Li Wen, Zhao Jingjing, Ding Ke, Chao Herta H, Li Chiang-Shan R, Cheng Huaidong, Shen Li
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China (mainland).
Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Med Sci Monit. 2020 Sep 28;26:e923567. doi: 10.12659/MSM.923567.
BACKGROUND Existing research evidence indicates that breast cancer patients have different degrees of cognitive dysfunction after chemotherapy, and polymorphisms in 3 genes (catechol-O-methyltransferase, COMT; apolipoprotein E, APOE; and brain-derived neurotrophic factor, BDNF) have been associated with cognitive impairment. However, the role of these 3 gene polymorphisms in modulating cognitive impairment in breast cancer survivors with varying hormonal receptor expression is not clear at present. To explore the effects of genetic polymorphisms in BDNF, APOE, and COMT on the regulation of prospective memory impairments induced by chemotherapy in breast cancer patients with various expression levels of estrogen receptor (ER) and progesterone receptor (PR). MATERIAL AND METHODS A total of 232 patients with breast cancer (113 with ER-/PR- and 119 with ER+/PR+) were evaluated before and after chemotherapy for cognitive function, including prospective memory. Following previously published sequencing procedures, we assessed 6 single-nucleotide polymorphisms (SNPs), including BDNF (rs6265), APOE (rs429358, rs7412), and COMT (rs165599, rs4680, rs737865). RESULTS The patients showed poorer prospective memory scores after chemotherapy than before chemotherapy. Furthermore, the ER-/PR- group showed poorer event-based prospective memory (EBPM) scores than the ER+/PR+ group (z=-7.831, p<0.01) after chemotherapy. The patients with the COMT rs737865G/G genotype, compared with those with the A/A and A/G genotypes, showed a linear EBPM performance (ß=1.499, 95% confidence interval (CI)=1.017~2.211) and were less likely to have memory impairment. In contrast, APOE and BDNF polymorphisms did not influence cognitive performance. CONCLUSIONS The patterns of hormonal receptor expression may be related to prospective memory impairments induced by chemotherapy in breast cancer patients. Furthermore, the COMT polymorphism (rs737865) was linearly related to the extent of deficits in EBPM and may represent a potential genetic marker of risk for cognitive deficits triggered by chemotherapy in patients with breast cancer.
背景 现有研究证据表明，乳腺癌患者化疗后存在不同程度的认知功能障碍，3个基因（儿茶酚-O-甲基转移酶，COMT；载脂蛋白E，APOE；脑源性神经营养因子，BDNF）的多态性与认知损害有关。然而，目前尚不清楚这3种基因多态性在调节不同激素受体表达的乳腺癌幸存者认知损害中的作用。为了探讨BDNF、APOE和COMT基因多态性对不同雌激素受体（ER）和孕激素受体（PR）表达水平的乳腺癌患者化疗所致前瞻性记忆损害的调节作用。
材料与方法 共纳入232例乳腺癌患者（113例ER-/PR-和119例ER+/PR+），在化疗前后评估其认知功能，包括前瞻性记忆。按照先前发表的测序程序，我们评估了6个单核苷酸多态性（SNP），包括BDNF（rs6265）、APOE（rs429358、rs7412）和COMT（rs165599、rs4680、rs737865）。
结果 患者化疗后的前瞻性记忆得分低于化疗前。此外，化疗后ER-/PR-组的事件性前瞻性记忆（EBPM）得分低于ER+/PR+组（z=-7.831，p<0.01）。与A/A和A/G基因型患者相比，COMT rs737865G/G基因型患者表现出线性的EBPM表现（β=1.499，95%置信区间（CI）=1.017~2.211），且记忆损害的可能性较小。相比之下，APOE和BDNF多态性不影响认知表现。
结论 激素受体表达模式可能与乳腺癌患者化疗所致的前瞻性记忆损害有关。此外，COMT多态性（rs737865）与EBPM缺陷程度呈线性相关，可能是乳腺癌患者化疗引发认知缺陷风险的潜在遗传标志物。
