UGT1A1基因多态性与伊立替康治疗晚期非小细胞肺癌毒性和疗效的关系

Toxicity and efficacy relationship between UGT1A1 gene polymorphisms and irinoteca-based chemotherapy in non-small cell lung cancer

目的探讨UGT1A1＊28/＊6基因多态性与伊立替康治疗晚期非小细胞肺癌（NSCLC）的毒性和疗效的关系。方法选取2012年9月至2014年9月在皖南医学院附属弋矶山医院治疗的晚期非小细胞肺癌患者86例,对其进行UGT1A1＊28/＊6基因检测,随访记录患者行伊立替康化疗后的不良反应和近期疗效,比较不同基因型患者之间的差异。结果 UGT1A1＊28基因型患者中3～4级中性粒细胞减少发生率有统计学差异（Fisher＇s exact test,P=0.013）,3～4级迟发性腹泻未见明显统计学差异。联合UGT1A1＊28/＊6两位点分析,野生型、单点变异型和双点变异型3～4级中性粒细胞减少发生率有统计学差异,且呈逐渐升高趋势,趋势有统计学差异（2.27%、17.65%、62.5%,趋势检验P=0.001）。UGT1A1＊28和＊6基因型对治疗有效率RR和疾病控制率DCR均无显著影响。联合UGT1A1＊28/＊6两位点分析,野生型、单点变异型和双点变异型患者RR、DCR均有统计学差异（RR：P=0.007,DCR：P=0.016）,且呈逐渐降低趋势,趋势有统计学意义（RR：38.64%、8.82%、12.5%,趋势检验P=0.005。DCR：90.91%、79.41%、50.00%,趋势检验P=0.006）。结论联合检测患者UGT1A1＊28/＊6基因多态性对于伊立替康个体化治疗晚期非小细胞肺癌具有一定的临床意义。

Objective To investigate the relationship between UGT1A1＊ 28 /＊ 6 gene polymorphisms and irinotecan-associated toxicity and efficacy in treatment of non-small cell lung cancer. Methods The UGT1A1＊ 28 / ＊ 6 gene types of 86 non-small cell lung cancer patients treated in Yijishan Hospital of Wannan Medical College from Sep. 2012 to Sep. 2014 were recruited. The toxicity and efficacy among patients with different genetic polymorphisms were assessed. Results There was significant difference in the incidence of Grade 3 ～ 4 neutropenia among the patients with different UGT1A1＊ 28 genotypes,but no statistical difference in the incidence of Grade 3 ～ 4 delayed-onset diarrhea. To combination detection of UGT1A1＊ 28 and UGT1A1＊ 6,the patients with double allele mutations had significantly higher incidence of Grade 3 ～ 4 neutropenia than that with single allele mutation or wild type（ 62. 5%,17. 65%,2. 27%,respectively; Fisher＇s exact test P = 0. 001;Cochran-Armitage trend test P = 0. 001）. The response rate（ RR） and disease control rate（ DCR） of UGT1A1＊28 or UGT1A1＊ 6 were no significant differences. When conjoint analysis of the effect of UGT1A1＊ 28 / ＊ 6,the differences of RR and DCR were significant in patients with different genetypes. They also had a decreased trend with the increase of mutant genes（ RR： 38. 64%,8. 82%,12. 5%,Cochran-Armitage trend test P = 0. 005.DCR： 90. 91%,79. 41%,50. 00%,Cochran-Armitage trend test P = 0. 006）. Conclusions Joint detection the UGT1A1＊ 28 / ＊ 6 gene polymorphism with CPT-11 individualized therapy has certain clinical significance in non-small cell lung cancer patients.