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

Li Rebekah Feng,Josephine Liwang,Leorey N Saligan,Angela Wang,Sarah Alshawi,Jeniece M Regan,Paul Juneau

doi:10.1038/s41398-020-00990-4

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.

Highlights

Oncology patients often experience psychiatric symptoms such as cancer-related fatigue, which differs from the normal sense of “tiredness” as it cannot be resolved by rest and severely impacts their daily functioning[1]
As Val66Met has been shown to increase the risk for depression in healthy individuals[29], we examined whether this single nucleotide polymorphism (SNP) influences depression in cancer patients
Multiple lines of evidence suggest that cancer-related fatigue may be a result of unresolved inflammation stemming from a combination of genetic risk factors and inflammatory triggers including cancer[9,39]

Summary

Introduction

Oncology patients often experience psychiatric symptoms such as cancer-related fatigue, which differs from the normal sense of “tiredness” as it cannot be resolved by rest and severely impacts their daily functioning[1]. Of all cancer-related symptoms, fatigue is often the most distressing and prevalent symptom reported by up to 80% of oncology patients[1,2]. The diagnosis of cancerrelated fatigue relies entirely on self-reports with no wellestablished biomarkers[3]. The National Cancer Institute has identified cancer-related fatigue as a first-tier, high-priority research area[4,5]. The unrelenting sense of tiredness can be both persistent and severe, directly affecting the patient’s ability to perform daily tasks, resulting in helplessness and despair[6]

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