Chemotherapeutic agents 5-fluorouracil (5-FU) (Adrucil®; SP Pharmaceuticals) and capecitabine (Xeloda®; Roche Laboratories Inc.) are used for the treatment of a range of tumors, including those in the colon (both agents), rectum (5-FU), breast (both agents), stomach (5-FU), and pancreas (5-FU). Toxicity, including hand-foot syndrome, diarrhea, stomatitis, neutropenia, and neurotoxicity, has been reported with both agents. Capecitabine is a synthetic precursor of 5-FU, which was developed to provide a less toxic alternative to 5-FU. The primary mechanism of 5-FU is inhibition of thymidylate synthase. The thymidylate synthase gene (TYMS) is located at chromosome 18 at band p11.32. In vivo enzymatic catabolism of 5-FU is performed by dihydropyrimidine dehydrogenase, whose gene DPYD is located at chromosome 1 at band p22. Functional variants in TYMS and DPYD are implicated in 5-FU/capecitabine-based treatment toxicity. The TheraGuide 5-FU test analyzes the entire coding region of DPYD for clinically significant sequence variants, as
well as a specific variant (c.-97_-70(2_3)) located in the 5’ untranslated region (UTR) of the TYMS gene.