Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Autor: Tan CJ; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Lim SWT; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Toh YL; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Ng T; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Yeo A; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Shwe M; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Foo KM; Department of Pharmacy, K.K. Women's and Children's Hospital, Singapore, Singapore., Chu P; Singapore Cord Blood Bank, Singapore, Singapore., Jain A; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Koo SL; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Dent RA; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Ng RCH; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Yap YS; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Lim EH; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Loh KW; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Chay WY; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Lee GE; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Tan TJY; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Beh SY; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Wong M; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Chan JJ; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Khor CC; Human Genetics, Genome Institute of Singapore, Singapore, Singapore.; Glaucoma Research Group, Singapore Eye Research Institute, Singapore, Singapore., Ho HK; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore., Chan A; Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Singapore. phaac@nus.edu.sg.; Department of Pharmacy, National Cancer Centre, Singapore, Singapore. phaac@nus.edu.sg.; Duke-NUS Graduate Medical School, Singapore, Singapore. phaac@nus.edu.sg.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2019 Jul; Vol. 56 (7), pp. 4741-4750. Date of Electronic Publication: 2018 Oct 31.
DOI: 10.1007/s12035-018-1410-4
Abstrakt: Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology.
Databáze: MEDLINE
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