Page 48 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 3
proposed by Gaedigk et al. has proven beneficial for CYP2D6, for which a large number of polymorphisms are known.
Figure 1. DHU/U ratio according to DPYD genotype
Shown are individual values and a box plot with the median of the DHU/U ratio for patients with a DPYD polymorphism or DPYD wild-type patients.
Abbreviations: DHU: Dihydrouracil, U: Uracil
We have fully investigated and described four SNPs in DPYD (DPYD*2A, c.2846A>T, DPYD*13, c.1236G>A/HapB3). This literature review describes what DPD enzyme activities are to be expected in patients with a certain SNP in DPYD. In addition to that, we have shown additional data of pretreatment DHU/U ratio in correlation to DPYD*2A, c.2846A>T, DPYD*13 and c.1236G>A. We focus on these four SNPs because, based on the available literature data, we believe they are the most relevant. Additional SNPs can be easily added to the gene activity score in the future when sufficient data are available. An outline for the suggested assigned values to various alleles of DPYD is given in Table 1. So far only the four SNPs described above are included, because sufficient evidence is available that they result in low DPD enzyme activity and severe fluoropyrimidine-related toxicity. Consequently, following the calculated gene activity scores for DPYD an individualized dose recommendation for fluoropyrimidines can be given, as is shown in Table 2. This is a recommendation for a starting dose; after the
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