Document Type : Original research articles
Authors
1
Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
2
Department of Medical Pharmacology, Faculty of Medicine, Luxor University, Luxor, Egypt
3
Department of Clinical Oncology, Faculty of Medicine, Ain shams University, Cairo, Egypt.
4
Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.
5
Unit of Scientific research, Shefa El Orman Hospital, Luxor, Egypt
6
Department of Medical Pharmacology, Faculty of Medicine, South Valley University, Qena, Egypt.
Abstract
Background: 5-Fluorouracil (5-FU) is a cornerstone of advanced colorectal cancer (CRC) treatment. Pharmacogenomics variations in DNA may explain why 5-FU is safe for certain people while negatively affecting others. Examination of dihydropyrimidine dehydrogenase (DPYD) allelic variations would aid in improving dose adjustment. The impact of vitamin D on survival has led to the hypothesis that it lowers cancer mortality.
Objectives: This work aimed to assess the correlation between 5-FU response and toxicities and their association with DPYD genetic polymorphism and vitamin D levels in CRC patients.
Patients and method: A prospective cohort study of 60 CRC patients received 5-FU for 6 months. Patient follow-up to detect clinical adverse effects was done. CBC and liver enzymes were measured before and after treatment. A genotyping study using real-time polymerase chain reaction (PCR) to detect the DPYD*2A (IVS14+1G>A) (rs 3918290) variant was performed. Vitamin D (25(OH)D) serum levels were estimated.
Results: There was a significant increase in chest pain, nausea, febrile neutropenia, and bruising among the 5-FU non-responders compared to the responders. The study showed that hemoglobin, WBCs, neutrophils, and platelet counts were significantly higher among 5-FU responders than non-responders. The decrease was higher 6 months post-treatment compared to pre-treatment in responder and non-responder patients. ALT and bilirubin levels were significantly lower among responders than non-responders, the genotyping study indicated the absence of the DPYD*2A variant among the study cases. There was a higher level of vitamin D among 5-FU responders than the non-responders (31.83 ± 4.35, 11.62 ± 4.68 ng/ml) respectively, (p < 0.001).
Conclusion: 5-FU efficacy and toxicity were unrelated to DPYD genetic polymorphisms among the study patients. However, there was a strong correlation between vitamin D 5-FU efficacy.
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