Division of Oncology, AO Spedali Civili, University of Brescia Medical School, Brescia, Italy.
Pharmacology. 2012;89(1-2):99-102. doi: 10.1159/000335784. Epub 2012 Feb 15.
Personalized medicine is becoming an important tool in oncology, both in preventing disease and in optimizing the treatment of existing cancers. Here we describe the cases of 2 patients with relevant systemic toxicity following 5-fluorouracil (5-FU) therapy and we study the more frequent polymorphisms in the target genes, in particular: (1) the variability in the number of 28-base repetitions present in the 5'-untranslated sequence of the thymidine synthase gene; (2) the presence of single-nucleotide polymorphisms in the methylene tetrahydrofolate reductase gene, and (3) the presence of mRNA splicing in intron 14 of the hepatic enzyme dihydropyrimidine dehydrogenase. The 5-FU gene profile of our patients strongly suggested that the polymorphisms expressed may contribute to the adverse effects seen during the therapy. To what extent these polymorphisms induced adverse effects cannot be established at present; however, our results strengthen the relevance of the 5-FU-related pharmacogenomic profile to predict the response outcome and the chemotherapy toxicity.
个体化医学正在成为肿瘤学中的一个重要工具，无论是在预防疾病还是优化现有癌症的治疗方面。在这里，我们描述了 2 例患者在接受氟尿嘧啶（5-FU）治疗后出现相关全身毒性的病例，并研究了靶基因中更常见的多态性，特别是：（1）胸苷酸合成酶基因 5'-非翻译序列中存在的 28 个碱基重复数的变异性；（2）亚甲基四氢叶酸还原酶基因中的单核苷酸多态性；（3）二氢嘧啶脱氢酶基因内含子 14 中的 mRNA 剪接。我们患者的 5-FU 基因谱强烈表明，表达的多态性可能有助于治疗期间出现的不良反应。目前尚不能确定这些多态性在多大程度上引起不良反应；然而，我们的结果加强了与 5-FU 相关的药物基因组学特征在预测反应结果和化疗毒性方面的相关性。
