BDNF SNP Val66Met and Bassline Serum Protein Levels Predict Subjective and Objective Symptoms of Chemotherapy-induced Peripheral Neuropathy in Patients with Lymphoma and Myeloma

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect and a dose-limiting factor in haematological malignancies (HM). Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for nervous system maintenance. Aim: We evaluated the role of BDNF gene single nucleotide polymorphism (Val66Met-SNP) and peripheral blood (PB) BDNF in CIPN-developing non-Hodgkin lymphoma (NHL) and Multiple Myeloma (MM) patients. Methods: CIPN was assessed in 45 patients (33 NHL and 12 MM patients) at diagnosis, and along of vincristine or bortezomib-based therapy, using the Total Neuropathy Score (TNSr) and Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx). Depression was assessed using PHQ9 questionnaire. Val66Met-SNP and BDNF protein levels were quantified using Sanger sequencing and ELISA, respectively. Results: No genotype-dependent difference in baseline/maximal TNSr was found. Met-BDNF patients showed significantly lowered maximal FACT-GOG-NTx and PHQ9 scores compared to Val-BDNF patients. Significant inverse correlation was revealed between baseline BDNF protein levels and maximal TNSr, FACT-GOG-NTx and PHQ9 scores in both genotypes (r=0.608, p=0.0001; r=0.607, p=0.0001, r=0.461, p=0.004 for TNSr, FACT-GOG-NTx and PHQ9, respectively). Such correlation was not demonstrated with the number of platelets which are known to be the main compartment of BDNF in the peripheral blood. Increase baseline/maximal TNSr and maximal FACT-GOG-NTx in patients with diabetes was noted in parallel to a decrease in their BDNF protein levels. Conclusions: Our results suggest association between Met-BDNF SNP and lower depression and CIPN perception. In both genotypes, higher baseline PB-BDNF levels may protect against CIPN development.