UGT1 A1基因启动子区多态性与伊立替康化疗不良反应关系的研究？

目的研究尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1）基因启动子区多态性与伊立替康化疗不良反应之间的关系。方法选取本院以伊立替康为基础的化疗方案的恶性肿瘤患者212例,观察记录化疗期间患者出现不良反应（中性粒细胞减少和迟发性腹泻）的情况,并抽取外周血检测 UGT1 A1基因启动子区的多态性,统计分析 UGT1 A1基因启动子区多态性与伊立替康化疗期间不良反应的关系。结果212例患者中,181例（85.4%）基因型为 UGT1A1（6/6）,31例（14.6%）基因型为 UGT1A1（6/7）,未检测到 UGT1A1（7/7）基因型。以上两组患者发生Ⅲ~Ⅳ级中性粒细胞减少者分别为24例（13.3%）和6例（19.4%）,两者相比较差异无显著性（P=0.368）,发生Ⅲ度和Ⅳ度腹泻者分别为19例（10.5%）和9例（29%）,两者相比较差异有显著性（P =0.005）。结论与 UGT1A1（6/6）基因型相比,UGT1A1（6/7）基因型可明显增加恶性肿瘤患者在伊立替康化疗时发生Ⅲ~Ⅳ度腹泻的风险,但不会增加患者Ⅲ~Ⅳ级中性粒细胞减少的风险。临床检测 UGT1 A1基因启动子区多态性可以预测伊立替康化疗不良反应的发生。

Study on the Relationship Between UGT1A1 Gene Promoter Polymorphism and Adverse Events of Irinotecan-based Chemotherapy

Obj ective]To investigate the relationship between uridine diphosphoglucuronic acid transferase （UGT1 A1 ）gene promoter polymorphism and adverse events of irinotecan-based chemotherapy.[Methods]Totally 2 1 2 patients with malignant tumor receiving irinotecan-based chemotherapy regimen in our hospital were chosen.Adverse e-vents（neutropenia and late-onset diarrhea）during chemotherapy were recorded.Peripheral blood was extracted to examine UGT1 A1 gene promoter polymorphism,and its relationship with adverse events during irinotecan-based chemotherapy was analyzed.[Results]Of 212 patients,181 patients（85.4%）were UGT1A1（6/6）genotype,and 31 patients（14.6%） were UGT1A1（6/7）genotype,and no UGT1A1（7/7）genotype was found.In above two groups,gradeⅢandⅣ neu-tropenia occurred in 24 patients（13.3%）and 6 patients（19.4%）respectively,but there was no significant difference be-tween them（P=0.368）.More than gradeⅢdiarrhea occurred in 19 patients（10.5%）and 9 patients（29%）respectively in two groups,and there was significant difference between them（P=0.005）.[Conclusion]Compared with UGT1A1 （6/6）genotype,UGT1A1（6/7）genotype can obviously increase the risk of the occurrence of gradeⅢandⅣdiarrhea in patients with malignant tumor during irinotecan-based chemotherapy,but not increase the risk of the occurrence of gradeⅢandⅣ neutropenia of patients.Clinical detection of UGT1 A1 gene promoter polymorphism can predict the occurrence of adverse events of irinotecan-based chemotherapy.