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

Summary 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 ( SNP s) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects ( AE s) 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 AE s 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 SNP s may be useful in assessing the probability of AE s in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM .