UGT1A1*6基因多态性与伊立替康毒性关系的meta分析

Association of UGT1A1*6 Polymorphisms with Irinotecan-induced Toxicities:A Meta-analysis

目的 通过整合相关文献进行meta分析以得出UGT1A1＊6基因多态性与伊立替康毒性的关系,指导临床治疗。方法通过Pub Med数据库及手工搜索相关文献,制定文章纳入排除标准,纳入文章进行质量评价,提取数据后,应用STATA12.0软件进行分析。结果 共纳入12篇文章进行分析,UGT1A1＊6突变型较野生型发生粒细胞缺乏的风险率显著提高（OR=2.37,95%CI 1.58~3.55,P=0.001）,其中纯合突变型和杂合突变型较野生型粒细胞缺乏发生风险率高,纯合突变型（OR=5.09,95%CI2.74~9.45,P〈0.001）较杂合突变型（OR=2.07,95%CI 1.37~3.13,P=0.001）风险率更高;而在腹泻方面,UGT1A1＊6突变型较野生型发生腹泻的风险率高（OR=1.48,95%CI 0.86~2.55,P=0.153）,但无统计学差异,而其中纯合突变型腹泻发生风险率显著增高（OR=3.51,95%CI 1.33~9.25,P=0.011）,杂合突变型（OR=1.22,95%CI 0.68~2.22,P=0.503）腹泻发生风险率增高,但结果无统计学差异。结论 UGT1A1＊6基因多态性可以预测伊立替康的毒性,尤其是粒细胞缺乏的发生率。

Objective To conduct a meta-analysis of literatures to explore the relationship of UGTIAl＊6gene polymorphism and irinotecan toxici- ty, so as to guide clinical treatment. Methods Papers were searched by PubMed database and manual search. The inclusion and exclusion criteria of studies were formulated and the methodologies quality was assessed, data were extracted and the statistical analysis was made using STATA12.0 software. Results A total of 12 articles were included according to the inclusion and exclusion criteria. Patients with mutated UGT1A 1＊6 showed an increased risk for neutropenia compared to wild UGT1AI＊6（ OR =2.37,95%CI 1.58-3.55, P = 0.001 ）. Both homozygous and heterozygous muta- tion showed an increased risk for neutropenia compared to wild type and the homozygous mutation （OR = 5.09,95% CI 2.74-9.45, P 〈 0.001 ） showed an even higher risk for neutropenia compared to the heterozygous mutation（ OR = 2.07,95%CI 1.37-3.13, P = 0.001 ）. For severe dian-hea, mutated UGT1AI＊6 showed an increased risk compared to wild type （ OR =1.48,95%CI 0.86-2.55, P = 0.153）, though without statistical signifi- cance. The homozygous mutation performed a significantly increased risk （ OR =3.51,95%CI 1.33-9.25, P = 0.011 ） and the heterozygous mutation also showed increased risk, however, the difference between them was not statistically significant. Conclusion UGT1AI＊6 polymorphisms can pre- dict irinotecan toxicity, especially for incidence of neutropenia.