Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers

Background. Thymidylate synthase (TS) is a target enzyme of 5-flourouracil (5-FU), and the TS gene has a polymorphic tandem repeated sequence in the 5 '-untranslated region. We investigated the polymorphism on the repeat lengt h of the TS gene and its relation to the number of 5-fluoro-dUMP (FdUMP) bi nding sites in human gastrointestinal cancers. Materials and Methods. Seven ty adenocarcinoma samples were used. Twenty-one patients received UFT(R) an d 49 patients received no treatment before surgery. Tandem repeat length of TS gene was determined by PCR amplification of genomic DNA. (3)The number of FdUMP binding sites were measured by H-3-FdUMP binding assay. Results. D ouble- (2R) and triple-repeated (3R) sequences of the TS gene were found in the cancer tissues. Three genotypes of TS were found: 2R/2R (n = 3), 2R/3R (n = 16) and 3R/3R (n = 51). The free TS level for the 3R/3R genotype was significantly higher than that for the 2R/3R genotype in UFT(R) (+) group. Similar genotype-dependent difference of TS level was observed in UFT(R) (- ) group. Conclusions. Our results suggest the link between TS genotype and TS protein expression. This link might offer an advantage for selection of patients to receive 5-FU-based chemotherapy.