Genetic polymorphisms of EPHX1, Gsk3beta, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma.

Publication Type:

Journal Article

Source:

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, Volume 23, Issue 10, p.1913-9 (2009)

Keywords:

2009, Bone Diseases, CD30 Ligand, Center-Authored Paper, Clinical Trials, Phase III as Topic, Epoxide Hydrolases, Gene Expression Profiling, Glycogen Synthase Kinase 3, Humans, Intercellular Signaling Peptides and Proteins, Multiple Myeloma, Polymorphism, Single Nucleotide, Prospective Studies, Public Health Sciences Division, Survival Rate, Tumor Markers, Biological

Abstract:

Bone disease in myeloma occurs as a result of complex interactions between myeloma cells and the bone marrow microenvironment. A custom-built DNA single nucleotide polymorphism (SNP) chip containing 3404 SNPs was used to test genomic DNA from myeloma patients classified by the extent of bone disease. Correlations identified with a Total Therapy 2 (TT2) (Arkansas) data set were validated with Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) data sets. Univariate correlates with bone disease included: EPHX1, IGF1R, IL-4 and Gsk3beta. SNP signatures were linked to the number of bone lesions, log(2) DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: EPHX1 (P=0.0026); log(2) DKK-1 expression (P=0.0046); serum lactic dehydrogenase (LDH) (P=0.0074); Gsk3beta (P=0.02) and TNFSF8 (P=0.04) were linked to bone disease. This assessment of genetic polymorphisms identifies SNPs with both potential biological relevance and utility in prognostic models of myeloma bone disease.