PMID- 31115923
OWN - NLM
STAT- MEDLINE
DCOM- 20200716
LR  - 20200716
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 186
IP  - 5
DP  - 2019 Sep
TI  - Polymorphisms in the promotor region of the CRBN gene as a predictive factor for 
      peripheral neuropathy in the course of thalidomide-based chemotherapy in multiple 
      myeloma patients.
PG  - 695-705
LID - 10.1111/bjh.15972 [doi]
AB  - Thalidomide is commonly used in treatment of multiple myeloma (MM). This study 
      aimed to analyse the influence of clinical and molecular factors - single 
      nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the 
      risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with 
      MM. The study group included 82 patients receiving CTD (thalidomide, 
      cyclophosphamide, dexamethasone) as first line treatment. The intensity of 
      haematological and non-haematological AEs was assessed according to the Common 
      Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that 
      patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher 
      risk of peripheral polyneuropathy compared to patients with other variants of the 
      investigated SNP [odds ratio (OR) = 14.29]. Carriers of this genotype were 
      burdened with significantly (about 17-fold) higher risk of diarrhoea during 
      treatment (OR = 16.67). The presence of CRBN AA (rs6768972) or TT (rs1672753) 
      genotypes was associated with about 333-fold and 250-fold lower risk of 
      constipation in the course of therapy (OR = 0.003; OR = 0.004, respectively). 
      Selected CRBN SNPs may be useful in assessing the probability of AEs in the form 
      of peripheral polyneuropathy and gastrointestinal motility disorders associated 
      with the use of thalidomide in patients with MM.
CI  - (c) 2019 British Society for Haematology and John Wiley & Sons Ltd.
FAU - Mlak, Radoslaw
AU  - Mlak R
AUID- ORCID: 0000-0001-7399-8340
AD  - Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
FAU - Szudy-Szczyrek, Aneta
AU  - Szudy-Szczyrek A
AUID- ORCID: 0000-0003-2352-394X
AD  - Department of Haemato-oncology and Bone Marrow Transplantation, Medical 
      University of Lublin, Lublin, Poland.
FAU - Mazurek, Marcin
AU  - Mazurek M
AD  - Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
FAU - Szczyrek, Michal
AU  - Szczyrek M
AD  - Department of Pneumonology, Oncology and Allergology, Medical University of 
      Lublin, Lublin, Poland.
FAU - Homa-Mlak, Iwona
AU  - Homa-Mlak I
AD  - Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
FAU - Mielnik, Michal
AU  - Mielnik M
AD  - Department of Haemato-oncology and Bone Marrow Transplantation, Medical 
      University of Lublin, Lublin, Poland.
FAU - Chocholska, Sylwia
AU  - Chocholska S
AD  - Department of Haemato-oncology and Bone Marrow Transplantation, Medical 
      University of Lublin, Lublin, Poland.
FAU - Jankowska-Lecka, Olga
AU  - Jankowska-Lecka O
AD  - Department of Haemato-oncology and Bone Marrow Transplantation, Medical 
      University of Lublin, Lublin, Poland.
FAU - Malecka-Massalska, Teresa
AU  - Malecka-Massalska T
AD  - Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
FAU - Hus, Marek
AU  - Hus M
AD  - Department of Haemato-oncology and Bone Marrow Transplantation, Medical 
      University of Lublin, Lublin, Poland.
LA  - eng
PT  - Journal Article
DEP - 20190522
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Immunosuppressive Agents)
RN  - 4Z8R6ORS6L (Thalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/*genetics/mortality
MH  - Peripheral Nervous System Diseases/*chemically induced/*genetics/mortality
MH  - Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic
MH  - Survival Rate
MH  - Thalidomide/administration & dosage/*adverse effects
OTO - NOTNLM
OT  - CRBN protein
OT  - SNPs
OT  - adverse effects
OT  - multiple myeloma
OT  - peripheral neuropathy
OT  - thalidomide
EDAT- 2019/05/23 06:00
MHDA- 2020/07/17 06:00
CRDT- 2019/05/23 06:00
PHST- 2019/02/01 00:00 [received]
PHST- 2019/03/19 00:00 [accepted]
PHST- 2019/05/23 06:00 [pubmed]
PHST- 2020/07/17 06:00 [medline]
PHST- 2019/05/23 06:00 [entrez]
AID - 10.1111/bjh.15972 [doi]
PST - ppublish
SO  - Br J Haematol. 2019 Sep;186(5):695-705. doi: 10.1111/bjh.15972. Epub 2019 May 22.