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目的观察尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1*)6和UGT1A1*28基因多态性与伊立替康化疗疗效及不良反应之间的关系。方法采用外周静脉血DNA抽提、聚合酶链反应(PCR)扩增和焦磷酸测序方法分析UGT1A1*6和UGT1A1*8基因型,收集72例2010年1月至2013年12月间接受伊立替康治疗的晚期恶性肿瘤患者的临床资料,观察患者用药期间的药物不良反应及化疗疗效,分析基因多态性与化疗不良反应及近期疗效的关系。结果 72例恶性肿瘤(结直肠癌、小细胞肺癌)患者中,UGT1A1*6野生型G/G 40例(55.6%),杂合突变型G/A 21例(29.2%),纯合突变型A/A 11例(15.2%);UGT1A1*28野生型(TA)6/(TA)651例(70.8%),杂合突变型(TA)6/(TA)720例(27.8%),纯合突变型(TA)7/(TA)71例(1.4%)。UGT1A1*6突变型患者(G/A和A/A)3~4级腹泻和3~4级中性粒细胞减少的发生率分别为65.6%和43.7%,野生型(G/G)分别为30.0%和17.5%,差异均有统计学意义(均P<0.05)。UGT1A1*28突变型患者[(TA)6/(TA)7和(TA)7/(TA)7]3~4级腹泻的发生率(42.9%)高于野生型(17.6%,P<0.05)。各组之间近期化疗疗效差异无统计学意义(P>0.05)。结论 UGT1A1*6突变型患者应用伊立替康化疗发生3级及以上中性粒细胞减少及迟发性腹泻的风险增加,而UGT1A1*28突变型患者发生3级以上迟发性腹泻的风险增加,UGT1A1各基因型之间疗效无明显差异,通过检测UGT1A1基因多态性能够合理选择应用伊立替康。
Objective To investigate the relationship between the polymorphisms of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1 *) 6 and UGT1A1 * 28 and the efficacy and adverse reactions of irinotecan chemotherapy. Methods The genotypes of UGT1A1 * 6 and UGT1A1 * 8 were analyzed by peripheral venous blood DNA extraction, polymerase chain reaction (PCR) amplification and pyrosequencing method. Seventy-two patients were enrolled from January 2010 to December 2013, Kang treatment of advanced malignant tumors in patients with clinical data to observe the drug adverse reactions during chemotherapy and chemotherapy efficacy, analysis of genetic polymorphisms and adverse reactions and the relationship between the short-term efficacy of chemotherapy. Results Among 72 malignant tumors (colorectal cancer and small cell lung cancer), UGT1A1 * 6 wild type G / G was found in 40 (55.6%) and heterozygous mutant G / A in 21 (29.2%), homozygous mutant There were 11 cases (15.2%) in A / A, 651 cases (70.8%) of wild-type UGT1A1 * 28 WT (TA) and 720 cases (27.8%) of TA heterozygous TA / Combined mutation (TA) 7 / (TA) in 71 cases (1.4%). The prevalences of grade 3 to 4 diarrhea and grade 3 to 4 neutropenia in UGT1A1 * 6 mutant patients (G / A and A / A) were 65.6% and 43.7%, respectively. The wild type (G / G) 30.0% and 17.5%, respectively (all P <0.05). The prevalence of Grade 3-4 diarrhea (42.9%) was significantly higher in the patients with UGT1A1 * 28 mutation than those in the wild type (17.6%, P <0.05) [(TA) 6 / (TA) 7 and (TA) 7 / (TA) ). There was no significant difference in the curative effect between the two groups (P> 0.05). Conclusion The risk of neutropenia and delayed diarrhea in patients with UGT1A1 * 6 mutant with irinotecan chemotherapy is higher than that in patients with UGT1A1 * 6 mutation, while the risk of delayed diarrhea with grade 3 or higher in UGT1A1 * 28 mutant patients is increased, There was no significant difference between the two genotypes of UGT1A1, and irinotecan could be rationally selected by detecting UGT1A1 gene polymorphism.