Evaluation of side effects of chemotherapyregimens containing ۵-fluoropyrimidines derivativesand the effect of DPYD polymorphisms on adverse drug reactionin colorectal cancer patients

Background: One of the most common types of cancers in theworld is colorectal cancer (CRC). Fluoropyrimidine derivativessuch as ۵-Fluorouracil (۵-FU) and Capecitabine are some ofthe most common medications in chemotherapy of CRC. Dihydropyrimidinedehydrogenase enzyme (DPYD) is the main metabolizingenzyme for these drugs. The genetic polymorphismencoding this enzyme, may reduce or eliminate the activity ofthe enzyme, leading to accumulation of drugs and their metabolitesand potential toxicity. In this study, the prevalence of somecommon DPYD polymorphisms and the association betweenside effects of fluoropyrimidine derivatives with DPYD polymorphismin CRC patients was discussed.Materials and Methods: In this cross-sectional study, ۸۸ CRCpatients from Imam Khomeini hospital in Sari city center ofMazandaran province were considered. Initially, ۲ ml of peripheralblood was collected from each patient, and then thepolymorphisms of DPYD gene such as IVS ۱۴+۱ G>A, ۲۸۴۶A>T and ۲۱۹۴ G>A mutant were detected by DNA extraction,polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method.Results: By analysis of ۲۲۷ chemotherapy cycle of ۸۸ CRCpatients, prevalence of IVS۱۴+۱ G>A mutant was ۵/۵%, whilenone of the patients showed ۲۸۴۶ A>T and ۲۱۹۴ G>A mutant.patients with IVS۱۴+۱ G>A polymorphism had higher adversedrug reactions(ADRs) rather than normal patients. The prevalenceof chemotherapy-induced diarrhea, nausea, vomiting andoral mucositis between FOLFOX and FOLFIRI regimens wasnot significant. Although, peripheral neuropathy with FOLFOXregimen (P < ۰.۰۰۱) and hair loss in FOLFIRI regimen (P =۰.۰۴۸) were significant.Conclusion: ADRs in CRC patients could be related to typeof regimen (FOLFOX and FOLFIRI) and polymorphism of themetabolizing enzyme.

کلیدواژه ها:

Colorectal cancer ، ۵-fluorouracil ، Polymorphism ، Dihydropyrimidinedehydrogenase ، Adverse drug reaction