Predictive diagnostics in colorectal cancer: Impact of genetic polymorphisms on individual outcomes and treatment with fluoropyrimidine-based chemotherapy

Abstract

The 5-fluorouracil (5-FU)-based chemotherapy is a standard treatment for patients with colorectal cancer. However, a relevant number of patients suffer from severe toxic side effects, such as haemotoxicity, while lacking clinical response to adjuvant therapy. The inter-individual variations of drug toxicity and efficacy of the pyrimidine antagonist observed in clinical practice are mainly determined by genetic polymorphisms. The screening of genotypes, such as thymidylate synthase, dihydropyrimidine dehydrogenase, methylene tetrahydrofolate reductase, orotate phosphoribosyltransferase or glutathione S-transferase, could help identifying those patients with colorectal carcinoma who can actually benefit from a 5-FU-based therapy. The current chapter elucidates the roles of the polymorphisms in the enzymes involved in the 5-FU metabolic pathway as prognostic and predictive markers. It reports on the relationship between various genotypes in patients with colorectal carcinoma and their responsiveness to a 5-FU-based chemotherapy, and concludes with an outlook on possible future directions in treatment of colorectal cancer. © 2010 European Association for Predictive, Preventive and Personalised Medicine.