Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
J Hum Genet. 2019 Dec;64(12):1195-1202. doi: 10.1038/s10038-019-0677-2. Epub 2019 Oct 4.
It has been reported that there are differences in effects on irinotecan-induced adverse reactions between UGT1A16 and UGT1A128. In order to compare those differences in the Japanese population, we examined the associations between UGT1A1 and irinotecan-induced adverse reactions using the BioBank Japan Project database. We genotyped UTG1A16 and UGT1A128 and conducted case-control analyses. A total of 651 patients (102 cases and 549 tolerant controls) were included in this study. The results showed that UGT1A16/6 is a predictor of adverse drug reactions (ADRs) (p-value 0.00070, odds ratio 6.59, 95% confidence interval 2.33-18.6), whereas UGT1A16/28 and UGT1A128/28 were not. The subanalysis comprising only patients with UGT1A16/6, UGT1A16/28, and UGT1A128/28 revealed a trend towards an increased risk of ADRs in patients with UGT1A16 (p-value 0.0092, odds ratio 4.39, 95% confidence interval 1.57-14.9). Multiple logistic regression analyses showed that use of platinum-based antineoplastic drugs and presence of UGT1A16/6 were independent variables, significantly associated with ADRs. The diagnostic performance of a predictive model had a sensitivity of 49.0%, specificity of 70.1%, and a number needed to screen of 5.8. We concluded that UGT1A1 testing could be useful to predict irinotecan-induced ADRs, and that UTG1A16 rather than UGT1A1*28 contributed to ADR occurrence.
据报道，UGT1A16 和 UGT1A128 对伊立替康诱导的不良反应的影响存在差异。为了比较日本人群中的这些差异，我们使用 BioBank Japan 项目数据库检查了 UGT1A1 与伊立替康诱导的不良反应之间的关联。我们对 UGT1A16 和 UGT1A128 进行了基因分型，并进行了病例对照分析。本研究共纳入 651 例患者（102 例病例和 549 例耐受对照）。结果表明，UGT1A16/6 是药物不良反应（ADR）的预测因子（p 值 0.00070，优势比 6.59，95%置信区间 2.33-18.6），而 UGT1A16/28 和 UGT1A128/28 则不是。仅包含 UGT1A16/6、UGT1A16/28 和 UGT1A128/28 的亚组分析显示，UGT1A16 患者的 ADR 风险有增加趋势（p 值 0.0092，优势比 4.39，95%置信区间 1.57-14.9）。多元逻辑回归分析表明，使用铂类抗肿瘤药物和 UGT1A16/6 是与 ADR 显著相关的独立变量。预测模型的诊断性能具有 49.0%的敏感性、70.1%的特异性和 5.8 的筛查数量。我们得出结论，UGT1A1 检测可用于预测伊立替康诱导的 ADR，而 UGT1A16 而不是 UGT1A1*28 导致 ADR 发生。
