Jakobsen Anders, Nielsen Jens Nederby, Gyldenkerne Niels, Lindeberg Jan
Danish Colorectal Cancer, Group South, Vejle Hospital, 7100 Vejle, Denmark.
J Clin Oncol. 2005 Mar 1;23(7):1365-9. doi: 10.1200/JCO.2005.06.219.
To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes.
The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial.
The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.
分析胸苷酸合成酶（TS）和亚甲基四氢叶酸还原酶（MTHFR）基因多态性与氟尿嘧啶（FU）敏感性的关系。
本研究包括对88例转移性结直肠癌患者的回顾性分析以及对51例同样有可测量转移灶患者的前瞻性试验。所有患者均接受FU和亚叶酸治疗。基因多态性分析在正常肠组织和淋巴细胞上进行。
与其他组相比，TS 3R/3R或MTHFR 677 TT基因多态性患者的缓解率显著更高。缓解率的差异转化为疾病进展时间的差异。在回顾性分析和前瞻性验证试验中观察到了相似的结果。
基因多态性分析能够确定一组患者（30%），其对单一药物的缓解率约为50%。该信息应用于个体化治疗方案的设计。
