UGT1A1基因多态性对进展期结直肠癌患者CPT-11治疗的疗效及毒副反应的影响  被引量:2

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作  者:李建华 陈莉莉[1] 唐小万[1] 章展[1] 黄辉 杨巧 

机构地区:[1]浙江省台州市第一人民医院肿瘤内科,318020

出  处:《浙江临床医学》2018年第8期1338-1340,共3页Zhejiang Clinical Medical Journal

基  金:浙江省台州市市级科技资金项目(121ky10)

摘  要:目的探讨尿苷二磷酸葡萄醛酸转移酶1A1(UGT1A1)基因多态性对进展期结直肠癌(CRC)患者伊立替康(CPT—11)治疗的疗效及毒副反应的影响。方法选取2015年10月至2017年1月诊治的进展期CRC患者149例为观察对象,采集各受试者外周静脉血并提取基因组DNA,采用聚合酶链式反应(PCR)扩增UGT1A1基因,测序分析UGT1A1基因型,并分析不同基因型与CPT-11治疗疗效及毒副反应之间的关系。结果UGT1A1*28野生型纯合子TA6/6、突变型杂合子TA6/7、突变型纯合子TA7/7基因型比例分别为7114%、27.52%、1.34%;UGT1A1*6位点检测到野生型纯合子GG和突变型杂合子GA两种基因型,基因型比例分别为81.21%、18.79%,未检测到突变型纯合予AA。UGT1A1*28突变型患者3-4级腹泻和3-4级中性粒细胞减少发生率分别为30.23%和27.91%,均明显高于野生型患者(P〈0.05),UGT1A1*6突变型患者3~4级中性粒细胞减少发生率为28.57%,明显高于野生型患者(P〈005)。Logistic回归分析显示,UGT1A1*28基因突变是3-4级腹泻、3~4级中性粒细胞减少发生的危险因素(OR=2.18,95%CI为1.99—239;OR=318,95%CI为2.04—4.96);UGT1A1*6突变是3~4级中性粒细胞减少发生的危险因素(OR=1.68,95%CI为1.03—2.74)。UUGT1A1*28和UUGT1A1*6各基因型患者疗效和中位肿瘤无进展生存时间比较差异无统计学意义(P〉0.05)。结论UGT1A1*28/*6位点多态性可有效预测进展期CRC患者CPT—11所致3级以上腹泻和3级以上中性粒细胞减少的发生率,而与CPT-11治疗疗效无关。Objective To investigate the influence of uridine two phosphate glyoxylate transferase 1A1 ( UGT1A1 ) gene polymorphism on the curative effect and the toxic and side effects in the treatment of irinotecan (CPT-11 ) of progressive stage colorectal cancer (CRC) patients. Methods One hundred and forty-nine cases of progressive stage CRC patients treated in our hospital from October 2015 to January 2017 were selected as the research objects, peripheral blood samples were collected from all subjects and genomic DNA was extracted, Polymerase chain reaction ( PCR ) was used to amplify UGT1A1 gene, the UGT1A1 genotype was sequencing analyzed, the relationship between different genotypes and the efficacy and toxic and side effects of CPT- 11 treatment was analyzed. Results The genotype proportions of wild type homozygous TA6/6, mutant heterozygote TA6/7 and mutant homozygote TA7/7 in UGT1A1*28 were 71.14%, 27.52% and 1.34% respectively, two genotypes of wild type homozygous GG and mutant heterozygous GA were detected at UGT1A1*6 locus, and the genotype proportions were 81.21% and 18.79% respectively, mutant homozygote AA was not detected. The incidence of grade 3~4 diarrhea and 3~4 neutropenia in UGT1A1*28 mutation patients were 30.23% and 27.91% respectively and significantly higher than that in the wild type patients (P〈0.05) , the incidence of grade 3~4 neutropenia in UGT1A1*6 mutation patients was 28.57% and significantly higher than that in wild type patients (P〈0.05) . Logistic regression analysis showed that UGT1A1*28 gene mutation was a risk factor of grade 3-4 diarrhea and grade 3-4 neutropenia (OR=2.18, 95%CI was 1.99-2.39; OR=3.18, 95%CI was 2.04-4.96 ) ; UGT1A1*6 mutation was a risk factor for grade 3-4 neutrophil depletion (OR=1.68, 95%CI was 1.03-2.74 ) . There was no significant difference between the efficacy of UUGT1Al*28 and UUGT1A1*6 genotypes and the progression free survival time of the median tumor (P〉0.05) . Conelusion The polymorphism

关 键 词:尿苷二磷酸葡萄醛酸转移酶1A1 基因多态性 结直肠癌 CPT-1 1疗效 毒副反应 

分 类 号:R979.1[医药卫生—药品]

 

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