5-fluorouracil (5FU) is a potent antimetabolite that is the currently accepted adjuvant treatment for colorectal cancer. As well, 5FU is used to treat head and neck cancers, breast cancer and gastric cancer. In 1985, Takeishi et al demonstrated that thymidylate synthase's gene had a satellite in the 5' untranslated region, which consisted of 3 tandem repeats of a 28 base pair sequence. Horie et al demonstrated that these satellites were polymorphic in length due to different numbers of tandem repeats, with 2 length polymorphism existing 2 tandem repeats of 28 base pairs (2R) and 3 tandem repeats of 28 base pairs (3R). Subsequent authors have demonstrated 4 repeats (4R), five repeats (5R) and nine repeats (9R). Kawakami et al demonstrated that the number of tandem repeats affected TS gene translation. They showed those patients homozygous for 3R alleles had higher TS protein levels than 2R/3R heterozygotes. Using in vitro expression of 2R and 3R genes they demonstrated that the increased protein levels were due to increased translational efficiency of the 3R RNA and not due to increased 3R mRNA expression. These tandem repeats are predictive of response rates of various cancers to fluoropyrimidine cancer chemotherapy. Park et al showed in metastatic colorectal cancer patients treated with capecitabine, the response rate was 14% in patients homozygous for 3R repeats, and 80% in the patients homozygous for 2R repeats. No prospective study has examined if a patient's TS genotype predicts for 5-FU toxicity.