Marcuello E, Altés A, Menoyo A, Rio E Del, Baiget M
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Avda. S. Antoni M. Claret 167, 08025, Barcelona, Spain.
Cancer Chemother Pharmacol. 2006 Jun;57(6):835-40. doi: 10.1007/s00280-005-0089-1. Epub 2005 Sep 27.
Fluorouracil (5-FU) is widely used in the treatment of colorectal cancer. Methylenetetrahydrofolate reductase (MTHFR) may play a central role in the action of 5-FU, an inhibitor of thymidylate synthase, by converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The aim of this study was to ascertain whether two polymorphisms in the MTHFR gene (677C>T and 1298 A>C) could be used as genomic predictors of clinical response to fluoropyrimidine-based chemotherapy (in combination with irinotecan or oxaliplatin). Ninety-four patients diagnosed with metastatic colorectal cancer and undergoing 5-FU-containing chemotherapy as a first line treatment were studied. The results suggest that the MTHFR genotype cannot be considered as an independent factor of outcome in colorectal cancer patients under 5-FU-based chemotherapy.
氟尿嘧啶(5-FU)广泛应用于结直肠癌的治疗。亚甲基四氢叶酸还原酶(MTHFR)可能在胸苷酸合成酶抑制剂5-FU的作用中发挥核心作用,它可将5,10-亚甲基四氢叶酸转化为5-甲基四氢叶酸。本研究的目的是确定MTHFR基因中的两个多态性(677C>T和1298 A>C)是否可作为基于氟嘧啶的化疗(联合伊立替康或奥沙利铂)临床反应的基因组预测指标。对94例诊断为转移性结直肠癌并接受含5-FU化疗作为一线治疗的患者进行了研究。结果表明,在接受基于5-FU化疗的结直肠癌患者中,MTHFR基因型不能被视为预后的独立因素。