Introduction: Several studies have shown an association between 5-fluorouracil toxicity and variations in the dihydropyrimidine dehydrogenase (DPYD) gene.
Objectives: This cross-sectional study aims to elucidate the association between genetic variations in the DPYD gene and 5-fluorouracil toxicity among Jordanians with colorectal cancer (CRC).
Methods: 80 CRC Patients were recruited to screen for mutations in the DPYD gene using the Sanger sequencing technique. Sequencing results were analyzed using Mutation Surveyor software, and mutational effects were predicted by the Mutation Tester bioinformatics tool.
Results: Three reported variants (c.85T>C, c.1740+40A>G, c.1740+39C>T) and one novel (g.97515583_97515584insA) variant were identified in this study. Results showed a significant association between these variants and toxicity to 5-Fluorouracil with P-values 0.002, 0.005, 0.019, 0.017, respectively. However, there was no significant association between variants and cancer free survival.
Conclusion: The present study identified several variants in the DPYD gene among Jordanians with colorectal cancer, which are associated with toxicity to 5-Fluorouracil treatment.
Keywords: 5-fluorouracil; DPYD; colorectal cancer; pharmacogenetics.