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

• Published in: Leukemia research Vol. 35; no. 9; pp. 1178 - 1183
• Main Authors: Cibeira, María Teresa, Fernández de Larrea, Carlos, Navarro, Alfons, Díaz, Tania, Fuster, Dolors, Tovar, Natalia, Rosiñol, Laura, Monzó, Mariano, Bladé, Joan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2011
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors - therapeutic use; DNA repair; DNA Repair - genetics; Drug Resistance, Neoplasm - genetics; Female; Hematology, Oncology and Palliative Medicine; Humans; Male; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - genetics; Myeloma; Polymorphism, Single Nucleotide - physiology; Recurrence; Response; SNP; Survival; Survival Analysis; Thalidomide; Thalidomide - therapeutic use; Treatment Failure; Treatment Outcome; Response; SNP; Myeloma; Thalidomide; DNA repair; Survival
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2011.02.009

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).