UGT1A1基因多态性与伊立替康治疗晚期结直肠癌毒性和疗效的关系

目的：探讨UGT1A1＊28/＊6基因多态性与伊立替康治疗晚期结直肠癌的毒性和疗效的关系。方法：选取2011年6月–2013年6月在我科治疗的晚期结直肠癌患者,共计102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有无差异。结果：不同UGT1A1＊28/＊6基因型患者中3~4级中性粒细胞减少和迟发性腹泻发生率无显著差异。联合UGT1A1＊28和＊6两位点分析,野生型、单点变异型和双点变异型患者中3~4级中性粒细胞减少发生率逐渐升高,三者有显著差异且升高趋势有统计学意义（4.3%、17.4%、57.1%,P=0.005,趋势检验P=0.002）。UGT1A1＊28基因型对治疗有效率（RR）和疾病控制率（DCR）无显著影响,但UGT1A1＊6基因突变者较野生型者RR、DCR均明显降低（P=0.023,P=0.032）。联合两位点分析,野生型、单点变异型和双点变异型患者RR、DCR均有显著差异（P=0.002,P=0.008）,且DCR降低趋势有统计学意义（95.7%、73.9%、42.9%,趋势检验P=0.001）。结论：在预测伊立替康毒性及疗效时,联合检测UGT1A1＊28/＊6两位点基因较单独检测一个位点更有价值。

The relationship between UGT1A1 gene polymorphisms and the toxicity and efficacy of irinotecan-based chemotherapy in advanced colorectal cancer

Objective： To evaluate the correlations between UGT1A1＊28/＊6 gene polymorphisms and irinotecan-associated toxicity and efficacy in treatment of advanced colorectal cancer. Methods： The UGT1A1＊28/＊6 genotypes of 102 advanced colorectal cancer patients treated in our department from June 2011 to June 2013 were detected. The toxicity and efficacy were observed and recorded after irinotecan-based chemotherapy. The difference of toxicity and efficacy among patients with different genetic polymorphisms were assessed. Results： There was no significant difference in the incidence of Grade 3 – 4 neutropenia and delayed-onset diarrhea among the patients with different UGT1A1＊28 and UGT1A1＊6 genotypes. When UGT1A1＊28/＊6 genotypes were analyzed simultaneously, the patients with double allele mutations had significantly higher incidence of Grade 3 – 4 neutropenia than those with single allele mutation or wild type（57.1%, 17.4%, 4.3%, respectively; Fisher＇s exact test P = 0.005; Cochran-Armitage trend test P = 0.002）. UGT1A1＊28 genotype had no effect on response rate（RR） and disease control rate（DCR）, while the patients with UGT1A1＊6 mutation showed worse efficacy（RR and DCR） than those with wild genotype（P = 0.023, P = 0.032）. When conjoint analysis of the effect of UGT1A1＊28/＊6, the differences of RR and DCR were significant in patients with wild type, single and double allele mutation（Fisher＇s exact test P = 0.002,P = 0.008）, and DCR had a decreased trend with the increase of mutant alleles（95.7%, 73.9%, 42.9%, respectively; Cochran-Armitage trend test P = 0.001）. Conclusion： Joint detection of UGT1A1＊28 and UGT1A1＊6 genotype is of more value in prediction of irinotecan-related toxicity and efficacy than single allele detection.