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Background

Rhabdomyosarcoma (RMS) is a small round blue cell malignant tumor, representing 7% of childhood malignancies, and over 50% of all soft tissue sarcomas. Cyclophosphamide (CPA) is a prodrug and is the mainstay of RMS treatment. CYP2B6 is a highly polymorphic drug metabolizing enzyme involved in CPA bioactivation. The influence of CYP2B6 single nucleotide polymorphisms (SNPs) on the survival of RMS is still unknown.

Methods

We genotyped CYP2B6SNPs rs2279343, rs3745274, and rs3211371 by restriction fragment polymorphism (RFLP) after PCR amplification in a cohort of 73 pediatric RMS patients treated with CPA-based first line treatment. We then analyzed the association between those genotypes and survival outcome of RMS.

Results

The frequencies of CYP2B6 rs2279343, rs3745274, and rs3211371 were 63%, 45.2%, and 5.5%, respectively. There was no association between rs3745274, rs3211371 genotypes and survival outcomes of RMS. However, the carriers of at least one mutant allele CYP2B6rs2279343 had significantly longer event-free survival (p-value = 0.03).

Conclusion

Our results demonstrated that CYP2B6 rs2279343 may predict EFS in RMS patients and warrants future studies to clarify the pharmacogenetics of CPA in pediatrics. If validated, integration of genetic factors with clinical and molecular characteristics could be used for a composite algorithm to better stratify risk prior to treatment."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0158890"xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/author"A Abdelrahim M.E."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/author"Elnadi E."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/author"Hesham R.M."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/author"Labib R.M."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/author"Yassin D."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/pages"e0158890"xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/title"CYP2B6rs2279343 Is Associated with Improved Survival of Pediatric Rhabdomyosarcoma Treated with Cyclophosphamide."xsd:string
http://purl.uniprot.org/citations/27388155http://purl.uniprot.org/core/volume"11"xsd:string
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