UGT1A1基因多态性与伊立替康化疗的安全性评估

Risk assessment between UGT1A1 polymorphism and the safety of irinotecan

目的:观察应用伊立替康化疗治疗胃肠肿瘤的安全性。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*28基因多态性;检测2012年1月至2013年12月我院肿瘤内科收治的52例胃肠肿瘤患者应用伊立替康情况,观察并记录化疗中出现的不良反应。结果:52例胃肠肿瘤患者中,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 40例(76.9%)。基因型为TA序列6次和7次重复的杂合型TA6/7有8例(15.4%)。基因型为TA序列7次重复的纯合突变型TA7/7有4例(7.7%)。在52例采用含伊立替康方案化疗的胃肠肿瘤中,TA6/6、TA6/7+TA7/7突变型发生Ⅲ级以上腹泻、白细胞减少、中性粒细胞减少者分别为15%和25%、10%和25%、10%和25%,差异具有统计学意义。结论:在采用含伊立替康方案化疗的胃肠肿瘤患者中,UGT1A1*28位点突变型增加发生Ⅲ级以上腹泻、Ⅲ级以上白细胞减少、Ⅲ级以上中性粒细胞减少的风险。

Objective： To investigate the relationship between UGT1A1 polymorphism and the safety of irinotecan chemotherapy in patients with gastrointestinal carcinoma. Methods： UGT1A1 genetic polymorphism was analyzed by direct sequencing analysis using genomic DNA extraction and PCR assay to amplify the arget gene fragment in 40 patients with gastrointestinal cancer receiving irinotecan-based chemotherapy. Differences in the incidence of grades Ⅲand Ⅳ adverse events were compared. Results： Of the 52 patients 40（ 76. 9%） were identified as having homozygous wild-type TA6 /6 in the promoter region at position 28 of the UGT1A1 gene,8（ 15. 4%） were found to have heterozygous type TA6 /7 and 4（ 7. 7%） carried homozygous mutant-type TA7 /7. In 52 cases with gastrointestinal cancer treated with irinotecan,15%,25% had grade Ⅲ and Ⅳ diarrhea between TA6 /6 and TA6 /7 ＋ TA7 /7. 10%,25%had grade Ⅲ and Ⅳ neutroptnia and leucpenia between TA6 /6 and TA6 /7 ＋ TA7 /7. The difference was statistically significant. Conclusion： The UGT1A1＊ 28（ TA6 /7 and TA7 /7） genotypes increase the risk of grade Ⅲ and Ⅳ diarrhea / neutroptnia / leucpenia in gastrointestinal cancer treated with irinotecan-based chemotherapy.