Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.
DNA methylation
biological aging
breast cancer
cognitive function
epigenetic clock
older adults
physical function
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
revised:
22
03
2023
received:
13
12
2022
accepted:
29
03
2023
pmc-release:
01
09
2024
medline:
10
8
2023
pubmed:
1
6
2023
entrez:
1
6
2023
Statut:
ppublish
Résumé
Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001-.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001-.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.
Sections du résumé
BACKGROUND
Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes.
METHODS
Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve.
RESULTS
Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001-.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001-.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors.
CONCLUSION
Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.
Identifiants
pubmed: 37259669
doi: 10.1002/cncr.34818
pmc: PMC10659047
mid: NIHMS1941984
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2741-2753Subventions
Organisme : NCI NIH HHS
ID : U54 CA137788
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA212056
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237535
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244673
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG068086
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA241337
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA051008
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA129769
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG065485
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197289
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA261793
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172119
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG068193
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028716
Pays : United States
Informations de copyright
© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
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