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Associations between DNA methylation and cognitive function in early-stage hormone receptor-positive breast cancer patients

Medrxiv : the Preprint Server for Health Sciences +

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November 28, 2024

|

November 28, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Cognitive function (CF) deficits affect many breast cancer (BC) patients. This study identified DNA methylation changes in genes like CTNND2 and MLIP linked to BC-related cognitive changes, suggesting estrogen

Area Of Science

  • Genomics
  • Epigenetics
  • Neuroscience

Background

  • Cognitive function (CF) deficits are prevalent in breast cancer (BC) patients prior to adjuvant therapy.
  • Biological mechanisms underlying CF variations in BC patients are not well understood.
  • Hormone receptor-positive (HR+) early-stage BC patients exhibit poorer CF compared to healthy controls.

Purpose Of The Study

  • To identify genes and biological pathways associated with CF in postmenopausal women with early-stage HR+ BC.
  • To investigate the role of DNA methylation (DNAm) in regulating gene activity related to CF.
  • To explore potential upstream regulators of CF variations in BC survivors.

Main Methods

  • Epigenome-wide association studies (EWAS) were conducted on DNAm data from whole blood samples (n=109).
  • Analyses focused on eight CF phenotypes (seven objective, one subjective).
  • Post-EWAS functional analyses were performed to understand the significance of identified CpG sites.

Main Results

  • Two epigenome-wide significant DNAm signals were identified: cg10331779 near CTNND2 associated with processing speed and cg25906741 in MLIP associated with subjective CF.
  • Differentially methylated regions were found associated with processing speed and mental flexibility.
  • Beta-estradiol was identified as a common upstream regulator for all investigated CF phenotypes.

Conclusions

  • The study identified specific DNAm sites (cg10331779 near CTNND2, cg25906741 in MLIP) linked to processing speed and subjective CF in HR+ BC patients.
  • Estrogen signaling plays a crucial role in mediating cognitive variations in this patient group.
  • Further validation in larger cohorts is necessary to confirm these findings.