部分由于严重的药物不良反应(ADR),化疗药物在肺癌治疗中的应用不足。
随着研究揭示患者间ADR变异与外排转运体变异之间的关联,我们进行了荟萃分析和系统综述,为了强调当前有关外排转运蛋白SNP变体与化疗药物诱导的ADR之间关联强度的知识。
论文来自MEDLINE,科克伦图书馆,CINHL,EMBASE,WebofKnowledge,Scopus.Cochrane协作偏差风险工具v13用于评估每种审查的出版物的六种类型的偏差域。
二十五份出版物,包括三项随机对照试验,两项回顾性病例对照和20项临床观察研究,共有3578名患者,被认为有资格审查。在已知的外排药物转运蛋白中,我们报告了ABC成员ABCB1,ABCC1,ABCC2,ABCG2,ABCA1,ABCC4和ABCC5的研究结果.Meta分析显示,在表达ABCB12677G>T/G的患者中,伊立替康诱导的中性粒细胞减少的风险降低(比值比[OR]:0.24;95%CI:0.1-0.59;p=0.002),但ABCC23972T>T的风险增加(OR:1.67;95%CI:1.01-2.74;p=0.04)。ABCG234G>A与伊立替康引起的腹泻风险增加三倍相关(95%CI:1.00-6.24;p=0.05)。
大多数研究已经确定了高效药物转运体变异体在肺癌治疗相关ADR中的作用。然而,为了实施使用这些转运蛋白遗传变异作为ADR风险的预后标志物,未来的研究必须纳入更大的患者数量.
Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs).
With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic
review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs.
Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed.
Twenty-five publications comprising three randomised control trials, two retrospective case-controls and 20 clinical observation studies, totalling 3578 patients, were deemed eligible for
review. Of the known efflux drug transporters, we report findings on the ABC members
ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing
ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04). ABCG2 34G>A was associated with a threefold increased risk of irinotecan-induced diarrhea (95% CI: 1.00-6.24; p = 0.05).
The majority of studies have identified a role for variants in effluxdrug transporters in contributing to lung cancer treatment-associated ADRs. However, for implementation of use of these transporter genetic variants as prognostic markers for ADR risk, future studies must incorporate larger patient numbers.