Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the

Peh Joo Ho1,2,3, Alexis Jiaying Khng1, Benita Kiat-Tee Tan4,5,6

  • 1Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, 138672, Republic of Singapore.

PubMed
Abstract

Insights

Chemotherapy alters DNA methylation (DNAm) in breast cancer patients, affecting smell perception. This study reveals suppressed biological processes related to smell, suggesting a link between DNAm changes and sensory alterations post-treatment.

Area of Science:

  • Epigenetics
  • Genomics
  • Cancer Biology

Background:

  • Cytotoxic chemotherapy can induce changes in DNA methylation (DNAm) in breast cancer patients.
  • Understanding these epigenetic alterations is crucial for managing treatment side effects.

Purpose of the Study:

  • To investigate DNA methylation changes associated with chemotherapy in breast cancer patients.
  • To identify biological processes and pathways affected by chemotherapy-induced DNAm.

Main Methods:

  • DNAm analysis using Illumina MethylationEPIC array in 125 breast cancer patients before and after chemotherapy.
  • Linear regression models and gene set enrichment analyses (GSEA) were employed.
  • Validation in a separate cohort of 1273 treated and 872 untreated patients using blood and saliva samples.

Main Results:

  • 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy.
  • GSEA identified six suppressed biological processes related to smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, GO:0050911).
  • The KEGG pathway olfactory transduction (hsa04740) was also significantly suppressed in validation cohorts.

Conclusions:

  • Chemotherapy significantly impacts DNA methylation patterns in breast cancer patients.
  • Suppressed olfactory transduction pathways suggest chemotherapy may alter smell perception.
  • Enrichment of imprinted genes points to a potential mechanism for chemotherapy-induced sensory changes.

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