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伊立替康不良反应与UGT1A1基因多态性关系的研究
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| 篇名： | 伊立替康不良反应与UGT1A1基因多态性关系的研究 |
| TITLE： | |
| 摘要： | 目的：研究应用伊立替康化疗的患者不良反应的发生率及严重程度与UGT1A1基因启动子区多态性的关系。方法：选择56例我院晚期胃肠道肿瘤和小细胞肺癌患者，使用含伊立替康的方案化疗，观察并记录患者化疗中出现的不良反应；外周血中抽提基因组DNA，测定UGT1A1基因多态性，分析基因型与不良反应的关系。结果：42例患者（75.0％）UGT1A1*28为野生型TA6/6；13例患者（23.2％）为杂合突变型TA6/7；1例患者（1.8％）为纯合突变型TA7/7；UGT1A1*6野生型有44例（78.6％），杂合突变型有10例（17.9％），纯合突变型有2例（3.6％）。UGT1A1*28野生型、突变型患者发生Ⅲ度以上白细胞和/或中性粒细胞减少者分别为6、3例（14.3％ vs. 21.4％，P＞0.01），其中纯和突变型患者发生Ⅲ度以上白细胞和/或中性粒细胞减少者为1例（100％）；发生Ⅲ度以上腹泻者分别为6、2例（14.3％ vs. 14.3％，P＞0.01），其中纯和突变型患者发生Ⅲ度以上腹泻为1例（100％）。UGT1A1*6野生型、突变型患者发生Ⅲ度以上中性粒细胞减少者分别为3、8例（6.8％ vs. 66.6％，P＜0.01），发生Ⅲ度以上腹泻者分别为2、7例（4.5％ vs. 58.3％，P＜0.01）。结论：晚期胃肠道肿瘤和小细胞肺癌患者中，UGT1A1基因野生型最为常见，杂合突变型次之，而纯合突变型很少见。 TA7/7纯合突变型患者应用伊立替康化疗发生Ⅲ度以上白细胞和/或中性粒细胞减少和腹泻的风险增加，而TA6/7杂合突变型与TA6/6野生型相似，并不增加患者发生Ⅲ度以上中性粒细胞减少和腹泻的风险。UGT1A1*6突变型应用伊立替康化疗发生Ⅲ度以上中性粒细胞减少和腹泻的风险较野生型明显增加。 |
| ABSTRACT： | OBJECTIVE： To study the correlation of UGT1A1 gene polymorphisms with the incidence and severity of irinotecan-associated ADR in the patients with irinotecan-based chemotherapy. METHODS： 56 patients with advanced gastroenteric tumor and small cell lung carcinoma were selected from our hospital and treated with irinotecan-based chemotherapy. The occurrence of ADR was observed during chemotherapy. Gene DNA were collected from peripheral blood sample， and UGT1A1 gene polymorphisms was determined. The relationship of genotypes with ADR was analyzed. RESULTS： TA sequence of UGT1A1*28 genetic locus was as follows： wild-type genotype TA6/6 （42 cases， 75.0％）， heterozygous mutation-type TA6/7 （13 cases， 23.2％） and homozygous mutation-type TA7/7 （1 cases， 1.8％）； that of UGT1A1*6 genetic locus was as follows： wild-type genotype （44 cases， 78.6％）， heterozygous mutation-type （10 cases， 17.9％） and homozygous mutation-type （2 cases， 3.6％）. In UGT1A1*28 genetic locus， 6 wild-type genotype patients and 3 mutation-type patients suffered from Ⅲ degree or above hypoleukemia and/or neutropenia （14.3％ vs. 21.4％，P＞0.01）， among which only one homozygous mutation-type patient suffered from hypoleukemia and/or neutropenia （100％）； 6 wild-type genotype patients and 2 mutation-type patients suffered from Ⅲ degree or above diarrhea （14.3％ vs. 14.3％， P＞0.01）， among which only one homozygous mutation-type patient suffered from Ⅲ degree or above diarrhea （100％）. In UGT1A1*6 genetic locus， 3 wild-type genotype patients and 8 mutation-type patients suffered from Ⅲ degree or above neutropenia （6.8％ vs. 66.6％，P＜0.01）， and 2 wild-type genotype patients and 7 mutation-type patients suffered from Ⅲ degree or above diarrhea （4.5％ vs. 58.3％，P＜0.01）. CONCLUSIONS： Among patients with advanced gastroenteric tumor and small cell lung carcinoma， UGT1A1 gene wild-type gene promoter is most common， followed by heterozygous mutation-type， and homozygous mutant rare. For TA7/7 homozygous mutation-type patients， irinotecan-based chemotherapy increase the risk of Ⅲ degree or above hypoleukemia and/or neutropenia and diarrhea. For TA6/7 heterozygotes patients and TA6/6 wild-type patients， irinotecan-based chemotherapy doesn’t affect the incidence of Ⅲ degree or above neutropenia and diarrhea. For UGT1A1*6 genetic locus mutation-type patients， irinotecan-based chemotherapy significantly increase the risk of Ⅲ degree or above neutropenia and diarrhea. |
| 期刊： | 2016年第27卷第5期 |
| 作者： | 游云红，王颂平，朱超，柴洁 |
| AUTHORS： | YOU Yunhong，WANG Songping，ZHU Chao，CHAI Jie |
| 关键字： | 伊立替康；药品不良反应；UGT1A1；基因多态性 |
| KEYWORDS： | Irinotecan； Adverse drug reaction； UGT1A1； Gene polymorphism |
| 阅读数： | 627 次 |
| 本月下载数： | 8 次 |
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