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[中国结直肠癌患者UGT1A基因多态性与伊立替康毒性]

[Polymorphisms of UGT1A gene and irinotecan toxicity in Chinese colorectal cancer patients].

作者信息

Wang Yan, Xu Jian-Ming, Shen Lin, Xu Nong, Wang Jin-Wan, Jiao Shun-Chang, Zhang Jing-Sheng, Song San-Tai, Li Jian, Bao Han-Ying, Yang Lin, Li Fang

机构信息

Cancer Center, 307 Hospital, Academy of Military Medical Sciences, Beijing 100071, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2007 Dec;29(12):913-6.

PMID:18478930
Abstract

OBJECTIVE

To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecan toxicity in colorectal cancer patients.

METHODS

70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing.

RESULTS

14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancer patients and healthy subjects.

CONCLUSION

Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.

摘要

目的

评估中国人群中UGT1A基因的多态性,并探讨UGT1A基因多态性与结直肠癌患者伊立替康毒性之间的相关性。

方法

70例晚期结直肠癌患者接受伊立替康和5-氟尿嘧啶治疗。对所有这些患者和100名健康受试者进行多态性分析。从外周血中提取基因组DNA,采用聚合酶链反应和直接测序进行基因分型。

结果

14例患者出现3-4级中性粒细胞减少(20.0%),16例患者出现2-4级腹泻(22.9%),其中仅4例患者出现3-4级腹泻(5.7%)。与TA6/7和TA7/7相比,UGT1 A1 * 28野生基因型TA6/6与毒性降低显著相关(42.1%对15.7%,P = 0.027)。结直肠癌患者和健康受试者之间UGT1A基因型分布无显著差异。

结论

由于UGT1A A1 * 28野生基因型TA6/6的频率较高,中国患者伊立替康相关腹泻较少。

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