Abstract 509P
Background
Pharmacogenomics (PG) studies show that differences in human genes may explain why some drugs work safely in some patients but can cause side effects in others. These phenomena may have potential influence on drug-dosing regimen and affects final outcomes. The toxicity of anticancer therapies is common amongst gastrointestinal cancer (GI)-treated patients. It can be better adapted if PG testing is performed before initiation of chemotherapy. For example, the analysis of dihydro-pyrimidine dehydrogenase (DPYD) allelic variants for the administration of fluoropyrimidines would help to adjust better the drug dosage. The main objective of this study was to determine the incidence of five main DPYD-gene variants in GI cancer patients.
Methods
The patients with GI cancers, initially selected for treatment with fluoropyrimidines were included to this study. Before a treatment, a genotype of main DPYD pathological variants: rs3918290, rs55886062, rs56038477, rs67376798, rs75017182 was examined. These variants were analyzed in peripheral blood test by RT-PCR reactions for each independent variant by the central lab. There were no procedures for patient selection other than planned treatment with fluoropyrimidines. The incidence of these genotype variants was collected and compared with historical control.
Results
This cohort involved 3215 patients. The overall incidence of defined DPYD mutations was found as 2.4%. The rs56038477 variant had the highest prevalence (1.5%), followed by rs3918290 (0.68%) and rs67376798 (0.22%). No variant was detected so far for rs55886062. In contemporary with recent reports, we found a total linkage disequilibrium of variants rs56038477 and rs75017182 in all cases detected.
Conclusions
The data suggests that germline PG testing for five variants of the DPYD gene could help to identify a substantial proportion of patients who may have a high risk to develop adverse effects of chemotherapy. We conclude that it is important to validate data in different populations. The information of DPYD variants incidence may potentially contribute to more precise medical decision. The data of our study may be compared with different genome-populations, therefore future international studies should be warranted.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.