Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue

Abstract

Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient’s quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.

BDNF Val66Met Polymorphism Reduces the Fatigue-Like Effects of 5-Fluorouracil on Voluntary Wheel-Running Activity in Mice

“…Our main finding is that after treatment with 5FU, the fatigue-like phenotype is less prominent in the Val66Met mice than in the WT controls. This reproduces observations in clinical cancer patients, where the Met allele seems to protect against CRF ( Feng et al, 2020 ). Reproducing this in an animal model is an important step, because correlational findings in a clinical population can be difficult to interpret.…”

“…The polymorphism is most widely known for its association with higher rates of depression and mood disorders ( Notaras et al, 2015 ; Youssef et al, 2018 ), but recent studies have found a protective effect of the Val66Met polymorphism on cancer-related fatigue. Specifically, one study found a relationship between the Val66Met polymorphism and fatigue in prostate cancer patients after undergoing radiation therapy ( Feng et al, 2020 ) and other studies found a relationship between the Val66Met polymorphism and chemotherapy-related cognitive impairment in patients undergoing chemotherapy treatments for breast cancer ( Ng et al, 2015 ; Tan et al, 2019 ).…”

Plasma metabolomic profile associated with fatigue in cancer patients

“…1 However, emerging evidence suggests that the common theme among these different etiologies may be related to intrinsic genetic vulnerability combined with inflammatory triggers related to cancer or cancer treatment. 2,[7][8][9][10] Metabolomics, or metabolome profiling, is the newest addition to the -omics methodology and refers to the global identification and quantification of metabolites. 11 By definition, metabolites are small molecule metabolic products that result from chemical transformation during metabolism and, therefore, provide a real-time functional snapshot of the biochemical activity and cellular state.…”

“…Fatigue phenotypes associated with different types of cancer may arise from various pathogenic processes 1 . However, emerging evidence suggests that the common theme among these different etiologies may be related to intrinsic genetic vulnerability combined with inflammatory triggers related to cancer or cancer treatment 2,7‐10 …”

Sex and BDNF Val66Met Polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice

“…Here, we found that BDNF Met/Met mice had greater AT efficacy to promote both visual discrimination and cognitive flexibility, regardless of sex. This along with other potential advantages of the BDNF Met/Met SNP such as slower rates of cognitive decline (Barha et al, 2019b, van der Kolk et al, 2015, and protection against cancerrelated fatigue (Feng et al, 2020), may in part explain why this SNP is conserved in many populations.…”