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In cancer patients receiving fluoropyrimidine-based chemo-therapy, there is extensive inter-individual variability in plasma drug concentrations and the severity of chemo-therapy-related toxicity. A strong association has been shown for plasma concentrations and drug-related toxicity as well as clinical outcome in 5-fluorouracil treated cancer patients. In spite of the identification of some genetic risk factors that contribute to this inter-individual variability, a majority of toxicity occurrences remain unexplained. Cur-rently, variability in drug exposure related to BSA-based dosing hampers the identification of genetic factors con-tributing to individual FP toxicity risk and the quantification of their clinical relevance. Thus, the power of association studies can be improved by accounting for differences in individual drug exposure.