Impact on response and survival of DNA repair single nucleotide polymorphisms in relapsed or refractory multiple myeloma patients treated with thalidomide

Leuk Res. 2011 Sep;35(9):1178-83. doi: 10.1016/j.leukres.2011.02.009. Epub 2011 Mar 23.

Abstract

Single nucleotide polymorphisms (SNPs) in 12 genes involving multidrug resistance, drug metabolic pathways, DNA repair systems and cytokines were examined in 28 patients with relapsed/refractory multiple myeloma (MM) treated with single agent thalidomide and the results were correlated with response, toxicity and overall survival (OS). The response rate was higher in patients with SNPs in ERCC1 (rs735482) (p=0.006), ERCC5 (rs17655) (p=0.04) or XRCC5 (rs1051685) (p=0.013). Longer OS was associated with the SNP in ERCC1 (rs735482) (p=0.005) and XRCC5 (rs1051685) (p=0.02). Finally, polymorphism in GSTT1 (rs4630) was associated with a lower frequency of thalidomide-induced peripheral neuropathy (p=0.04).

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use
  • DNA Repair / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics*
  • Polymorphism, Single Nucleotide* / physiology
  • Recurrence
  • Survival Analysis
  • Thalidomide / therapeutic use*
  • Treatment Failure
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Thalidomide