Shanghai Institute of Materia Medica and Graduate School, Chinese Academy of Sciences, Shanghai 201203, PR China.
Eur J Cancer. 2010 Jul;46(10):1856-65. doi: 10.1016/j.ejca.2010.02.049. Epub 2010 Mar 23.
Life-threatening diarrhoea is observed in up to 25% of cancer patients receiving irinotecan. The associations between the UGT1A128 polymorphism and irinotecan-induced diarrhoea remains controversial because of conflicting data in the literature. Meta-analyses were performed on published data in terms of relationships between UGT1A128 and severe diarrhoea. We searched databases for relevant studies that were published in English or Chinese. Two reviewers extracted data and assessed methodological quality. UGT1A128 related odds ratios (ORs) were pooled by use of a fixed-effects model. The studies included were stratified into subgroups representing different races and irinotecan doses, and meta-regression analyses were performed to investigate the effect of study characteristics on the association between UGT1A128 and diarrhoea. Twenty trials including a total of 1760 cancer patients were included. The risk of severe diarrhoea at medium and high irinotecan doses was higher among patients with a UGT1A128/28 genotype than among those with a UGT1A11/1 genotype (OR=3.69, 95% confidence interval [CI]=2.00-6.83; P<0.001). Considering the patients with a UGT1A11/28 genotype, the risk of toxicity was also higher than among those with a wild-type genotype at medium and high doses (OR=1.92, 95% CI=1.31-2.82; P=0.001). No association was observed between UGT1A128 and severe diarrhoea at low doses (<125 mg/m(2)). In conclusion, patients carrying UGT1A128 allele(s) are at an increased risk of irinotecan-induced severe diarrhoea. This increased risk is only apparent in those who are administrated with medium or high irinotecan doses.
在接受伊立替康治疗的癌症患者中，高达 25%的患者会出现危及生命的腹泻。由于文献中的数据存在冲突，UGT1A128 多态性与伊立替康诱导的腹泻之间的关联仍存在争议。我们对已发表的相关数据进行了荟萃分析，以评估 UGT1A128 与严重腹泻之间的关系。我们检索了英文和中文数据库中已发表的相关研究。两位评审员提取数据并评估方法学质量。采用固定效应模型对 UGT1A128 相关比值比（OR）进行汇总。研究分为不同种族和伊立替康剂量亚组，进行荟萃回归分析以评估研究特征对 UGT1A128 与腹泻之间关联的影响。纳入了 20 项试验，共包括 1760 例癌症患者。中高剂量伊立替康治疗时，UGT1A128/28 基因型患者发生严重腹泻的风险高于 UGT1A11/1 基因型患者（OR=3.69，95%CI=2.00-6.83；P<0.001）。考虑到 UGT1A11/28 基因型患者，中高剂量时其毒性风险也高于野生型患者（OR=1.92，95%CI=1.31-2.82；P=0.001）。低剂量（<125mg/m2）时，UGT1A128 与严重腹泻之间无关联。总之，携带 UGT1A128 等位基因的患者发生伊立替康诱导的严重腹泻风险增加。这种增加的风险仅在接受中高剂量伊立替康治疗的患者中显现。
