Please use this identifier to cite or link to this item: https://scholarhub.balamand.edu.lb/handle/uob/6026
Title: Association of CYP3A4/5 genotypes and expression with the survival of patients with neuroblastoma
Authors: Darwish, Mohamad H
Farah, Roula A
Farhat, Ghada N
Torbey, Paul-Henri N
Ghandour, Fatima A
Bejjani-Doueihy, Noha A
Dhaini, Hassan R
Affiliations: Faculty of Health Sciences 
Keywords: CYP3A4
CYP3A5
Cytochrome P450
Lebanese
Neuroblastoma
Survival
Issue Date: 2015
Part of: Molecular Medicine Reports
Volume: 11
Issue: 2
Start page: 1462
End page: 1468
Abstract: 
Neuroblastoma (NB) is a rare pediatric disease in Lebanon for which poor prognosis remains a major challenge. Genetic polymorphism of genes coding for drug‑metabolizing enzymes may influence the response of a patient to chemotherapy. This study investigates a possible association between CYP3A4/5 polymorphism and expression levels and survival in NB patients. All patients with stage III and IV NB diagnosed between 1993 and 2012 in three major hospitals in Beirut were included (n=27). Demographic information and survival time were obtained from medical records. CYP3A4 and CYP3A5 genotypes and expression levels were determined in archival tumors by polymerase chain reaction (PCR) and restriction fragment length polymorphism and quantitative PCR, respectively. Additionally, MYCN amplification was assessed. A Cox proportional hazards model was used to evaluate potential associations, adjusting for MYCN amplification. A statistically significant increase in the risk of mortality was observed in patients with MYCN amplification [hazard ratio (HR) 4.11, 95% confidence interval (CI) 1.14‑14.80]. Patients with CYP3A5 expression levels above the median had a lower risk of mortality (HR 0.61, 95% CI 0.21‑1.74) and patients with CYP3A4 expression levels above the median had a higher risk of mortality (HR 2.00, 95% CI 0.67‑5.90). CYP3A5*3/*3 homozygote mutants had a 4.3‑fold increase in the risk of mortality compared with that of homozygote wild‑type or heterozygote mutants (HR 4.30, 95% CI 0.56‑33.30). Carriers of the CYP3A4*1B mutant allele had a 52% lower risk of mortality compared with that of non‑carriers (HR 0.48, 95% CI 0.06‑3.76). Although the results of the present study did not achieve statistical significance, associations were observed, which indicates that CYP3A4 and CYP3A5 may modulate the clinical outcome of NB. Further studies with larger sample sizes are required to characterize the effects of the polymorphism and expression levels of CYP3A4/5 on the survival of patients with NB.
URI: https://scholarhub.balamand.edu.lb/handle/uob/6026
ISSN: 17912997
DOI: 10.3892/mmr.2014.2835
Ezproxy URL: Link to full text
Type: Journal Article
Appears in Collections:Nursing Program

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