Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer

Abstract

BackgroundBrain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment.MethodsOverall, 145 patients receiving chemotherapy for early-stage breast cancer (mean age: 50.8 ± 8.8 y; 82.1% Chinese) were recruited. Patients' cognitive functions were assessed longitudinally using the validated Functional Assessment of Cancer Therapy–Cognitive Function (v.3) and an objective computerized tool, Headminder. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition after adjusting for ethnicity and clinically important covariates.ResultsOf the 145 patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met genotype was associated with statistically significant lower odds of developing cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08–0.92; P = .036). The Met carriers were less likely to experience impairment in the domains of verbal fluency (OR = 0.34; 95% CI: 0.12–0.90; P = .031) and multitasking ability (OR = 0.37; 95% CI: 0.15–0.91; P = .030) compared with the Val/Val homozygote. No associations were observed between Headminder and the BDNF Val66Met polymorphism.ConclusionsThis is the first study to provide evidence that carriers of the BDNF Met allele are protected against chemotherapy-associated cognitive impairment. Further studies are required to validate the findings.

Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression

“…[1–3] As several studies have shown, memory impairment is the most prominent presentation of chemotherapy-induced cognitive impairment (CICI) in patients with breast cancer, [2,4,5] and acts as an important factor affecting the long-term quality of life in these patients. [6] …”

Chemotherapy‐associated cognitive impairments in Korean cancer patients: Risk factors and functional outcome

“…It derived from data with Chinese‐based Asian cancer patients . Because the original study defined the minimal clinically important difference only for the FACT‐cog total score (4.7%‐7.2%), subsequent study by the same team chose 15% reduction as the cut‐off for the cognitive‐impairment subscale, twice the largest minimal clinically important difference for the total scale. This was a reasonably conservative cut‐off considering that average change on the impairment subscale was twice larger than other subscales .…”

“…Multiple factors contribute to cognitive decline in cancer patients . Recent studies examined other risk factors: menopausal status and various endocrine therapies, health behaviors (such as exercise), cytokines, and genetic predisposing factors . Longitudinal studies investigating their effects can clarify the complex mechanisms of cognitive decline in cancer patients.…”

“…Yet, this method can be biased because the distribution of the sample influences the value. Thus, we used a 15% reduction from baseline score, suggested based on a previous analysis of the minimal clinically important differences for the selected measure: the Functional Assessment of Cancer Therapy‐Cognitive Function . Follow‐up took place during the course of treatment; the sample included various cancer types, allowing examination of the relative risk of particular cancer types.…”

Chemotherapy-induced neurotoxicity in pediatric solid non-CNS tumor patients: An update on current state of research and recommended future directions

“…The APOE-gene on the other hand, encodes for Apolipoprotein E, a glycolipoprotein that plays an important role in neuronal repair and neuroplasticity [109]. More specifically, patients who carry an ε4 allele show increased neurotoxic vulnerability to chemotherapy when compared to the ones who do not [110].Polymorphisms of the BDNF (Brain-Derived-Neurotrophic-Factor)-gene were recently also associated with neuroprotection against the toxic effects of chemotherapy [111].…”