Molecular diagnostics for pharmacogenomic testing of fluoropyrimidine based-therapy: costs, methods and applications

Genetic testing of drug response represents an important goal for targeted therapy. In particular, 5-fluorouracil (5-FU) is the backbone of several chemotherapic protocols for treatment of solid tumors. Unfortunately, in some patients, 5-FU is toxic and causes gastrointestinal and hematologic lesions leading to the suspension of therapy. Some adverse drug responses can be predicted by pharmacogenomics. Recently, several polymorphic traits of different genes involved with 5-FU biotransformation have been reported. Many methods have been used for qualitative and quantitative assessment of the mutational status of these genes, without a precise cost-effectiveness analysis. This article reviews recent findings on the seven germline polymorphic traits of four genes involved in the biotransformation of the 5-FU. In particular, we analyze the most common platforms used to identify the specific genetic alterations and their relative costs. Genotyping can be performed either by custom service laboratories or academic reference laboratories by using either the commercial kits (when available) or “in house” tests. By random selection of 20 certified laboratories out of a total of 71, we estimate that the cost of the analysis/single trait is on average €120.00 as custom genotyping service. “In house” validated tests by PCR-based platforms cost approximately €20.00 per single polimorphism. On the basis of this information, the lab manager can evaluate the advantage and limitations, in terms of costs and applicability, of the most appropriate methods for diagnostics of 5-FU pharmacogenomics tests.