Associations of brain-derived neurotrophic factor rs6265 polymorphism and cognitive function in breast cancer survivors from a cross-sectional study

Abstract

Background: Breast cancer survivors (BCS) often complain of cancer-related cognitive impairment (CRCI) during and even months after completing primary cancer treatments, particularly chemotherapy. The etiology of CRCI is unknown, but associations of CRCI with germline genetic polymorphisms have been reported, including Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism. The current study investigated the associations of specific BDNF rs6265 with CRCI.

Methods: Cancer-related cognitive impairment was assessed using subjective reports of cognitive symptoms (the version 1.0, 8-item short-forms of the Patient-Reported Outcomes Measurement Information System®) and computerized objective cognitive function scores (CANTAB®). BDNF rs6265 genotypes were determined from buccal swabs. The associations of specific BDNF rs6265 with CRCI were examined by either one-way analysis of variance or the Kruskal–Wallis test followed by post hoc tests and rank-based regression analysis.

Results: We examined 356 female BCS. The mean (SD) age was 55.6 (9.8) years old, the median (IQR) years since cancer diagnosis were 4.0 (6.0), and 331 (92.7%) were self-described as White. BCS carrying the Met/Met genotype showed poorer results on ‘visual episodic memory and new learning’ and ‘spatial working memory and executive function.’ This relationship was observed regardless of prior chemotherapy.

Conclusion: Our findings suggest that carrying the BDNF rs6265 Met/Met genotype increases the risk for CRCI in BCS. These results are foundational in nature and provide important information to identify mechanisms underpinning CRCI.