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Polymorphisms of the glucocorticoid receptor gene: impact on clinical outcome of multiple myeloma

Polymorphisms of the glucocorticoid receptor gene: impact on clinical outcome of multiple myeloma The genetic abnormalities that contribute to the etiology and prognosis of multiple myeloma (MM) are not fully understood. Polymorphisms of various genes encoding drug transporters and drug targets are potential factors that can influence the risk of developing MM as well as outcome of chemotherapy. NR3C1 gene encodes glucocorticoid receptors which are the cellular target of dexamethasone, the most active component of the VAD scheme used in MM patient treatment. The aim of this study is to look into the influence of investigated polymorphisms on the predisposition to MM development and the efficacy of glucocorticoid-including therapy. The frequencies of functional polymorphisms N363S and BclI of NR3C1 gene were evaluated using PCR-RFLP in 96 MM patients and 55 control subjects. Associations between the presence of particular NR3C1 genotypes and alleles and MM prevalence as well as prognostic factors, such as WHO classification, creatinine levels, and the Durie–Salmon staging system, were evaluated. The G allele for BclI and the A allele for N363S were found to be significantly linked with an increased risk of MM (p = 0.0281 and 0.0000, respectively). There were no associations between genotype/allele frequencies and prognostic factors except the presence of allele G for BclI and higher level of CRP (p = 0.0435). Statistical analysis did not show any connections between the presence of particular genotype for BclI and overall survival time of MM patients. The investigated polymorphisms of the NR3C1 gene have major influences on MM development risk. However, BclI does not affect the response to VAD therapy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Comparative Clinical Pathology Springer Journals

Polymorphisms of the glucocorticoid receptor gene: impact on clinical outcome of multiple myeloma

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References (26)

Publisher
Springer Journals
Copyright
Copyright © 2011 by Springer-Verlag London Limited
Subject
Medicine & Public Health; Pathology; Hematology; Oncology
eISSN
1618-565X
DOI
10.1007/s00580-011-1379-0
Publisher site
See Article on Publisher Site

Abstract

The genetic abnormalities that contribute to the etiology and prognosis of multiple myeloma (MM) are not fully understood. Polymorphisms of various genes encoding drug transporters and drug targets are potential factors that can influence the risk of developing MM as well as outcome of chemotherapy. NR3C1 gene encodes glucocorticoid receptors which are the cellular target of dexamethasone, the most active component of the VAD scheme used in MM patient treatment. The aim of this study is to look into the influence of investigated polymorphisms on the predisposition to MM development and the efficacy of glucocorticoid-including therapy. The frequencies of functional polymorphisms N363S and BclI of NR3C1 gene were evaluated using PCR-RFLP in 96 MM patients and 55 control subjects. Associations between the presence of particular NR3C1 genotypes and alleles and MM prevalence as well as prognostic factors, such as WHO classification, creatinine levels, and the Durie–Salmon staging system, were evaluated. The G allele for BclI and the A allele for N363S were found to be significantly linked with an increased risk of MM (p = 0.0281 and 0.0000, respectively). There were no associations between genotype/allele frequencies and prognostic factors except the presence of allele G for BclI and higher level of CRP (p = 0.0435). Statistical analysis did not show any connections between the presence of particular genotype for BclI and overall survival time of MM patients. The investigated polymorphisms of the NR3C1 gene have major influences on MM development risk. However, BclI does not affect the response to VAD therapy.

Journal

Comparative Clinical Pathology – Springer Journals

Published: Dec 13, 2011

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