Drew R Nannini, Rene Cortese, Christopher VonTungeln, Gerhard C Hildebrandt
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引用次数: 0
Abstract
Breast cancer is the most common cancer diagnosed in women and is often treated with chemotherapy. Although previous studies have demonstrated increasing biological age in patients who receive chemotherapy, evaluation of this association with DNA methylation-based markers of biological ageing may provide novel insight into the role of chemotherapy on the ageing process. We therefore sought to investigate the association between chemotherapy and markers of biological ageing as estimated from DNA methylation in women with breast cancer. DNA methylation profiling was performed on peripheral blood collected from 18 patients before and after the first cycle of chemotherapy using the Infinium HumanMethylation450 BeadChip. Six markers of biological age acceleration were estimated from DNA methylation levels. Multiple linear regression analyses were performed to evaluate the association between each metric of biological age acceleration and chemotherapy. After adjusting for chronological age and race, intrinsic epigenetic age acceleration (p = 0.041), extrinsic epigenetic age acceleration (p = 0.050), PhenoAge acceleration (p = 0.001), GrimAge acceleration (p < 0.001), and DunedinPACE (p = 0.006) were significantly higher and telomere length (p = 0.027) was significantly lower following the first cycle of chemotherapy compared to before treatment initiation. These results demonstrate greater biological ageing as estimated from DNA methylation following chemotherapy in women with breast cancer. Our findings illustrate that cytotoxic therapies may modulate the ageing process among breast cancer patients and may also have implications for age-related health conditions in cancer survivors.
期刊介绍:
Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed.
Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to):
DNA methylation
Nucleosome positioning and modification
Gene silencing
Imprinting
Nuclear reprogramming
Chromatin remodeling
Non-coding RNA
Non-histone chromosomal elements
Dosage compensation
Nuclear organization
Epigenetic therapy and diagnostics
Nutrition and environmental epigenetics
Cancer epigenetics
Neuroepigenetics