Oncotarget

Research Papers:

Polymorphisms in the promoter region of the CRBN gene as a predictive factor for the first-line CTD therapy in multiple myeloma patients

Aneta Szudy-Szczyrek _, Radosław Mlak, Michał Szczyrek, Sylwia Chocholska, Jacek Sompor, Adam Nogalski, Teresa Małecka-Massalska and Marek Hus

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Oncotarget. 2018; 9:24054-24068. https://doi.org/10.18632/oncotarget.25307

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Abstract

Aneta Szudy-Szczyrek1, Radosław Mlak2, Michał Szczyrek3,4, Sylwia Chocholska1, Jacek Sompor5, Adam Nogalski5, Teresa Małecka-Massalska2 and Marek Hus1

1Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland

2Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland

3Department of Internal Medicine in Nursing, Medical University of Lublin, 20-090 Lublin, Poland

4Department of Pneumology, Oncology and Allergology, Medical University of Lublin, 20-950 Lublin, Poland

5Department of Trauma Surgery and Emergency Medicine, Medical University of Lublin, 20-081 Lublin, Poland

Correspondence to:

Aneta Szudy-Szczyrek, email: anetaszudy@gmail.com

Keywords: multiple myeloma; thalidomide; cereblon; polymorphism

Received: February 21, 2018    Accepted: April 16, 2018    Published: May 08, 2018

ABSTRACT

Cereblon is a primary molecular target for immunomodulatory drugs. The aim of this study was to evaluate the influence of selected clinical and molecular factors including single nucleotide polymorphisms (SNPs) in CRBN gene on the efficacy of first line CTD (cyclophosphamide, thalidomide, dexamethasone) chemotherapy in patients with multiple myeloma. Study group consisted of 68 patients. Analysis of CRBN gene SNPs (rs6768972, rs1672753) was performed using Real-Time PCR genotyping technique. Median progression free survival (PFS) was 15 months and overall survival (OS) 79 months. Factors associated with significantly shorter OS included ISS 3, kidney disease, weight loss, anemia, thrombocytopenia, hypoalbuminemia, elevated β2-microglobuline and CRP. The presence of t(4;14) was associated with significantly shorter PFS and OS. Both examined SNPs proved to be statistically significant, independent predictive factors of efficacy of the CTD chemotherapy. The presence of AA genotype (rs6768972) correlated with longer median PFS (18 vs 9 months; HR=0.49,95% CI: 0.26-0.91, p=0.0062). Conversely, in the carriers of CC genotype (rs1672753) significantly shorter median PFS was observed (4 vs 16 months; HR=3.93, 95% CI: 0.26-59.64, p=0.0321). In conclusion, SNPs of the CRBN gene may be useful in qualifying patients for treatment with regimens containing thalidomide.


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