吕雅蕾, 刘巍, 杜玉娟, 冯莉, 王玉栋, 王龙. UGT1A1基因多态性与伊立替康安全性和有效性的临床研究[J]. 中国肿瘤临床, 2012, 39(20): 1542-1546. DOI: 10.3969/j.issn.1000-8179.2012.20.022
引用本文: 吕雅蕾, 刘巍, 杜玉娟, 冯莉, 王玉栋, 王龙. UGT1A1基因多态性与伊立替康安全性和有效性的临床研究[J]. 中国肿瘤临床, 2012, 39(20): 1542-1546. DOI: 10.3969/j.issn.1000-8179.2012.20.022
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Yalei LV, Wei LIU, Yujuan DU, Li FENG, Yudong WANG, Long WANG. Clinical Study of the Correlation between UGT1A1 Polymorphism and the Safety and Efficacy of Irinotecan[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(20): 1542-1546. DOI: 10.3969/j.issn.1000-8179.2012.20.022
Citation: Yalei LV, Wei LIU, Yujuan DU, Li FENG, Yudong WANG, Long WANG. Clinical Study of the Correlation between UGT1A1 Polymorphism and the Safety and Efficacy of Irinotecan[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(20): 1542-1546. DOI: 10.3969/j.issn.1000-8179.2012.20.022
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UGT1A1基因多态性与伊立替康安全性和有效性的临床研究

Clinical Study of the Correlation between UGT1A1 Polymorphism and the Safety and Efficacy of Irinotecan

    摘要
  • 摘要:
      目的  观察57例应用伊立替康治疗进展期消化道肿瘤患者的安全性和有效性。
      方法  采用全血基因组DNA提取、PCR法扩增目的基因片段, 直接测序法分析UGT1A1基因多态性, 检测2011年8月至2012年6月在河北医科大学第四医院肿瘤内科住院治疗的57例进展期消化道肿瘤患者应用伊立替康的情况, 观察并记录化疗中出现的不良反应以及疗效。
      结果  57例进展期消化道肿瘤患者中, UGT1A1基因启动子区28位点, TA序列6次重复的纯合野生型TA6/6有43例（75.4%）; 基因型为TA序列6次和7次重复的杂合型TA6/7有13例（22.8%）; 基因型为TA序列7次重复的纯合突变型TA7/7有1例（1.8%）。UGT1A1基因启动子区6位点野生型G/G有48例（84.2%）, 杂合突变型G/A有7例（12.3%）, 纯合突变型A/A有2例（3.5%）。在57例采用含伊立替康方案化疗的进展期消化道肿瘤患者中, UGT1A1基因启动子区28位点, TA6/6、TA6/7和TA7/7野生型和突变型发生3级以上中性粒细胞减少者分别为7.0%、14.3%, 发生3级以上腹泻者分别为9.3%、14.3%, 其中纯合突变型仅1例患者, 100%的发生率。UGT1A1基因启动子区6位点, G/G、G/A和A/A野生型和突变型发生3级以上中性粒细胞减少者分别为4.2%、55.6%, 发生3级以上腹泻者分别为12.5%、44.4%, 具有统计学差异。各组之间疗效无统计学差异。
      结论  患者UGT1A1*28和UGT1A1*6多态性分布基本一致, UGT1A1*6突变型患者应用伊立替康化疗发生3级以上中性粒细胞减少和腹泻的风险增加, 而UGT1A1*28突变型与以上不良反应并无绝对相关性, UGT1A1各基因型之间疗效无明显差异。能否通过对UGT1A1的筛查, 选择合适患者安全有效的应用伊立替康, 值得临床进一步扩大样本量深入研究。

     

    Abstract:
      Objective  The objective of this study was to investigate the relationship between UGT1A1 polymorphism and the safety and efficacy of irinotecan chemotherapy in patients with advanced gastrointestinal carcinoma.
      Methods  UGT1A1 genetic polymorphism was analyzed by direct sequencing analysis using genomic DNA extraction and PCR assay to amplify the target gene fragment in 57 patients with advanced gastrointestinal cancer receiving irinotecan-based chemotherapy. The adverse events and results of every clinical evaluation during treatment were recorded. Differences in the incidence of grades 3 and 4 adverse events were compared.
      Results  Of the 57 case patients included in this study, 43 (75.4%) were identified as having homozygous wild-type TA6/6 in the promoter region at position 28 of the UGT1A1 gene, 13 (22.8%) were found to have heterozygous type TA6/7, and 1 (1.8%) carried homozygous mutant-type TA7/7. By contrast, 48 case patients (84.2%) were identified as having homozygous wild-type G/G in the promoter region at position 6 of the UGT1A1 gene, 7 (12.3%) were found to have heterozygous mutant-type G/A, and 2 (3.5%) carried homozygous mutant-type A/A. The incidence rates of grade 3 neutropenia and diarrhea or higher were 7.0% in patients with wild-type TA6/6 versus 14.3% in patients with mutant-type TA6/7 and 9.3% in patients with wild-type TA6/6 versus 14.3% in the patient with mutant-type TA7/7. On the other hand, the incidence rates of grade 3 neutropenia and diarrhea or higher were 4.2% in patients with wild-type G/G versus 55.6% in patients with mutant-type G/A and 12.5% in patients with wild-type G/G versus 44.4% in patients with mutant-type A/A. The response rates among all groups did not statistically differ.
      Conclusion  Patients with UGT1A1*28 polymorphism are similar to those with UGT1A1*6 polymorphism. The risk of having neutropenia and diarrhea higher than grade 3 was higher in patients with the UGT1A1*6 mutant genotype, whereas no absolute correlation was observed for those with the UGT1A1*28 mutant genotype. Use of UGT1A1 polymorphism screening to select the right patients with the appropriate dose of irinotecan should be further investigated to improve the efficacy of the drug.

     

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