Polymorphisms in TPMT and TYMS may predict severe toxicity in DPYD wild-type patients receiving fluoropyrimidine (FP) chemotherapy for colorectal cancer.

e13018Background: Approx 20% of patients receiving FP chemotherapy experience grade 3-5 toxicity. Known deleterious DPYD mutations account for 20% of these toxicities. We set out to examine whether polymorphisms/mutations in additional candidate genes involved in FP metabolism might account for severe toxicity in DPYD wild type (WT) individuals Methods: All patients receiving FP chemotherapy in our centre are prospectively screened for 4 common DPYD polymorphisms. Colorectal cancer patients treated between 2012-2015 were eligible if they had previously tested DPYD WT. Patients were identified using an institutional database and medical record review. DPYD WT patients who experienced grade 3/4 toxicity were defined as the case population and those without severe toxicity were categorised as the control population. Following informed consent, buccal swabs were taken to obtain DNA samples in order to genotype candidate genes (TPMT, TYMS and MTHFR). Statistical analysis was carried out on the data set returne...