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Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer
Authors:Terence Ng  Shu Mei Teo  Hui Ling Yeo  Maung Shwe  Yan Xiang Gan  Yin Ting Cheung  Koon Mian Foo  Mooi Tai Cham  Jung Ah Lee  Yee Pin Tan  Gilbert Fan  Wei Sean Yong  Madhukumar Preetha  Wei-Jen Kiley Loh  Si-Lin Koo  Amit Jain  Guek Eng Lee  Mabel Wong  Rebecca Dent  Yoon Sim Yap  Raymond Ng  Chiea Chuen Khor  Han Kiat Ho  Alexandre Chan
Abstract:

Background

Brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment.

Methods

Overall, 145 patients receiving chemotherapy for early-stage breast cancer (mean age: 50.8 ± 8.8 y; 82.1% Chinese) were recruited. Patients'' cognitive functions were assessed longitudinally using the validated Functional Assessment of Cancer Therapy–Cognitive Function (v.3) and an objective computerized tool, Headminder. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition after adjusting for ethnicity and clinically important covariates.

Results

Of the 145 patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met genotype was associated with statistically significant lower odds of developing cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08–0.92; P = .036). The Met carriers were less likely to experience impairment in the domains of verbal fluency (OR = 0.34; 95% CI: 0.12–0.90; P = .031) and multitasking ability (OR = 0.37; 95% CI: 0.15–0.91; P = .030) compared with the Val/Val homozygote. No associations were observed between Headminder and the BDNF Val66Met polymorphism.

Conclusions

This is the first study to provide evidence that carriers of the BDNF Met allele are protected against chemotherapy-associated cognitive impairment. Further studies are required to validate the findings.
Keywords:BDNF   breast cancer   cognition   genetics   rs6265
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