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. 2024 Dec;18(6):1851-1860.
doi: 10.1007/s11764-023-01426-w. Epub 2023 Jul 18.

Brain-Derived Neurotrophic Factor rs6265 polymorphism is associated with severe cancer-related fatigue and neuropathic pain in female cancer survivors

Taichi Goto  1 , Diane Von Ah  2 , Xiaobai Li  3 , Lichen Xiang  1 , Catherine Kwiat  1 , Christopher Nguyen  1 , Chao-Pin Hsiao  4 , Leorey N Saligan  5   6
Affiliations

Brain-Derived Neurotrophic Factor rs6265 polymorphism is associated with severe cancer-related fatigue and neuropathic pain in female cancer survivors

Taichi Goto et al. J Cancer Surviv. 2024 Dec.

Abstract

Purpose: This study examined the relationships between a single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) rs6265 and psychoneurological (PN) symptoms in female cancer survivors.

Methods: This secondary analysis examined 393 study participants. In addition to demographic variables, self-reported PN symptom scores (anxiety, bodily pain, depression, fatigue, neuropathic pain, and sleep disturbance) were collected using the Patient-Reported Outcomes Measurement Information System and 36-Item Short-Form Health Survey. Buccal swab samples were collected to obtain genotypes for BDNF rs6265 (Val/Val, Val/Met, or Met/Met). The PN symptom scores were compared across genotypes, and the relationships were examined using a regression model. We also explored correlations between different symptoms within each genotype.

Results: Participants with the Met/Met genotype reported significantly worse cancer-related fatigue and neuropathic pain, which was confirmed by rank-based regression analysis. In addition, cancer-related fatigue was correlated with other PN symptoms, particularly depression. These correlations were stronger in study participants with the Met/Met genotype than those with other genotypes.

Conclusion: Our study suggests that female cancer survivors with the Met/Met genotype of BDNF rs6265 are likely to experience worse cancer-related fatigue and neuropathic pain and that cancer-related fatigue is a good predictor of co-occurring PN symptoms in this population.

Implications for cancer survivors: Our findings advance the scientific community's understanding of cancer-related PN symptoms experienced by female cancer survivors, especially the unique role of BDNF rs6265 polymorphism in these symptoms. Our findings offer valuable insights for clinical practice that the symptom experience among female cancer survivors may vary based on BDNF genotypes.

Keywords: Cancer-related symptoms; Depression; Fatigue; Neuropathic pain; Supportive care; Val66Met.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Clustering the subjects based on their PN symptom scores and the BDNF predispositions in each cluster. A) The study participants were clustered using hierarchical clustering based on their PN symptom scores and divided into two groups exploratorily. B) The BDNF genotype frequencies were compared between the two clusters using Fisher’s exact test
Fig. 2
Fig. 2
The differences in each PN symptom per BDNF genotype. The Kruskal-Wallis test and post-hoc multiple comparisons using Wilcoxon’s rank-sum test were applied to all the statistical comparisons. BDNF, brain-derived neurotrophic factor
Fig. 3
Fig. 3
Correlations between each PN symptom. Spearman’s correlation was applied. A–C) Correlation matrices of all study participants in each genotype group. D) A scatter plot between absolute values of the fatigue score and depression score in the study participants with Met/Met genotype. E) A scatter plot between ranked values of the fatigue score and depression score in the study participants with Met/Met genotype
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