期刊
JOURNAL OF PERSONALIZED MEDICINE
卷 12, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/jpm12020225
关键词
fluoropyrimidine; dihydropyrimidine dehydrogenase; DPYD; toxicity; meta-analysis
资金
- Medical Research Center Program of the National Research Foundation - Korean government (Ministry of Science, ICT & Future Planning) [2017R1A5A2015541]
- Development Fund Foundation
- Gyeongsang National University
This study aimed to evaluate the risk of fluoropyrimidine-associated toxicity in patients with DPYD rs1801160 polymorphism. The systematic literature review and meta-analysis revealed an association between rs1801160 polymorphism and fluoropyrimidine-associated toxicity.
Background: Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase (DPYD) gene encodes DPD, and studies suggest that DPYD polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with DPYD rs1801160 polymorphism. Methods: We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity. Results: The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83). Conclusions: rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. Therefore, rs1801160 can be a potential candidate for DPD deficiency screening prior to fluoropyrimidine-based regimen.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据