中国人UGT1A1*28的基因多态性以及与伊立替康毒性和疗效的关系

“…【目的】研究中国肿瘤患者UGT1A1*28的基因多态性与伊立替康的化学治疗在进展期消化道肿瘤患者不良反应的发生率和严重程度的关系【方法】采用PCR法扩增目的基因片段,直接测序法分析UGT1A基因多态性的方法,检测2010年3月至2011年3月在我院住院治疗的317例肿瘤患者UGT1A1基因多态性的分布情况,并对其中44例采用含伊立替康方案化疗的进展期胃肠肿瘤患者,观察并记录化疗中出现的不良反应情况,比较不同基因型患者使用伊立替康后Ⅲ度以上不良反应发生率的差异【结果】317例恶性肿瘤患者中UGT1A1基因启动子区TA序列6次重复的纯合野生型TA6/6有250例(78.9%);基因型为TA序列6次和7次重复的杂合型TA6/7有59例(18.6%);基因型TA序列7次重复的纯合突变型TA7/7有8例(2.5%)在44例采用含伊立替康方案化疗的进展期胃肠肿瘤患者中,TA6/6TA6/7和TA7/7各基因型发生Ⅲ度以上中性粒细胞减少者分别为8.6%12.5%和100%;发生Ⅲ度以上腹泻者分别为14.3%12.5%和100%【结论】中国患者UGT1A1*28多态性频率低, TA7/7纯合变异型患者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增加,而TA6/7杂合子与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,对野生型TA6/6能否通过筛查,选择合适患者适当增加伊立替康剂量以提高疗效,值得临床进一步深入研究…”
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