Journal
ANTICANCER RESEARCH
Volume 42, Issue 1, Pages 385-395Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.15497
Keywords
Multiple myeloma; melphalan; OCT3; oral mucositis
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Funding
- Pelotonia IDEA award [46050-502048]
- College of Pharmacy, The Ohio State University
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This study investigated the association of select single nucleotide polymorphisms in the SLC22A3 gene with clinical outcomes in multiple myeloma patients. The results suggested that a specific genotype was associated with altered melphalan transport and an increased risk of severe oral mucositis.
Background: It has been reported that expression of OCT3 enhanced the sensitivity to melphalan in cells, indicative of potential roles of OCT3 in melphalan transport. Herein we investigated the association of select single nucleotide polymorphisms in SLC22A3 (gene encoding OCT3) with clinical outcomes in multiple myeloma (MM) patients with hematopoietic autologous stem cell transplants followed by high-dose melphalan therapy. Materials and Methods: Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays. Results: Rs3088442 A variant carriers had a significantly increased risk of severe oral mucositis in comparison with homozygous rs3088442 G carriers with adjusted odds ratio of 4.00 (95% CI=1.25-14.7; p=0.027). Rs3088442 A carriers tended to have lower creatinine clearance (p=0.10) and higher maximum plasma concentration of melphalan (p=0.07). Conclusion: OCT3 might be involved in melphalan transport in MM patients.
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