Met alleles on BDNF may protect against cancer-related cognitive impairment

The Val6Met polymorphism (rs6265) in the brain-derived neurotrophic factor (BDNF) appears to be protective against cancer-related cognitive impairment (CRCI) after chemotherapy, according to a recent Singapore study.

“Plasma BDNF and the BDNF Met allele confer protective effects against subjective CRCI,” the researchers said. “The results also suggest that the Met allele prevents the reduction of plasma BDNF during chemotherapy,” they added.

The study included 174 early-stage breast cancer patients (mean age, 51.8±8.91 years) who underwent subjective and objective assessments of cognitive function. Three months after chemotherapy initiation, 45 patients showed overall subjective CRCI, yielding a rate of 25.9 percent. Nineteen and 22 patients showed delayed and persistent overall CRCI, respectively. [Breast Cancer Res Treat 2020;doi:10.1007/s10549-020-05807-y]

More than half (52.9 percent; n=174) of the enrolled participants had the Val/Met genotype, and 45 (25.9 percent) had the Val/Val genotype; only 37 (21.3 percent) had the Met/Met BDNF genotype.

In patients who had developed CRCI at the 3-month follow-up, the researchers observed a significant drop in plasma BDNF levels from baseline (p<0.01). Such change was also detectable in those with persistent CRCI, but not in patients with delayed CRCI.

BDFN analysis according to genotype showed that the percentage of patients who saw a reduction in plasma BDNF shared an inverse interaction with the frequency of the Met allele. For example, 82.2 percent of those carrying the Val/Val genotype saw decreasing BDNF, as opposed to 79.3 percent and 67.6 percent of patients with the Val/Met and Met/Met genotypes, respectively.

Logistic regression analysis revealed that the risk of developing overall subjective CRCI 3 months after starting chemotherapy was significantly lower in those who saw smaller magnitudes in BDNF reduction (odds ratio [OR], 0.88, 95 percent confidence interval [CI], 0.79–0.99; p=0.041). Carriers of the Met allele also showed a lower likelihood of developing subjective CRCI in the domains of multitasking (OR, 0.30, 95 percent CI, 0.12–0.71; p=0.007) and memory (OR, 0.27, 95 percent CI, 0.10–0.79; p=0.016).

Regression analyses were adjusted for confounders, such as age, race, education, anxiety and depression, fatigue, radiation treatment, and insomnia.

Notably, researchers found no statistical link of plasma BDNF or the rs6265 polymorphism with objective CRCI.

“This is the first study to detail an association between plasma BDNF and rs6265 in long-term, postchemotherapy CRCI,” the researchers said, pointing out that their findings uncover a potentially protective effect of the Met allele against delayed or persistent subjective CRCI.

“This study provides a basis for future clinical studies to investigate the effects of BDNF on long-term CRCI and the possible implementation of early intervention strategies to increase BDNF levels among patients at risk of long-term CRCI during survivorship,” they added.