Thymidylate synthase (TS) gene polymorphisms affect disease free- (DFS) and overall (OS) survival of colorectal cancer (CRC) patients treated with adjuvant 5-fluorouracil-folinic acid (FUFA)

3581 Background: TS, the target enzym of 5-FU has a 28 bp polymorphism in the promoter region containing commonly double of triple tandem repeats of a 28 bp sequence (2R or 3R), and a 6bp ins/del polymorphism on the 3'UTR. Our aim was to study the influence of these TS polymorphisms on tumor response to adjuvant FUFA therapy in CRC patients. Methods: : 89 CRC patients receiving adjuvant FUFA were involved in the study. FUFA was given as bolus (Mayo regimen) or continuous infusion (de Gramont protocoll). TS polymorphisms were determined by PCR PAGE and RFLP method. Results: DFS was significantly longer (p=0,036 logrank test) in patients with +6/+6,+6/-6 genotypes than in –6/-6 genotype.OS was significantly longer (p=0,025) in 3/3 genotype than in 2/3and 2/2 genotype. In rectal cancer +/+ and +/- 3'UTR patients had longer OS than -/- patients (p=0,007).No significant correlation between gene polymorphisms, age, gender, and localization were found. Conclusions: Both TS polymorphisms studied do affect the cli...