The COMT Genetic Factor Regulates Chemotherapy-Related Prospective Memory Impairment in Survivors With HER2−/+ Breast Cancer

Abstract

BackgroundPrevious 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.ObjectiveThe current research aimed to evaluate the regulation of the risk by COMT genotype on CRCI in breast cancer survivors with disparate status of HER2.MethodsBreast 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).ResultsThe EBPM and TBPM performances was lower as compared with these before chemotherapy (z = −7.712, z = −2.403, respectively, p < 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, p < 0.01; z = −2.205 p < 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, p = 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.ConclusionThe 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.

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study

“…Other factors have been proposed to contribute to cognitive problems after surgery but before systemic therapy, including effects of general anesthesia [37,38], genotype [39], and differential in ammatory effects related to extent of resection [40]. This latter effect has been particularly pronounced in pre-clinical models with aged animals [41].…”

The correlation between neutrophil-to-lymphocyte ratio, carcinoembryonic antigen, and carbohydrate antigen 153 levels with chemotherapy-related cognitive impairment in early-stage breast cancer patients

“…DNA damage of the central nervous system induced by chemotherapy is one of the essential mechanisms of CRCI in BC ( 40 ). The gene polymorphism of apolipoprotein E (ApoE), catechol-O-methyl-transferase (COMT), and BDNF was associated with CRCI ( 16 , 30 , 41 ). FMRI study found that the PM impairment in patients with BC was related to the abnormality of the brain network in the hippocampus and poor connection with prefrontal brain function after chemotherapy ( 42 ).…”

A Systematic Review Focusing on Understanding the Effects of a Defined Set of Non-Modifiable Factors in Patients who Suffer from Chemotherapy Induced Cognitive Impairments or “Chemobrain”

“…This led to the conclusion that this allele, the APOE e2 genotype, provided a protective bene t on cognition (β = 0.32, 95% CI = 0.00 to 0.65). 13 Carroll 15 Overall, the ndings from the included studies suggest that increased leukocyte circulation, the DNMT1 rs2162560 A allele, 11 ER-/PR-genotype, HERgenotype, and increased DNA methylation-especially at the CpG regions-leads to increased complaints of CICI in BCPs and survivors. 12 Furthermore, having the APOE e2 genotype serves as a protective factor against CICI.…”

“…[11][12][13] For example, Yao et al and Chan et al observed the protective effect of DNA methylation 12. Van Dyke et al andLi et al correlate APOE to CICI, but differ in their ndings 13,15. Li et al additionally explores COMT polymorphisms with regards to increased CICI risk 15.…”