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

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.

Associations of brain‐derived neurotrophic factor rs6265 polymorphism and cognitive function in breast cancer survivors from a cross‐sectional study

“…The recruitment methods and eligibility criteria of the parent study are described in our previous paper. 24 Briefly, we enrolled BCS if they were ≥21 years old, were at ≥6 months after completing adjuvant/neo‐adjuvant therapies for breast or colorectal cancer (current Aromatase Inhibitors or Tamoxifen use at the time of enrollment was allowed), and had self‐reported CRCI. In this analysis, only female BCS with early‐stage BC (I–III) were included.…”

“…Participant characteristics, including demographic information and medical/treatment information, were obtained using an investigator‐initiated sociodemographic form. 24 The version 1.0, 8‐item short‐forms of the Patient‐Reported Outcomes Measurement Information System (PROMIS) ® Cognitive Abilities and Cognitive Concerns subscales assessed perceived CRCI. 25 The Cognitive Abilities subscales assessed CRCI by responding to statements like, “My memory has been as good as usual” and “I have been able to concentrate.” Higher scores indicate higher cognitive ability.…”

“…Data analysis was conducted using the DNASTAR Lasergene12 ® software (DNASTAR, Inc., Madison, WI, US). 24 , 31 …”

“…The detailed methods to detect rs6265 genotypes were found in our previous paper. 24,31 In summary, DNA was extracted from each sample using the QIAamp ® DNA Mini Kit (QIAGEN, Maryland, US), and then a polymerase chain reaction (PCR) experiment was performed to analyze the area containing the BDNF rs6265 SNP (GenBank dbSNP: rs6265). The primer sequences were forward 5'-AGAAG AGG AGG CTC CAAAGG-3′ and reverse 5'-ACAAG GTG GCT TGG CCTAC-3′.…”

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation

“…Similarly, research has established a connection between individuals carrying the Val allele and an increased susceptibility to chronic postsurgical pain [138], as well as a correlation with the severity of depression [139]. In addition, a recent clinical study in cancer survivors revealed that those with the Met/Met genotype of BDNF rs6265 reported significantly more severe cancer-related neuropathic pain and fatigue than those with other genotypes [140].…”