Folates in the Treatment of Colorectal Cancer

摘要: Folates in the Treatment of Colorectal Cancer Department Surgery Institute Clinical Sciences at Sahlgrenska Academy University Gothenburg Helena Taflin Background: cancer is one most common cancers world, and radical surgery with total removal tumour (RO-resection) single important treatment. However, chemotherapy recommended for patients risk factors metastatic disease. 5-fluoruracil (5-FU) cornerstone chemotherapy, used either as a drug or combination other drugs. 5-FU it almost always combined folate leucovorin (LV). The aim this thesis was to examine role polymorphisms genes involved metabolism relation treatment levels various forms tumours, mucosa, plasma who received LV Modufolin® which biological isomer 5,10methylenetetrahydrofolate. Methods: Polymorphisms methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), thymidylate (TYMS) were analysed using real-time PCR TaqMan chemistry. sensitive liquid chromatography electrospray ionization tandem mass spectrometry technique. Results: There interdependency between MTFHR MTR genes, associated side effects overall survival stage III colorectal receiving adjuvant chemotherapy. Total levels, all well tetrahydrofolate (THF) 5,10-methyleneTHF significantly higher tumours than mucosa tissue. individual variation both greater found when subgrouped by gene polymorphisms. Only half 60 mg/m2 had 0 LV. Patients rectal lower compared colon cancer. THF concentrations (p<0.003, dosages) (p<0.015) 200 mg/m2) after administration (Isovorin®) administration. Conclusions: folate-associated can affect that suffer from during 5-FU-based wide interindividual tissue standardised doses Nordic FLV-treatment may result suboptimal 5,10-methyleneTHF, especially resulted natural l-form LV, Isovorin®, potentially increase efficacy