Associations of plasma brain-derived neurotrophic factor (BDNF) and Val66Met polymorphism (rs6265) with long-term cancer
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EPIDEMIOLOGY
Associations of plasma brain‑derived neurotrophic factor (BDNF) and Val66Met polymorphism (rs6265) with long‑term cancer‑related cognitive impairment in survivors of breast cancer Ning Yi Yap1 · Nichole Yue Ting Tan1 · Chia Jie Tan1 · Kiley Wei‑Jen Loh2 · Raymond Chee Hui Ng2,3 · Han Kiat Ho1 · Alexandre Chan4,5 Received: 4 February 2020 / Accepted: 11 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Brain-derived neurotrophic factor (BDNF) and the BDNF Val66Met polymorphism (rs6265) have been implicated in neurodegenerative conditions. This study aimed to investigate the associations of plasma BDNF and rs6265 with cancerrelated cognitive impairment (CRCI) at the end of chemotherapy, and with persistent and delayed CRCI up to 24 months post chemotherapy, among survivors of early-stage breast cancer. Methods A multicenter, longitudinal study involving 174 breast cancer patients was conducted. CRCI was assessed using the FACT-Cog (V3) questionnaire and the CANTAB software. Plasma BDNF levels were quantified using an enzyme-linked immunosorbent assay at serial time points and genotyping was achieved using Sanger sequencing. The associations of BDNF and rs6265 with CRCI were analyzed using logistic regressions. Results A smaller magnitude of reduction in plasma BDNF between baseline and the end of chemotherapy was correlated with protection from overall subjective CRCI (OR 0.88; 95% CI 0.79–0.99). Furthermore, patients with higher plasma BDNF levels at the end of chemotherapy had lower odds of developing persistent overall subjective CRCI (OR 0.74; 95% CI 0.57–0.97) and persistent CRCI in the functional interference domain (OR 0.62; 95% CI 0.39–0.98). BDNF Met allele carriers were protected against subjective CRCI at the end of chemotherapy in the multitasking and memory domains, and against persistent subjective CRCI in the mental acuity and multitasking domains. Conclusion BDNF plasma level or rs6265 genotype information may facilitate the identification of patients at higher risk of long-term CRCI during survivorship and enable the implementation of early intervention strategies that increase BDNF levels. Keywords BDNF · rs6265 · Breast cancer · Cancer-related cognitive impairment · Survivorship Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10549-020-05807-y) contains supplementary material, which is available to authorized users. * Alexandre Chan [email protected] 1
Department of Pharmacy, National University of Singapore, Singapore, Singapore
2
Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
3
Breast Centre, K.K. Women’s and Children’s Hospital, Singapore, Singapore
4
Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore
5
Department of Clinical Pharmacy Practice, University of California, Irvine, USA
Introduction Often referred to as “chemobrain” or “chemofog”, cognitive impairment has been documented using neuropsych
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