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Catechol-O-Methyltransferase Gene Polymorphisms and the Risk of Chemotherapy-Induced Prospective Memory Impairment in Breast Cancer Patients with Varying Tumor Hormonal Receptor Expression.

ABSTRACT: 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.

SUBMITTER: Li W

PROVIDER: S-EPMC7531203 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Catechol-O-Methyltransferase Gene Polymorphisms and the Risk of Chemotherapy-Induced Prospective Memory Impairment in Breast Cancer Patients with Varying Tumor Hormonal Receptor Expression.

Li Wen W Zhao Jingjing J Ding Ke K Chao Herta H HH Li Chiang-Shan R CR Cheng Huaidong H Shen Li L

Medical science monitor : international medical journal of experimental and clinical research 20200928

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 prese ...[more]

PMID: 32985495

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Project description:Background & aimsThe etiology of abdominal pain in postinfectious, diarrhea-predominant irritable bowel syndrome (PI-IBS-D) is unknown, and few treatment options exist. Catechol-O-methyltransferase (COMT), an enzyme that inactivates and degrades biologically active catecholamines, plays an important role in numerous physiologic processes, including modulation of pain perception. Our objective was to determine the mechanism(s) of how decreased colonic COMT in PI-IBS-D patients contributes to the chronic abdominal pain phenotype after enteric infections.MethodsColon neurons, epithelial cells, and macrophages were procured with laser capture microdissection from PI-IBS-D patients to evaluate cell-specific colonic COMT, microRNA-155 (miR-155), and tumor necrosis factor (TNF) α expression levels compared to recovered patients (infection cleared: did not develop PI-IBS-D) and control individuals. COMT-/-, colon-specific COMT-/-, and miR-155-/- mice and human colonoids were used to model phenotypic expression of COMT in PI-IBS-D patients and to investigate signaling pathways linking abdominal pain. Citrobacter rodentium and trinitrobenzene sulfonic acid animal models were used to model postinflammatory changes seen in PI-IBS-D patients.ResultsColonic COMT levels were significantly decreased and correlated with increased visual analog scale abdominal pain ratings in PI-IBS-D patients compared to recovered patients and control individuals. Colonic miR-155 and TNF-α were increased in PI-IBS-D patients with diminished colonic COMT. COMT-/- mice had significantly increased expression of miR-155 and TNF-α in both colon tissues and dorsal root ganglia. Introduction of cV1q antibody (anti-TNF-α) into mice reversed visceral hypersensitivity after C rodentium and trinitrobenzene sulfonic acid.ConclusionsDecreased colonic COMT in PI-IBS-D patients drives abdominal pain phenotypes via the COMT/miR-155/TNF-α axis. These important findings will allow new treatment paradigms and more targeted and personalized medicine approaches for gastrointestinal disorders after enteric infections.

Dataset Information

Catechol-O-Methyltransferase Gene Polymorphisms and the Risk of Chemotherapy-Induced Prospective Memory Impairment in Breast Cancer Patients with Varying Tumor Hormonal Receptor Expression.

Publications

Catechol-O-Methyltransferase Gene Polymorphisms and the Risk of Chemotherapy-Induced Prospective Memory Impairment in Breast Cancer Patients with Varying Tumor Hormonal Receptor Expression.

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