title: The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients.
abstract: The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy. Six single-nucleotide polymorphisms (SNPs), including COMT (rs165599, rs4680, rs737865), APOE (rs429358, rs7412), and BDNF (rs6265), were evaluated. The scores of breast cancer patients after chemotherapy were poorer in comparison to those before chemotherapy (t = -5.317, z = -3.372, respectively,P< 0.01), and the scores of TNBC patients were poorer than those of NTNBC patients were after chemotherapy (t = -5.997, z = -5.284, respectively,P< 0.01). Patients with the COMT (rs165599) genotype had a significantly lower chance of developing cognitive decline than the patients with the G/G genotype, and this was linear with the retrospective memory (RM) questionnaires (β = -1.441, CI (95%) = -2.781~-0.101). However, there was no significant difference between the memory scores of APOE (rs429358, rs7412) and BDNF (rs6265) carriers before or after chemotherapy. This study suggests that CICI in TNBC patients was more prominent than that in NTNBC patients after chemotherapy, and the COMT (rs165599) polymorphism was linear to the retrospective memory (RM) questionnaires, and may be a potential genetic marker for increased vulnerability to CICI in TNBC patients.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University Hefei 230601, Anhui, China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University Hefei 230601, Anhui, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University Hefei 230601, Anhui, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gan
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University Hefei 230601, Anhui, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University Hefei 230601, Anhui, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Neuropsychological Laboratory, Department of Neurology, The First Affiliated Hospital of Anhui Medical University Hefei 230022, Anhui, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
keywords: Catechol-O-methyl transferase; breast cancer; chemotherapy-induced cognitive impairment; polymorphisms