疗效相关性。方法：选取中国医学科学院肿瘤医院2009-01-01-2012-12-31初治广泛期小细胞肺癌患者48例，采用伊立替康联合顺铂化疗方案，分析其临床治疗效果和不良反应及其与UGT1A1基因多态性的相关性。结果：48例小细胞肺癌患者IP方案化疗后CR3例，PR32例，SD4侧，PD9例，总有效率为73．0％，疾病控制率为81．3％。主要毒副作用为中性粒细胞减少34例，贫血29例，血小板减少14例，恶心呕吐38例，迟发性腹泻26例，便秘15例，脱发5例，乏力38例，转氨酶升高14例，心电图异常9例。UGT1A1＊28基因多态性的分布为TA6／6野生型基因34例，TA6／7杂合突变型基因11例，TA7／7纯合突变型基因3例；UGT1A1＊6基因多态性的分布为G／C野生型基因33例，A／G杂合突变型基因13例，A／A纯合突变型基因2例。UGT1A1基因多态性与临床疗效无明显相关性，P〉0．05。提示UGT1A1突变型基因可增加患者发生迟发性腹泻的风险，而对中性粒细胞减少无影响。Logistic多因素回归分析结果显示，UGT1A1＊28、UGT1A1＊6、ECOG评分和治疗周期数对迟发性腹泻有明显影响；同时ECOG评分和治疗周期数对中性粒细胞减少存在影响。结论：UGT1A1突变基因对患者迟发性腹泻有明显影响，UGT1A1基因多态性检测可为临床应用伊立替康联合顺铂相关不良反应的预测提供依据，对临床用药安全具有重要意义。

Analysis of relationship between the UGT1A1 gene polymorphisms and toxicity as well as efficacy in patients with small cell lung cancer treated with irinotecan

OBJECTIVE：To explore the relationship between the UGT1A1 gene polymorphisms and toxicity as well as efficacy in 48 patients with small cell lung cancer initially treated with irinotecan combined with cis-platinum regimen as first-line chemotherapy. METHODS： Forty-eight patients with previously-untreated extensive-stage small cell lung cancer were treated with irinotecan plus cis-platinum regimen. The relationships between the UGT1A1 gene polymorphisms and toxicity as well as efficacy were analyzed. RESULTS： The main side effects were 34 cases with neutropenia, 29 case with a- nemia,14 cases with thrombocytopenia,38 cases with nausea and vomiting, 26 cases with delayed diarrhea, 15 cases with constipation, 5 cases with hair loss, 38 cases with fatigue, 14 cases with transaminase elevation and 9 cases with abnormal ECG. The distribution of UGT1A1＊ 28 gene polymorphisms were as follws：34 cases with TA6/6 gene type, 11 cases with TA6/7 gene type and 3 cases with TAT/7 gene type. The distribution of UGT1A1 ＊ 6 gene polymorphisms were 33 cases with G/G gene type, 13 cases with A/G gene type and 2 cases with A/A gene type. There was no significant relationship between UGT1A1 gene polymorphisms and clinical efficacy. Mutant-type of UGT1A1 may increase the risk of delayed di- arrhea and had no influence on neutropenia. The result of multivariate Logistic regression analysis showed that the delayed diarrhea was related with UGTIA1 ＊ 28, UGT1A1 ＊ 6, ECOG and times of treatment cycles were influential on delayed diarrhea,and ECOG and times of treatment cycles were influential on neutropenia. CONCLUSIONS： Mutant-type of UGT1A1 was influential on delayed diarrhea. It is helpful to forecast adverse effect after using irinotecan and important for clinical medication safety.