Relationship Between Dihydropyrimidine Dehydrogenase Gene Polymorphism and Toxicities in Cancer Patients Receiving 5-Fluorouracil

Abstract

Objective: Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme that degrades uracil, thymine, and 5-fluorouracil, which are important for treating gastric, colorectal, and breast cancers. In this study, we aimed to determine the association between chemotherapy-related toxicities and DPD gene variants; evaluate the consequences of these genetic differences; and integrate DPYD genetic screening into conventional cancer treatment regimens. Methods: Sixty-two patient files from 2015 to 2018 were retrospectively reviewed to investigate whether the DPYD gene causes toxicity before or during treatment. A total of 50 patients were enrolled after receiving informed consent and ethical clearance for the comprehensive examinations. The aim of this study was to reveal the genetic causes of adverse effects and better understand treatment responses. Results: Our analysis of 50 patients with cancer revealed that the severity of response to fluoropyrimidine compounds used in chemotherapy varied depending on DPYD gene polymorphisms. These mutations increased susceptibility to severe neutropenia -which can weaken immune systems- among other negative effects. It also found that IVS14 + 1G>A had a significant effect on treatment outcome, indicating that genetic screening should be included in planning therapy as it can prevent major side effects. Conclusion: Dihydropyrimidine connected to dehydrogenase gene polymorphism occurred in patients with gastrointestinal cancer who developed diarrhea, nausea, anemia, thrombostitopenia, and grade 3-4 neutropenia side effects while receiving 5-FU.

Keywords

• dihydropyrimidine dehydrogenase
• 5-fluorouracil
• gene polymorphism