A Single Nucleotide Polymorphism (SNP) in the
Adult
Aged
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Male
Melphalan
/ adverse effects
Middle Aged
Multiple Myeloma
/ complications
Organic Cation Transport Proteins
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Stem Cell Transplantation
/ adverse effects
Stomatitis
/ epidemiology
Transplantation, Autologous
/ adverse effects
Multiple myeloma
OCT3
SLC22A3
melphalan
oral mucositis
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
28
10
2021
revised:
16
11
2021
accepted:
22
11
2021
entrez:
31
12
2021
pubmed:
1
1
2022
medline:
13
1
2022
Statut:
ppublish
Résumé
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. Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/ΜS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays. 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). OCT3 might be involved in melphalan transport in MM patients.
Sections du résumé
BACKGROUND
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
METHODS
Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/ΜS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays.
RESULTS
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
CONCLUSIONS
OCT3 might be involved in melphalan transport in MM patients.
Identifiants
pubmed: 34969749
pii: 42/1/385
doi: 10.21873/anticanres.15497
doi:
Substances chimiques
Organic Cation Transport Proteins
0
solute carrier family 22 (organic cation transporter), member 3
0
Melphalan
Q41OR9510P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
385-395Informations de copyright
Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.