04
December
2015
|
21:48
Asia/Singapore

Gene protects against 'chemobrain'

From left: Assoc Prof Ho, Terence and Assoc Prof Chan made the discovery

An NUS group has found a gene that offers breast cancer patients protection against reduced cognitive ability brought about by chemotherapy. Besides providing an understanding of the underlying mechanisms, this discovery will help doctors identify patients at high risk of developing the side effect and take early intervention measures.

The brain-derived neurotrophic factor (BDNF) gene, which is widely expressed in the brain, is responsible for producing a protein that regulates neuronal function and development. This factor has been implicated in several neuropsychological conditions in the non-cancerous population.

However, a study led by Associate Professor Alexandre Chan and PhD candidate Terence Ng from NUS Pharmacy has uncovered a variant of the gene that protects against cognitive impairment associated with chemotherapy ' commonly termed "chemobrain or "chemofog' in patients with early-stage breast cancer.

Previous research has reported that patients with breast cancer often experience a moderate to severe degree of cognitive impairment during chemotherapy. This shows up as a spectrum of symptoms including memory loss, difficulty in decision-making and poorer multitasking ability. Preliminary evidence suggests that genetics may be a contributing factor in the increased susceptibility to the neurotoxic effects of chemotherapy. "People are convinced that it must be the drugs that cause the patients' cognitive impairment but the chances are that there are other important factors that have been overlooked, said Assoc Prof Chan.

The team's work, published in Neuro-Oncology in August 2015, was conducted from December 2011 to April 2014. The study involved 145 Asian patients from the National Cancer Centre Singapore and KK Women's and Children's Hospital who were receiving chemotherapy for early-stage breast cancer. The patients' cognitive functions, quality of life and behavioural symptoms were assessed before, during and after chemotherapy treatment. Genotyping of their blood samples was also performed in collaboration with Associate Professor Ho Han Kiat from NUS Pharmacy.

Of the 54 patients who showed cognitive impairment posttreatment, they found that carriers of a variant of the BDNF gene were less likely to experience cognitive decline, predominantly in the domains of verbal fluency and multitasking ability. This is the first time that the BDNF gene has been associated with cognitive changes in cancer patients.

The finding can provide researchers with intelligence on the mechanisms that lead to the development of these chemotherapy-induced side effects. This is important as many breast cancer survivors will return to the workforce, said Assoc Prof Chan. Productivity and employment will be issues for these people, thus knowing whether certain patients are at high-risk for cognitive impairment can benefit them if early intervention is done, he added.

The team plans to conduct further studies to validate their findings, as well as evaluate how "chemobrain is linked to other symptoms such as fatigue and anxiety. This could assist in timely and effective management strategies to avert or minimise cognitive impairment in predisposed patients. The investigators also hope to collaborate with partners in the development of therapeutics for preventing cognitive impairment in breast cancer patients.