Bai Yu, Wu Hai-Wei, Ma Xu, Liu Ying, Zhang Yan-Hua
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
Onco Targets Ther. 2017 Jun 19;10:3071-3081. doi: 10.2147/OTT.S137644. eCollection 2017.
A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 () / gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type.
Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81). Blood samples for detecting were collected from each patient after various administration regimens.
Colorectal cancer patients with the mutant genotype had a significantly higher risk of severe delayed diarrhea than that of wild-type individuals when administered a CPT-11 dose ≥130 mg/m (=0.042); the same phenomenon was observed when the and mutant genotypes were considered together (=0.028). However, in lung cancer patients administered a low dose of CPT-11, / variants were not significantly associated with severe neutropenia or delayed diarrhea. Furthermore, adult patients with the mutation were more likely to develop severe delayed diarrhea than did wild-type adults (=0.013); however, the difference was not significant in elderly patients. No significant differences in tumor response were found among the different genotypes (>0.05).
Thus, age and tumor type influence our ability to predict adverse reactions based on gene polymorphisms in cancer patients. Further, gene polymorphisms are not correlated with the efficacy of CPT-11-based regimens.
进行一项回顾性研究，以分析尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）基因多态性与基于伊立替康（CPT-11）的化疗相关不良反应之间的关系。还分析了UGT1A1多态性与CPT-11临床疗效之间的相关性，以及年龄和肿瘤类型的影响。
纳入2015年4月至2016年9月在北京癌症医院接受基于CPT-11方案治疗的患者（n = 81）。在各种给药方案后，从每位患者采集用于检测UGT1A1的血样。
当给予CPT-11剂量≥130mg/m²时，携带UGT1A1突变基因型的结直肠癌患者发生严重延迟性腹泻的风险显著高于野生型个体（P = 0.042）；当同时考虑UGT1A1和UGT1A7突变基因型时，也观察到相同现象（P = 0.028）。然而，在接受低剂量CPT-11治疗的肺癌患者中，UGT1A1/UGT1A7变异与严重中性粒细胞减少或延迟性腹泻无显著相关性。此外，携带UGT1A1突变的成年患者比野生型成年患者更易发生严重延迟性腹泻（P = 0.013）；然而，在老年患者中差异不显著。不同基因型之间的肿瘤反应无显著差异（P>0.05）。
因此，年龄和肿瘤类型影响我们基于癌症患者UGT1A1基因多态性预测不良反应的能力。此外，UGT1A1基因多态性与基于CPT-11方案的疗效无关。
