Polymorphism of BDNF genetic polymorphism and occurrence of cognitive impairment in early-stage breast cancer patients

20 Jun 2015 NUS scientists evaluated the association between the polymorphism and chemotherapy-associated cognitive impairment within an Asian breast cancer cohort. The study was recently presented at the American Society of Clinical Oncology 2015 meeting, and the lead author Mr. Terence NG (PhD Candidate, NUS Pharmacy) was awarded with the Merit Award for his winning abstract.

Currently, numerous studies have shown that breast cancer patients experience a moderate to severe degree of cognitive impairment after receiving chemotherapy. This encompasses a wide range of cognitive symptoms such as memory loss, poor concentration, difficulty in thinking, and other subtle, cognitive changes. This is a particular issue of concern to breast cancer patients who have good prognostic outcome since patients tend to return to the workforce after their active treatment, and the presence of post-chemotherapy cognitive impairment can be detrimental to their quality of life and can result in diminished functional independence. Although the exact mechanism underlying chemotherapy-associated cognitive impairment is still under investigation, preliminary evidence suggests that genetics may contribute to the increased susceptibility to the neurotoxic effects of chemotherapy. 

In this study, 145 early-stage breast cancer patients were recruited, and 54 (37%) patients experienced cognitive impairment after receiving chemotherapy. A team led by Prof Alexandre CHAN and Prof HO Han Kiat from the Department of Pharmacy in NUS found that patients with the BDNF Met/Met genotype were less likely to develop cognitive impairment. Furthermore, patients with the Met allele were less likely to experience impairment in the verbal fluency and multitasking ability domains. 

BDNF is a type of neurotrophin that is widely expressed in the brain and has been associated with neuronal repair and survival, dendritic and axonal growth, and long-term potentiation. Expressed by theBDNFgene, a single nucleotide substitution (G → A, rs6265) at nucleotide 196 in the coding sequence ofBDNFresults in an amino acid change from valine to methionine at codon position 66. This change has been linked decreased activity-dependent BDNF secretion. Given the diverse effects of BDNF in the central nervous system, theBDNFVal66Met single nucleotide polymorphism (SNP) has been the focus in genetic studies of cognitive performance and various neurodegenerative and mental disorders in the non-cancerous population. However, the relationship between the BDNF gene polymorphism and the occurrence of chemotherapy-associated cognitive impairment has yet to be evaluated.

In conclusion, the current findings provide preliminary insights into the role of BDNF SNP in the manifestation of chemotherapy-associated cognitive impairment. With further validation of these findings, a better understanding of the mechanisms underlying this adverse outcome could be achieved. In this way, effective and timely rehabilitation and management strategies can be used in susceptible patients to avert or minimize the occurrence of this adverse outcome.

Prof Alexandre Chan and his research team is currently working on a multicenter, observational study to confirm the results of this study. They are also studying the associations of other potential genes that may be associated with other toxicity syndromes, such as fatigue and anxiety, after chemotherapy among breast cancer patients.

Together with Prof Alexandre CHAN (left) and Dr CHEUNG Yin Ting (right), Terence NG (center), PhD candidate, is a winner of the Merit Award for his scientific abstract presented at the 2015 American Society of Clinical Oncology (ASCO) meeting.