Role of dihydropyrimidine dehydrogenase genetic polymorphism and vitamin D assay for 5-Fluorouracil therapy in Upper Egypt colorectal cancer patients | ||||
| SVU-International Journal of Medical Sciences | ||||
| Article 80, Volume 7, Issue 2, July 2024, Page 917-935 PDF (617.03 K) | ||||
| Document Type: Original research articles | ||||
| DOI: 10.21608/svuijm.2024.308049.1949 | ||||
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| Authors | ||||
Mohamed M. Elbadr1; Mirna M. Mahrous  2; Mohamed Alorabi3; Hala M. Elbadre4; Rehab Mohamed5; Reham A.M. Ellisy6
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| 1Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. | ||||
| 2Department of Medical Pharmacology, Faculty of Medicine, Luxor University, Luxor, Egypt | ||||
| 3Department of Clinical Oncology, Faculty of Medicine, Ain shams University, Cairo, Egypt. | ||||
| 4Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt. | ||||
| 5Unit of Scientific research, Shefa El Orman Hospital, Luxor, Egypt | ||||
| 6Department 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. | ||||
| Keywords | ||||
| Colorectal cancer; Dihydropyrimidine dehydrogenase; 5-fluorouracil; Genetic polymorphism; vitamin D | ||||
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