Department of Clinical Pharmacology, Bispebjerg and Frederiksberg University Hospital, Denmark; Department of Paediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Pharmacology, Bispebjerg and Frederiksberg University Hospital, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark.
Crit Rev Oncol Hematol. 2020 May;149:102939. doi: 10.1016/j.critrevonc.2020.102939. Epub 2020 Apr 4.
A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08-6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT antagonists.
尽管使用了止吐药物,仍有相当一部分癌症患者经历化疗引起的恶心和呕吐(CINV)。参与止吐药物代谢、药物转运和受体途径的常见遗传多态性可能会影响止吐药物的疗效。需要了解将哪些多态性纳入个体化临床治疗中。我们进行了一项系统评价,评估了癌症患者接受中至高度致吐性化疗时,多态性与止吐药物疗效之间的关系。有 20 项研究(n=2331)评估了五个候选基因中与 5-HT 拮抗剂途径相关的 8 个多态性。HTR3C C1214G 在显性模型中增加了急性化疗诱导性呕吐的风险(比值比(OR)=2.67,95%置信区间(CI):1.08-6.63)。ABCB1 C3435T 在隐性模型中降低了急性 CINV 的风险(OR=0.60,95%CI:0.44-0.81)。未来的研究应评估除 5-HT 拮抗剂以外,其他止吐药物的候选基因对药物遗传学的影响。