Symptoms Biology Unit, Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland, USA.
Department of Biostatistics, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Cancer Med. 2024 Jan;13(2):e6975. doi: 10.1002/cam4.6975.
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.
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.
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.
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.
乳腺癌幸存者(BCS)在完成主要癌症治疗(尤其是化疗)期间甚至数月后经常抱怨与癌症相关的认知障碍(CRCI)。CRCI 的病因尚不清楚,但已有报道称 CRCI 与种系遗传多态性有关,包括脑源性神经营养因子(BDNF)rs6265 多态性。本研究调查了特定 BDNF rs6265 与 CRCI 的关联。
使用认知症状的主观报告(患者报告的结果测量信息系统®第 1.0 版,8 项简短形式)和计算机化的客观认知功能评分(CANTAB®)评估与癌症相关的认知障碍。从口腔拭子中确定 BDNF rs6265 基因型。通过单因素方差分析或 Kruskal-Wallis 检验,然后进行事后检验和基于秩的回归分析,检查特定 BDNF rs6265 与 CRCI 的关联。
我们检查了 356 名女性 BCS。平均(SD)年龄为 55.6(9.8)岁,癌症诊断后中位数(IQR)为 4.0(6.0)年,331 名(92.7%)自我描述为白人。携带 Met/Met 基因型的 BCS 在“视觉情节记忆和新学习”和“空间工作记忆和执行功能”方面表现较差。这种关系无论是否接受过化疗都存在。
我们的研究结果表明,携带 BDNF rs6265 Met/Met 基因型会增加 BCS 发生 CRCI 的风险。这些结果具有基础性,为确定 CRCI 的潜在机制提供了重要信息。