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

Leukemia. 2009 Oct;23(10):1913-9. doi: 10.1038/leu.2009.129. Epub 2009 Aug 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Bone Diseases / genetics*
  • CD30 Ligand / genetics*
  • Clinical Trials, Phase III as Topic
  • Epoxide Hydrolases / genetics*
  • Gene Expression Profiling
  • Glycogen Synthase Kinase 3 / genetics*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Multiple Myeloma / complications
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • CD30 Ligand
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • TNFSF8 protein, human
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Epoxide Hydrolases
  • EPHX1 protein, human