儿茶酚-O-甲基转移酶基因因素调节HER2-/+乳腺癌幸存者中与化疗相关的前瞻性记忆损害。
The COMT Genetic Factor Regulates Chemotherapy-Related Prospective Memory Impairment in Survivors With HER2-/+ Breast Cancer.
作者信息
Li Wen, Zhang Qianqian, Cai Yinlian, Chen Tingting, Cheng Huaidong
机构信息
Cancer Treatment Center, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
出版信息
Front Oncol. 2022 Feb 8;12:816923. doi: 10.3389/fonc.2022.816923. eCollection 2022.
BACKGROUND
Previous findings indicated that polymorphism in gene catechol-O-methyltransferase (COMT) had been linked to chemotherapy-related cognitive impairment (CRCI). Nevertheless, the motivation of COMT polymorphisms in regulating cognitive impairment in breast cancer survivors with disparate status of human epidermal growth factor receptor 2 (HER2) was still vague.
OBJECTIVE
The current research aimed to evaluate the regulation of the risk by COMT genotype on CRCI in breast cancer survivors with disparate status of HER2.
METHODS
Breast cancer survivors (103 with HER2- and 118 with HER2+) underwent neuropsychological tests before and after chemotherapy, containing event- and time-based prospective memory (EBPM and TBPM). Three single-nucleotide polymorphisms (SNPs) were estimated by providing peripheral blood, containing COMT (rs165599, rs737865, and rs4680).
RESULTS
The EBPM and TBPM performances was lower as compared with these before chemotherapy (z = -7.712, z = -2.403, respectively, < 0.01). Furthermore, the EBPM and TBPM performances of HER2- group survivors were lower than those of HER2+ group survivors after chemotherapy (z = -7.181, < 0.01; z = -2.205 < 0.05, respectively). The survivors with COMT (rs165599) A/A genotype carriers had a meaningfully poorer chance of memory descend [dominant model: adjusted, OR = 2.21, CI (95%) = 1.156-4.225, = 0.016] and showed better on TBPM test, relative to G/G genotype. Patients with the COMT (rs737865) A/G and G/G genotype showed protective function than the patients with the A/A and performed better on MMSE and TBPM tests.
CONCLUSION
The types of HER2 may be correlated to chemotherapy-related prospective memory impairments in breast cancer survivors. Furthermore, the COMT (rs165599, rs737865) polymorphisms were correlated to the risk of TBPM decline scores and possibly be a potential genetic identifying for increasing risk of CRCI in breast cancer patients with disparate status of HER2.
背景
先前的研究结果表明，儿茶酚-O-甲基转移酶（COMT）基因多态性与化疗相关认知障碍（CRCI）有关。然而，COMT基因多态性在调节人类表皮生长因子受体2（HER2）状态不同的乳腺癌幸存者认知障碍中的作用仍不明确。
目的
本研究旨在评估COMT基因型对HER2状态不同的乳腺癌幸存者CRCI风险的调节作用。
方法
乳腺癌幸存者（HER2阴性103例，HER2阳性118例）在化疗前后接受神经心理学测试，包括基于事件和基于时间的前瞻性记忆（EBPM和TBPM）。通过提供外周血估计三个单核苷酸多态性（SNP），包括COMT（rs165599、rs737865和rs4680）。
结果
与化疗前相比，EBPM和TBPM表现较低（z分别为-7.712、-2.403，P<0.01）。此外，化疗后HER2阴性组幸存者的EBPM和TBPM表现低于HER2阳性组幸存者（z分别为-7.181，P<0.01；z为-2.205，P<0.05）。与G/G基因型相比，COMT（rs165599）A/A基因型携带者的记忆下降几率显著更高[显性模型：校正后，OR=2.21，CI（95%）=1.156-4.225，P=0.016]，且在TBPM测试中表现更好。COMT（rs73786⑤）A/G和G/G基因型患者比A/A基因型患者具有保护作用，在MMSE和TBPM测试中表现更好。
结论
HER2类型可能与乳腺癌幸存者化疗相关的前瞻性记忆障碍有关。此外，COMT（rs165599、rs737865）多态性与TBPM下降评分风险相关，可能是HER2状态不同的乳腺癌患者CRCI风险增加的潜在遗传标志物。
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