Recently, the thymidylate synthase gene's promoter has been found to be polymorphic, with variable numbers of tandem repeats of 28 base pairs in length. These polymorphisms have been associated with tumor response to treatment with fluoropyrimidines. The researchers hypothesize that polymorphisms in thymidylate synthase (TS) gene's promoter region are associated with toxicity from 5-fluorouracil (5FU)/leucovorin (LV) treatment specifically development of myelosuppression and diarrhea. The researchers hypothesize that a polymorphism in methylene tetrahydrofolate reductase (MTHFR) is also associated with toxicity and efficacy of 5FU/LV treatment. The researchers speculate that the MTHFR polymorphism only becomes clinically significant by stratifying patients by TS promoter polymorphisms.