单核苷酸多态性对消化道恶性肿瘤化疗药物反应和毒性的影响

Correlation between the Single-nucleotide Polymorphism and the Curative Effect/Side Effect of Chemotherapy for Malignant Gastrointestinal Tumor

长期以来绝大多数化疗药物的疗效在不同个体间的差异受到临床医生的高度关注,其药物反应和毒性不仅与患者的年龄、性别以及药物间相互作用等因素有关,而且和参与药物代谢的蛋白或酶的表达水平有关。单核苷酸多态性是基因组中最常见的一种遗传变异,为了揭示个体之间因基因学的差异导致的化疗药物反应以及毒副作用的差异性,近年来对单核苷酸多态性与化疗药物反应及毒性之间相关性的研究和报道逐渐增多。但对各种单核苷酸多态性能否作为化疗药物反应及毒副作用的预测指标未得出统一定论。本文以消化道恶性肿瘤常用化疗药物为例,分别对5-氟尿嘧啶(5-FU)类、铂类、紫杉类和伊立替康相关的单核苷酸多态性(SNP)进行综述。

For a long time, clinicians have been paying increasing attention to the differences in the efficacy of anticancer drugs among various patients. The curative effects and possible side effects of chemotherapy are not only related to factors such as age, gender, and drug interactions but also to the expression of the proteins or enzymes involved in the metabolism of chemotherapeutic drugs. Single-nucleotide polymorphism is the most common form of genetic variation. Studies on the correlation between single-nucleotide polymorphism and the effects or side effects of chemotherapy have been increasingly conducted to investigate the differences in the therapeutic effects and side effects of drugs, which are caused by the genetic variations among individuals. However, single-nucleotide polymorphism has not been ascertained as a predictor of the effects and side effects of chemotherapy. The current study reviewed the single-nucleotide polymorphism correlated with fluorouracil, platinum, paclitaxel, and irinotecan, taking chemotherapeutic drugs for malignant gastrointestinal tumor as the example.