UGT1A1基因多态性与转移性结直肠癌伊立替康化疗毒性及疗效的关系

摘要

AIM: To invesligale the correlation of UGT1A1 * 28 and UGT1A1 * 6 gene polymorphisms with irino-tecan - associated adverse evenls and efficacy in the palienls with metastatic colorectal cancer (mCRC) trealed with irinole-can - based chemolherapy. METHODS: Analysis of UGT1A1 * 28 and UGT1A1 * 6 gene polymorphisms was performed in 207 gaslroinleslinal cancer palienls admilled to our hospital from April 2010 to March 2012 by amplifying the gene frag-ments using PCR and direcl sequencing. Fifty six cases wilh mCRC trealed wilh irinolecan were chosen lo observe the adverse evenls and efficacy during chemolherapy, and the lime lo progression (TTP) was also recorded. The incidence of dif-ferenl genolypes was compared. RESULTS: The distribution of the genolypes in 207 gaslroinleslinal cancer palienls was as follows: UGT1A1 * 28 wild - type ( WT) genolype TA6/6 ( 164 , 79. 2% ) , helerozygous genolype TA6/7 (41, 19.8%), and homozygous genolype TA7/7 (2, 1. 0% ) ; UGT1A1 * 6 WT genolype G/G ( 154, 74. 4% ) , helerozygous genolype G/ A (51, 24.6%), and homozygous genolype A/A (2, 1.0%). In the 56 mCRC cases, the incidence of grade 3 and 4 delayed diarrhea and neulropenia in the palienls carrying UGT1A1 *6 ( G/A and A/A) was higher than that in the WT genolype (6/6) (38.9% vs 7.9% ,61. 1% vs 29.0% , both P<0.05). The incidence of grade 3 and 4 thrombocylopenia in the palienls carrying UGTIAI* 28 (TA6/7 and TA7/7) was higher lhan lhal in the WT genolype (TA6/6) (33.3% vs 2. 1 % , P < 0. 05 ) . No significant difference of TTP and chemotherapeutic effect was observed belween different genotypes. CONCLUSION: The UGT1A1 * 6 ( G/A and A/A) genolypes increase the risk of grade 3 and 4 delayed diarrhea and neu-tropenia, and the UGT1A1*28 (TA6/7 and TA7/7 ) genolypes increase the risk of grade 3 and 4 thrombocylopenia in mCRC palients trealed with irinolecan - based chemotherapy.%目的:探讨UGT1A1*28和UGT1A1*6基因多态性与伊立替康治疗转移性结直肠癌患者的不良反应和疗效之间的关系.方法:外周血中抽提基因组DNA,采用PCR扩增目的基因片段,直接测序法分析2010年4月至2012年3月在我院做基因检测的207例消化道肿瘤患者UGT1A1*28和UGT1A1*6基因多态性的分布情况,并对其中56例采用含伊立替康方案化疗的转移性结直肠癌患者出现的不良反应情况、肿瘤进展时间及化疗疗效进行观察并记录,比较不同基因型患者之间的差异.结果:207例消化道肿瘤患者中,UGT1A1*28位点野生型TA6/6有164例(79.2%),杂合突变型TA6/7有41例(19.8%),纯合突变型TA7/7有2例(1.0%);UGT1A1*6位点野生型G/G有154例(74.4%),杂合突变型G/A有51例(24.6%),纯合突变型A/A有2例(1.0%).在56例转移性结直肠癌患者中,*6位点突变型(G/A和A/A)可以增加发生3级以上腹泻(38.9% vs 7.9%,P<0.05)和中性粒细胞减少(61.1% vs 29.0%,P<0.05)的风险;*28位点突变型(6/7和7/7)可以增加发生3级以上血小板减少(33.3% vs 2.1%,P<0.05)的风险;肿瘤进展时间和化疗疗效在*28和*6位点各基因型之间差异无统计学意义.结论:在采用含伊立替康方案化疗的转移性结直肠癌患者中,UGT1A1*6位点突变型增加发生3级以上腹泻和中性粒细胞减少的风险;UGT1A1*28位点突变型增加发生3级以上血小板减少的风险.