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

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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: […]